Projects - Cancer

Protein

Description

Statistics

Silent information regulator 2 (Sir2)

 

Silent information regulator 2 (Sir2) can deactivate p53 (a tumour suppressor protein) which is undesirable in tumours. Sir2 inhibitors have potential as novel anti-cancer drugs.

The times for test jobs were longer than average giving more hits.



 
query: 1M2G-Q1
% jobs complete: 100.000
molecules: 39,646,275
hits: 2,479,097
time: 74:074:03:58:27
Pictures   J Posakony et al J Med Chem (2004) 47.10 p 2635-44   last updated: 12:00 on 26-JAN-06

Stromelysin

 

Stromelysin belongs to the class of Matrix MetallogProteinases (MMPs). It is a recognised anti-cancer target which is associated with tumour blood supply although finding clinically effective molecules has proven difficult.

The job times for test queries varied often giving above average numbers of hits.



 
query: 1B8Y-Q1
% jobs complete: 100.000
molecules: 39,651,357
hits: 504,911
time: 9:067:13:24:11
Pictures   R C Rizzo et al J Med Chem (2004) 47.12 p3065-74   last updated: 06:00 on 31-DEC-05

Stromelysin

 

Stromelysin belongs to the class of Matrix MetallogProteinases (MMPs). It is a recognised anti-cancer target which is associated with tumour blood supply although finding clinically effective molecules has proven difficult. This query is based on a different protein crystal structure to 1b8y-q1.

The job times for test queries took longer than average giving more hits.



 
query: 1BIW-Q1
% jobs complete: 100.000
molecules: 39,649,921
hits: 525,141
time: 17:261:22:56:20
Pictures   R C Rizzo et al J Med Chem (2004) 47.12 p3065-74   last updated: 12:00 on 19-JAN-06

Stromelysin

 

Stromelysin belongs to the class of Matrix MetallogProteinases (MMPs). It is a recognised anti-cancer target which is associated with tumour blood supply although finding clinically effective molecules has proven difficult. This query is based on a different protein crystal structure to 1b8y-q1 and 1biw-q1.

The times for test jobs were variable often giving more hits than average.



 
query: 1BQO-Q1
% jobs complete: 100.000
molecules: 39,647,310
hits: 365,178
time: 13:298:10:45:33
Pictures   R C Rizzo et al J Med Chem (2004) 47.12 p3065-74   last updated: 00:00 on 22-JAN-06

C-SRC Kinase

 

The tyrosine kinase domain of C-SRC is a known target for anti-cancer drugs. A recent news story reported the effectiveness of a Bristol-Myers Squibb drug in phase 1 clinical Leukemia trials.

We expect this queries to give average numbers of hits with typical job times.



 
query: 1BYG-Q1
% jobs complete: 100.000
molecules: 39,627,807
hits: 412,931
time: 13:196:13:26:41
Pictures   M B Lamers et al J Mol Biol (1999) 285.2 p713-25   last updated: 06:07 on 30-MAR-05

Catalytic Domain of Cell Cycle Control Phosphatase (Cdc25A)

 

Cdc25A plays an important role in the cell cycle interacting with Cdk2. Inhibition of the cell cycle causes cell death. It is anticipated that because Cdc25A is present in increased concentrations in cancer cells that sufficient selectivity might be achieved to stop tumour growth.

This catalytic site is unusually shallow and we are not expecting a high hit rate.



 
query: 1C25-Q2
% jobs complete: 100.000
molecules: 39,878,350
hits: 5,805
time: 9:079:01:36:56
Pictures   E B Fauman et al, Cell (1998) Vol 93 p617-625   last updated: 12:12 on 13-APR-04

E6AP ubiquitin-protein ligase

 

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer. Inhibiting this interaction may be therapeutically useful preventing and treating cervical cancer.

Test jobs ran faster than average jobs giving few hits.



 
query: 1C4Z-Q1
% jobs complete: 100.000
molecules: 39,649,484
hits: 38,789
time: 2:282:15:45:06
Pictures   L Huang et al Science (1999) Nov 286 p1321-6   last updated: 00:11 on 16-SEP-05

Farnesyltransferase Protein

 

Farnesyltransferase Protein (FTP) activates RAS by binding to it. As a result of earlier queries for the same protein (1d8d-q2) we have been able to generate a revised query which we believe is more likely to find molecules which show activity when tested in the laboratory.



 
query: 1D8D-Q3
% jobs complete: 100.000
molecules: 39,878,211
hits: 58,740
time: 12:111:18:20:04
Pictures   S B Long, P J Casey, L S Beese Structure (London) 8 p209 (2000)   last updated: 18:10 on 27-FEB-04

Phosphatidylinositol 3 Kinase

 

Phosphatidylinositol 3 Kinase (PI3K) regulation of the Akt/PKB pathway is essential for cell survival. Inhibition of PI3K leads to apoptosis (cell death) as a consequence Akt/PKB not phosphorylating proteins including Bad, transcription factors, caspase-9 amd ASK-1. There is reason for thinking that cancer cells would be selectively killed by a PI3K inhibitor.



 
query: 1E7U-Q1
% jobs complete: 100.000
molecules: 510,650,313
hits: 6,535,525
time: 332:134:20:51:11
Pictures   E H Walker et al (2000) Mol Cell Biol 6 p909   last updated: 06:05 on 05-MAY-04

Matriptase

 

Matriptase belongs to the serine protease family of proteins. It has recently been identified as a cancer target.

The job times for test queries took longer than average giving more hits.



 
query: 1EAW-Q1
% jobs complete: 100.000
molecules: 39,647,696
hits: 682,994
time: 39:256:09:50:01
Pictures   R Friedrich and W Bode J Biol Chem (2001) 277 p2160   last updated: 18:00 on 25-JAN-06

Matriptase

 

Matriptase belongs to the serine protease family of proteins. It has recently been identified as a cancer target. This query is based on a different crystal structure to 1eaw-q1.

The job times and number of hits for test queries varied.



 
query: 1EAX-Q1
% jobs complete: 100.000
molecules: 39,647,952
hits: 52,938
time: 10:349:07:04:49
Pictures   R Friedrich and W Bode J Biol Chem (2001) 277 p2160   last updated: 00:00 on 20-JAN-06

Fibroblast growth factor receptor-2

 

Fibroblast growth factor receptor-2 (FGFr-2) is understood to play a role in signalling cell growth and is a recognised cancer therapy target.

For this query the times taken by test jobs varied giving typical numbes of hits.



 
query: 1EV2-Q2
% jobs complete: 100.000
molecules: 510,439,643
hits: 1,978,370
time: 273:159:00:12:08
Pictures   A N Plotnikov et al Cell (2000) 101.4 p413-24   last updated: 00:00 on 21-JAN-06

Fibroblast growth factor receptor-1

 

Fibroblast growth factor receptor-1 (FGFr-1) is understood to play a role in signalling cell growth and is a recognised cancer therapy target.

For this query the times taken by test jobs varied giving fewer hits than usual.



 
query: 1EVT-Q1
% jobs complete: 100.000
molecules: 39,643,984
hits: 64,465
time: 5:082:18:23:45
Pictures   A N Plotnikov et al Cell (2000) 101.4 p413-24   last updated: 12:05 on 28-OCT-05

Fibroblast growth factor receptor-1

 

Fibroblast growth factor receptor-1 (FGFr-1) is understood to play a role in signalling blood vessel development in which there has been renewed interest recently. It is recognised that VEFGr plays a key role in blood vessel development and it is suggested that inhibition of FGFr-1 may be an alternative to inhibiting VEGFr with fewer side-effects.

This query has been prepared for use with THINK 1.23 and in the first instance will only be available to members participating in the beta test.



 
query: 1FGI-Q1
% jobs complete: 100.000
molecules: 510,661,562
hits: 4,435,948
time: 55:208:02:25:17
Pictures   M Mohammadi et al EMBO J (1998) 17 p5896-5904   last updated: 12:24 on 06-DEC-04

Vascular Endothelial Growth Factor Receptor (VEGFr)

 

VEGF stimulates the growth of blood vessels. The uncontrolled growth of cancer cells is legendary. But this sort of growth requires a lot of blood flow to the cell area. If the blood vessel growth can be restrained, then, in theory, so can growth of the tumour.

We extended the numbers of molecules to be processed to approximately 0.5 billion on 11-Sep-03.



 
query: 1FLT-Q4
% jobs complete: 100.000
molecules: 510,697,025
hits: 5,961,258
time: 120:116:06:45:41
Pictures   C Wiesmann et al (1997) Cell Vol 91 p695   last updated: 00:06 on 04-MAY-04

BRAF: ADP-Binding transport protein

 

ADP and ATP transport play a critical role in cell biochemistry. Professor Paul Workman (Director of Cancer Research UK) recently commented that BRAF was was an exciting target for which it may be possible to design selective inhibitors for very specific cancers such as melanomas because mutant forms of BRAF occur (see DDT 2003, Vol 8.17 p775-777).



 
query: 1G6H-Q1
% jobs complete: 100.000
molecules: 510,706,356
hits: 590,767
time: 57:353:10:49:56
Pictures   N Karpowich et al Structure (2001) Vol 9 p 571   last updated: 00:09 on 10-SEP-04

Urokinase plasminogen activator (uPA)

 

Urokinase plasminogen activator (uPA) is a member of the serine protease family of proteins. It is believed that this enzymes plays an important role transporting cancer around the body. If this enzyme is inhibited secondary cancers which can often be fatal are unlikely to develop. This query is based on a different crystal structure to 1sqo-q1 and 1vj9-q2.

Jobs for this query are processed slightly faster than typical jobs giving the usual number of hits.



 
query: 1GI8-Q1
% jobs complete: 100.000
molecules: 510,443,985
hits: 4,491,043
time: 97:075:18:24:48
Pictures   A Schweinitz et al J Biol Chem (2004) 279 p33613   last updated: 06:00 on 26-JAN-06

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. This query is derived from a mutant AR which is associated with cancer.

This query gives above average numbers of hits with job times often longer than typical.



 
query: 1GS4-Q1
% jobs complete: 100.000
molecules: 510,447,098
hits: 6,752,753
time: 395:201:06:37:25
Pictures   P M Matias et al J Med Chem (2002) 45 p1439   last updated: 06:00 on 26-JAN-06

Phosphatidylinositol 3 Kinase (alpha)

 

Phosphatidylinositol 3 Kinase (PI3K) regulation of the Akt/PKB pathway is essential for cell survival. Inhibition of PI3K leads to apoptosis (cell death) as a consequence Akt/PKB not phosphorylating proteins including Bad, transcription factors, caspase-9 amd ASK-1. There is reason for thinking that cancer cells would be selectively killed by a PI3K inhibitor.

The time taken and numbers of hits varied widely in our test jobs.



 
query: 1H9O-Q1
% jobs complete: 100.000
molecules: 39,726,395
hits: 430,454
time: 42:271:16:12:50
Pictures   R A Pauptit et al (2001) Acta Cryst D57 p1397   last updated: 06:14 on 08-DEC-04

X-linked Inhibitor of Apoptosis Protein (XIAP)

 

Inhibitor of Apoptosis proteins are often present in exceptionally high quantities in cancer tissues. It is believed that molecules which bind to X-linked Inhibitor of Apoptosis Protein (XIAP) induce cell death by freeing caspases.

The job times for test queries varied with most giving typical numbers of hits.



 
query: 1I4O-Q1
% jobs complete: 100.000
molecules: 39,645,015
hits: 10,752
time: 1:055:06:38:30
Pictures   K Thorsten et al J Med Chem (2004) 47.18 p4417-26   last updated: 00:00 on 12-JAN-06

Transcription Factor 4 (TCF4)

 

Transcription Factor 4 (TCF4) is a known to interact with beta-catenin in several different ways. It is a recognised anti-cancer target although side-effects and selectivity are likely to be problematic.

The job times for test queries where typical often giving more hits.



 
query: 1JD4-Q1
% jobs complete: 100.000
molecules: 39,648,638
hits: 391,663
time: 8:360:12:44:02
Pictures   J W Wu et al Mol Cell (2001) 8 p95-104   last updated: 06:03 on 23-JAN-06

Topoisomerase I

 

Topoisomerase plays a role in DNA transcription and replication. It is understood that molecules which interfere with this process have potential as in cancer therapy (although side-effects may be a concern).

This query gave fewer hits than typical jobs in less time.



 
query: 1K4T-Q3
% jobs complete: 100.000
molecules: 39,627,838
hits: 76,243
time: 4:046:02:26:39
Pictures   B L Staker et al, Proc Natl Acad Sci (2002) 99.24 p15387-93   last updated: 12:12 on 17-MAY-05

C-SRC tyrosine kinase

 

Tyrosine kinases occur widely in human tissues. Achieving selectivity is important to avoid side-effects especially if a drug is to be taken for a long period of time. C-SRC tyrosine kinase is a recognised anti-cancer drug target.

The job times for test queries took longer than average giving more hits.



 
query: 1KSW-Q1
% jobs complete: 100.000
molecules: 39,650,404
hits: 131,405
time: 7:208:09:00:16
Pictures   L A Witucki et al Chem Biol (2002) 9.1 p25-33   last updated: 12:01 on 22-DEC-05

Estrogen-a receptor

 

The estrogen receptor belongs to the family of Nuclear Receptors which trigger protein synthesis (via DNA transcription). Hormones bind to the ligand binding domain facilitating the DNA to interact with another domain. Inhibiting the Estrogen ligand binding domain is thought to have potential in cancer therapy. This query is based on a different crystal structure to 1sj0-q1 and 1uom-q1.

This query gave more hits than typical jobs with jobs taking longer than average.



 
query: 1L2I-Q1
% jobs complete: 100.000
molecules: 39,649,625
hits: 284,325
time: 38:207:23:16:55
Pictures   S Kim et al, J Med Chem (2004) 47.9 p2171-5   last updated: 06:00 on 12-JAN-06

Hypoxia-inducible factor (HIF-1)

 

HIF-1 plays a central role to increase oxygen supply to tumours by directing the production of proteins that promote increased blood vessels. It is believed that the mode of action uses transcription coactivators such as p300, CBP or SRC-1. In this query we are attempting to find molecules which inhibit the HIF-1 p300 interaction.



 
query: 1L3E-Q1
% jobs complete: 100.000
molecules: 510,665,033
hits: 2,104,865
time: 95:104:18:01:32
Pictures   S J Freedman et al PNAS (2002) 99.8 p5367-5372   last updated: 12:17 on 13-DEC-04

C-SRC tyrosine kinase

 

Tyrosine kinases occur widely in human tissues. Achieving selectivity is important to avoid side-effects especially if a drug is to be taken for a long period of time. C-SRC tyrosine kinase is a recognised anti-cancer drug target.

The job times for test queries took less time than average giving few hits.



 
query: 1LCJ-Q1
% jobs complete: 100.000
molecules: 39,650,372
hits: 14,930
time: 3:162:23:36:16
Pictures   L A Witucki et al Chem Biol (2002) 9.1 p25-33   last updated: 12:00 on 20-JAN-06

b-Catenin

 

b-Catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. It has been suggested that for some cancers inhibiting b-Catenin has therapeutic potential.

The time taken and numbers of hits varied significantly in test jobs.



 
query: 1LUJ-Q1
% jobs complete: 100.000
molecules: 39,627,322
hits: 108,171
time: 10:148:19:04:28
Pictures   T A Graham et al Mol Cell (2002) 10.3 p563-71   last updated: 18:28 on 07-AUG-05

Epidermal growth factor receptor

 

Two-thirds of solid tumors arise from epithelial tissues, and studies suggest that EGFR inhibitors can stabilize or shrink many of these malignancies. It is conceivable that EGFR inhibitors could beneficial in therapies for cancers of the lung, pancreas, head and neck, breast, prostate, colon, stomach, ovaries, and brain. However, the initial inhibitors in clinicals trials where less successful than expected. In this project, we hope to find more effective molecules.



 
query: 1M17-Q2
% jobs complete: 100.000
molecules: 39,878,367
hits: 15,342
time: 3:004:06:07:50
Pictures   J Stamos, M X Sliwkowski and C Eigenbrot J Biol Chem (2002) Vol 277 p46265   last updated: 06:27 on 01-OCT-03

Casein Kinase 2

 

Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. Casein Kinase 2 (CK2) is implicated in a variety of cellular functions and misfunctions. In tumours it is often present in abnormally higher concentrations, suggesting that inhibition may be of therapeutic value.

In tests, jobs took longer than typical jobs and gave more hits than usual.



 
query: 1M2R-Q1
% jobs complete: 100.000
molecules: 510,388,589
hits: 10,510,309
time: 470:127:10:55:13
Pictures   E De Moliner et al J Biol Chem (2003) 278.3 p1831-6   last updated: 12:00 on 25-JAN-06

Nuclear Matrix Protein (NuMA)

 

It has been suggested by scientists at the University of Pittsburgh that Nuclear Matrix Protein (NuMA) might be a valuable drug target for cancer therapy. Inhibiting NuMA has the potential to selectively stop cancerous cells from multiplying by the cell division process.

These jobs take longer than typical jobs giving more hits than usual.



 
query: 1MP1-Q1
% jobs complete: 100.000
molecules: 39,627,511
hits: 259,482
time: 23:052:16:37:03
Pictures   N J Quintyne et al, Science (2005) 307 p127-9   last updated: 12:12 on 04-JUL-05

AKT-2

 

AKT-2 belongs to the serine/threonine kinase family. Its activity has been implicated in diseases that involve inappropriate cell survival including cancer when it is present in abnormally high levels. This query is unusual because it is based on a crystal structure which is believed to exhibit the protein in an inactive state.

In tests, jobs took less time than typical jobs and gave fewer hits than usual.



 
query: 1MRY-Q1
% jobs complete: 100.000
molecules: 39,627,627
hits: 15,196
time: 2:229:01:02:50
Pictures   X Huang et al Structure (2003) 11.1 p21-30   last updated: 12:07 on 09-JUL-05

MYC-MAX transcription factor

 

MYC-MAX transcription factor determines whether a cell will divide and proliferate. Deregulation of MYC has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. An effective transcription inhibitor may have therapeutic potential in cancer.

In test jobs, the time taken was typical with fewer hits than usual.



 
query: 1NKP-Q2
% jobs complete: 100.000
molecules: 39,627,510
hits: 46,137
time: 11:184:22:51:51
Pictures   S K Nair and S K Burley Cell (2003) 112.2 p193-205   last updated: 00:11 on 07-AUG-05

MYC-MAX transcription factor

 

MYC-MAX transcription factor determines whether a cell will divide and proliferate. Deregulation of MYC has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. An effective transcription inhibitor may have therapeutic potential in cancer. This query is a revision of 1nkp-q2.

In test jobs, the time taken was typical with fewer hits than usual but more than 1nkp-q2.



 
query: 1NKP-Q3
% jobs complete: 100.000
molecules: 39,627,924
hits: 37,683
time: 4:282:17:48:32
Pictures   S K Nair and S K Burley Cell (2003) 112.2 p193-205   last updated: 18:42 on 04-AUG-05

Chk1

 

Chk1 is a serine-threonine kinase that plays an important role in DNA damage response by suspending cell division. It is believed that inhibiting Chk1 can lead to cell death by allowing the cell to accumulate faulty proteins from the damaged DNA.



 
query: 1NVS-Q1
% jobs complete: 100.000
molecules: 39,874,039
hits: 352,166
time: 5:068:19:31:55
Pictures   B Zhao et al, J Bio Chem (2002) 227.48 p46609-15   last updated: 18:24 on 09-NOV-04

C-SRC tyrosine kinase

 

Tyrosine kinases occur widely in human tissues. Achieving selectivity is important to avoid side-effects especially if a drug is to be taken for a long period of time. C-SRC tyrosine kinase is a recognised anti-cancer drug target. This query is based on a different crystal structure to 1lcj-q1.

The job times for test queries varied sometimes taking longer average jobs and giving more hits.



 
query: 1O4P-Q1
% jobs complete: 100.000
molecules: 39,645,191
hits: 176,016
time: 21:033:15:16:07
Pictures   L A Witucki et al Chem Biol (2002) 9.1 p25-33   last updated: 12:00 on 20-JAN-06

Protein Kinase B (AKT-2)

 

Protein Kinase B (AKT-2) appears to play a role in certain cancer therapies (including breast cancer) by protecting cancer cells from chemotherapy induced death. The actual mechanism is complicated: indirect inhibition of JNK/p38 apoptosis - see other queries and University of South Florida research. AKT-2 inhibitors have the potential to improve the effectiveness of other anti-cancer drugs.

The jobs for this query often take less time than typical jobs the usual number of hits.



 
query: 1O6K-Q1
% jobs complete: 100.000
molecules: 39,627,631
hits: 182,814
time: 3:004:16:10:02
Pictures   J Yang et al Nat Struct Biol (2002) 9 p940   last updated: 18:14 on 10-APR-05

Receptor Protein Tyrosine Phosphatase a

 

Receptor Protein Tyrosine Phosphatase a (RPTP-a) was suggested as a possible target for anti-cancer drugs in Drug Discovery Today (2005) 10.10 p735. However, as the family of vphosphatase is quite large, selectivity is likely to be important.

Test jobs ran slower than average jobs giving more hits.



 
query: 1P15-Q1
% jobs complete: 100.000
molecules: 39,649,751
hits: 151,068
time: 7:113:14:39:54
Pictures   E D Sonnenburg et al Biochemistry (2003) 42.26 p7904-14   last updated: 00:10 on 07-NOV-05

Mitogen Activated Protein (MAP) Kinase

 

Mitogen Activated Protein (MAP) Kinases are signaling proteins that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. The MAP kinase this query is based on is known as ERK2 (extracellular-signal-regulated kinase 2) and plays a role in cellular differentiation or proliferation. This query is based on a different crystal structure to 3erk-q1 and 4erk-q1.

For this query the times taken by test jobs and numbers of hits were above average.



 
query: 1PME-Q1
% jobs complete: 100.000
molecules: 39,649,990
hits: 458,669
time: 29:351:07:13:33
Pictures   Z Wang et al Structure (1998) 6.9 p1117-28   last updated: 06:04 on 01-NOV-05

BCL-XL

 

BCL-XL plays a role which is not fully understood in stimulating cell death. It is a recognised target for anti-cancer drugs.

The times for test jobs of this query were variable but usually taking less time than average jobs and often giving more hits than normal.



 
query: 1PQ1-Q2
% jobs complete: 100.000
molecules: 39,639,252
hits: 148,058
time: 6:140:10:10:29
Pictures   X Liu et al Immunity (2003) 19.3 p341-52   last updated: 12:00 on 11-JAN-06

BCL-XL

 

BCL-XL plays a role which is not fully understood in stimulating cell death. It is a recognised target for anti-cancer drugs. This query targets a different site on the same protein as 1pq1-q2.

The times for test jobs of this query were variable but usually taking less time than average jobs and often giving few hits.



 
query: 1PQ1-Q3
% jobs complete: 100.000
molecules: 39,651,664
hits: 19,158
time: 5:110:03:03:36
Pictures   X Liu et al Immunity (2003) 19.3 p341-52   last updated: 18:00 on 22-JAN-06

DJ-1/RS

 

DJ-1 is a protein involved in multiple physiological processes, including cancer, Parkinson's disease, and male fertility. The details of how DJ-1 functions are not known. In cancer it is believed that it reduces the levels of the PTEN tumour suppressor which enables cell growth.

We expect most jobs for this query to take less time than usual giving fewer hits.



 
query: 1Q2U-Q1
% jobs complete: 100.000
molecules: 39,646,069
hits: 35,069
time: 2:292:04:12:35
Pictures   Q Huai et al FEBS Lett (2003) 549 p171-5.   last updated: 18:06 on 15-SEP-05

cAMP-dependent Protein Kinase (PKA)

 

cAMP-dependent Protein Kinase (PKA) is a recognised anti-cancer target - see DDT (2005) 10.12 p839-846. It has previously been considered as primarily an anti-inflammatory target.

Job times for this query took longer and gave more hits than typical queries.



 
query: 1Q8T-Q1
% jobs complete: 100.000
molecules: 39,645,455
hits: 267,186
time: 17:064:13:58:28
Pictures   C Breitenlechner et al Structure (2003) 11 p1595   last updated: 12:00 on 20-JAN-06

Catalytic Domain of Cell Cycle Control Phosphatase (Cdc25B)

 

Cdc25B plays a more specific role than Cdc25A in the cell cycle interacting with Cdk2. Inhibition of the cell cycle causes cell death. It is a recognised cancer target and has been observed at increased levels in several human breast cancers.

We are anticipating large numbers of hits and slightly long job times.



 
query: 1QB0-Q1
% jobs complete: 100.000
molecules: 39,860,371
hits: 1,925,725
time: 98:145:21:31:42
Pictures   R A Reynolds et al, J Mol Biol (1999) Vol 293 p559-568   last updated: 00:18 on 30-NOV-04

Methionine aminopeptidase II (MetAP 2)

 

Inhibiting this enzyme is believed to help suppress the development of blood vessels for tumours. To be useful therapeutically, an inhibitor should selectively inhibit MetAP2 without inhibiting MetAP1.

Job times for this query do vary but the average time and number of hits is typical.



 
query: 1QZY-Q1
% jobs complete: 100.000
molecules: 510,395,537
hits: 1,921,098
time: 116:292:19:32:58
Pictures   G S Sheppard et al Bioorg Med Chem Lett (2004) 14.4 p865-8   last updated: 00:08 on 08-AUG-05

E2 domain of Human Papillomavirus Virus type 11 (HPV-11)

 

Genital Human Papillomavirus Virus type 11 (HPV-11) is carcinogenic and are associated with most cases of cervical cancer. Inhibiting the E2 transactivation domain of the virus might be expected to inhibit the spread of the virus and consequently the risk of causing cancer.

We expect this queries to give average numbers of hits with average job times.



 
query: 1R6N-Q1
% jobs complete: 100.000
molecules: 39,618,433
hits: 69,656
time: 3:110:16:30:16
Pictures   Y Wang et al, J Biol Chem (2004) 279 p 6976   last updated: 06:06 on 08-APR-05

E2 domain of Human Papillomavirus Virus type 11 (HPV-11)

 

Genital Human Papillomavirus Virus type 11 (HPV-11) is carcinogenic and are associated with most cases of cervical cancer. Inhibiting the E2 transactivation domain of the virus might be expected to inhibit the spread of the virus and consequently the risk of causing cancer. This query targets an alternative binding site to 1r6n-q1.

We expect this queries to give few hits and have typical job times.



 
query: 1R6N-Q3
% jobs complete: 100.000
molecules: 39,627,462
hits: 2,281
time: 2:316:06:36:15
Pictures   Y Wang et al, J Biol Chem (2004) 279 p 6976   last updated: 12:09 on 02-JUL-05

Human Double Minute 2 (HDM2) with inhibitor

 

The p53 tumour suppressor protein regulates cell proliferation in cancer tumours. A small drug molecule which can binding to HDM2 would offer a novel cancer therpy with the potential to enable p53 to stop growth or kill the cancer cells. This query has some similarities to 1ycr-q3 but is based on a more recent crystal structure which includes an inhibitor.



 
query: 1RV1-Q2
% jobs complete: 100.000
molecules: 510,379,315
hits: 10,159,522
time: 330:023:20:13:16
Pictures   L Y Vassilev et al Science (2004) 303 p844   last updated: 06:09 on 04-AUG-05

Fibroblast growth factor receptor-3

 

Fibroblast growth factor receptor-3 (FGFr-3) is understood to play a role in signalling cell growth and is a recognised cancer therapy target.

Test jobs for this query took less time than average jobs giving slightly above average numbers of hits.



 
query: 1RY7-Q2
% jobs complete: 100.000
molecules: 39,650,685
hits: 232,363
time: 5:132:06:15:04
Pictures   S K Olsen et al Proc Nat Acad Sci (2004) 101 p935   last updated: 00:11 on 17-SEP-05

ErbB2

 

In cancer cells, the ErbB2 receptor tyrosine kinase is sometimes present in higher concentrations than normal. ErbB2 is an important signally protein and stimulation leads to growth of the tumour. It may therefore be an important anti-cancer drug target.

We expect this queries to give few hits with job times slightly less than average.



 
query: 1S78-Q1
% jobs complete: 100.000
molecules: 39,627,453
hits: 8,365
time: 2:141:02:27:59
Pictures   M C Franklin et al, Cancer Cell (2004), 5.4 p317-28   last updated: 06:11 on 10-JUN-05

Mitogen-Activated Protein Kinase 2 (MEK2)

 

Mitogen-Activated Protein Kinase 2 (MEK2) is a tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. This growth pathway is activated in many cancers and inhibiting it might be a useful cancer therapy for certain tumours.

In test jobs the time taken varied but was often less than typical jobs giving at least typical numbers of hits.



 
query: 1S9I-Q1
% jobs complete: 100.000
molecules: 39,627,629
hits: 109,176
time: 7:132:08:39:16
Pictures   J F Ohren et al Nat Struct Mol Biol (2004) 11.12 p1192-7   last updated: 12:11 on 18-JUN-05

Mitogen-Activated Protein Kinase 1 (MEK1)

 

Mitogen-Activated Protein Kinase 1 (MEK1) is a tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. This growth pathway is activated in many cancers and inhibiting it might be a useful cancer therapy for certain tumours.

In test jobs the time taken varied but was often longer than 1S9I-Q1 (MEK1) giving at least typical numbers of hits.



 
query: 1S9J-Q1
% jobs complete: 100.000
molecules: 510,424,593
hits: 2,511,877
time: 59:043:15:22:14
Pictures   J F Ohren et al Nat Struct Mol Biol (2004) 11.12 p1192-7   last updated: 12:00 on 04-JAN-06

Estrogen receptor

 

The estrogen receptor belongs to the family of Nuclear Receptors which trigger protein synthesis (via DNA transcription). Hormones bind to the ligand binding domain facilitating the DNA to interact with another domain. Inhibiting the Estrogen ligand binding domain is thought to have potential in cancer therapy.

This query gave more hits than typical jobs with jobs taking longer than average.



 
query: 1SJ0-Q1
% jobs complete: 100.000
molecules: 39,627,572
hits: 236,902
time: 21:219:16:15:58
Pictures   S Kim et al, J Med Chem (2004) 47.9 p2171-5   last updated: 00:08 on 06-AUG-05

Urokinase plasminogen activator (uPA)

 

Urokinase plasminogen activator (uPA) is a member of the serine protease family of proteins. It is believed that this enzymes plays an important role transporting cancer around the body. If this enzyme is inhibited secondary cancers which can often be fatal are unlikely to develop.

Jobs for this query are processed slightly faster than typical jobs giving the usual number of hits.



 
query: 1SQO-Q1
% jobs complete: 100.000
molecules: 510,423,887
hits: 3,668,750
time: 77:293:17:29:35
Pictures   M D Wendt et al, Bioorg Med Chem Lett (2004) 14.12 p3063-8   last updated: 18:36 on 05-AUG-05

Breast Cancer Type 1 Susceptibility Protein (BRCA1)

 

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is thought to play a role in breast and ovarian cancers. It is known that mutations play a role but it is not clear whether inhibiting BRCA1 will be therapeutically useful.

We expect jobs for this query to give typical numbers of hits in less than average times.



 
query: 1T15-Q1
% jobs complete: 100.000
molecules: 39,645,845
hits: 221,164
time: 3:356:07:31:02
Pictures   E N Shiozaki et al Mol Cell (2004) 14.3 p405-12.   last updated: 18:06 on 11-AUG-05

Breast Cancer Type 1 Susceptibility Protein (BRCA1)

 

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is thought to play a role in breast and ovarian cancers. It is known that mutations play a role but it is not clear whether inhibiting BRCA1 will be therapeutically useful. This is query is based on a different crystal structure to 1t15-q1.

We expect jobs for this query to give typical numbers of hits in less than average times.



 
query: 1T29-Q2
% jobs complete: 100.000
molecules: 39,649,882
hits: 58,568
time: 12:014:11:48:50
Pictures   E N Shiozaki et al Mol Cell (2004) 14.3 p405-12.   last updated: 06:06 on 22-SEP-05

c-Kit Tyrosine Kinase

 

c-Kit Tyrosine Kinase is a transmembrane protein that initiates cell growth signalling. Mutations of c-Kit can result in over-stimulation when the natural regulation fails. This has been observed in gastrointestinal stromal tumors, germ cell tumors, mast cell and myeloid leukemias, and in mastocytosis. An inhibitor might be useful therapeutically for a range of different cancers.

We expect jobs for this query to give than typical numbers of hits faster than recent queries.



 
query: 1T46-Q1
% jobs complete: 100.000
molecules: 39,647,042
hits: 140,289
time: 6:138:01:03:37
Pictures   C D Mol et al, J Biol Chem (2004) 279.30 p31655-63   last updated: 00:04 on 15-DEC-05

Histone deacetylase (HDAC)

 

Histone deacetylases (HDACs) are essential to removing of acetyl groups from histone proteins which in turn have a pivotal role in gene expression. It has been suggested that HDAC inhibitors may be useful in the treatment of several types of cancers.

These are based on a different crystal structure thant 1w22-q1 and 1t69-q1 of the same protein. They give fewer than typical numbers of hits in typical jobs times.



 
query: 1T67-Q2
% jobs complete: 100.000
molecules: 39,627,375
hits: 39,619
time: 6:247:01:09:29
Pictures   J R Somoza et al, Structure (2004) 12 p1325   last updated: 00:10 on 11-JUN-05

Histone deacetylase (HDAC)

 

Histone deacetylases (HDACs) are essential to removing of acetyl groups from histone proteins which in turn have a pivotal role in gene expression. It has been suggested that HDAC inhibitors may be useful in the treatment of several types of cancers.

These jobs show some variation in time taken. Those with few hits complete relatively quickly.



 
query: 1T69-Q1
% jobs complete: 100.000
molecules: 39,627,489
hits: 158,498
time: 4:022:07:22:21
Pictures   J R Somoza et al, Structure (2004) 12.7 p1325-34   last updated: 00:13 on 03-MAR-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the last of the current series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs a little slower than some earlier targets in this series.



 
query: 1T73-Q1
% jobs complete: 100.000
molecules: 39,627,692
hits: 399,791
time: 29:227:03:26:41
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 18:17 on 01-MAR-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the seventh of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs a little slower than some earlier targets in this series.



 
query: 1T74-Q1
% jobs complete: 100.000
molecules: 39,627,512
hits: 230,373
time: 17:215:23:53:25
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 18:14 on 04-MAR-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the sixth of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs a little slower than some earlier targets in this series.



 
query: 1T76-Q1
% jobs complete: 100.000
molecules: 510,392,712
hits: 1,600,630
time: 285:253:14:46:25
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 18:12 on 03-AUG-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the fourth of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs completing in a few hours on a typical PC.



 
query: 1T79-Q1
% jobs complete: 100.000
molecules: 39,627,827
hits: 208,379
time: 12:077:19:00:01
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 00:09 on 03-FEB-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the fifth of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs completing in a few hours on a typical PC.



 
query: 1T7F-Q1
% jobs complete: 100.000
molecules: 39,627,559
hits: 193,088
time: 10:019:17:17:42
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 18:09 on 21-JAN-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the second of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs completing in a few hours on a typical PC.



 
query: 1T7M-Q1
% jobs complete: 100.000
molecules: 39,627,755
hits: 217,881
time: 14:200:21:39:26
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 06:13 on 03-MAR-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the third of a series which explores how this flexibility affects which molecules can bind and the influence of certain cofactors.

This query requires THINK 1.25b and gives average numbers of hits with many jobs completing in a few hours on a typical PC.



 
query: 1T7R-Q1
% jobs complete: 100.000
molecules: 39,627,287
hits: 221,423
time: 10:226:10:54:22
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 14:04 on 12-FEB-05

Androgen receptor (AR)

 

5-adihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. The binding site is known to show some flexibility and this query is the first of a series which explores how this flexibility affects which molecules can bind.

This query requires THINK 1.25b and gives average numbers of hits with many jobs completing in a few hours on a typical PC.



 
query: 1T7T-Q1
% jobs complete: 100.000
molecules: 39,627,592
hits: 181,062
time: 8:188:03:47:05
Pictures   E Hur et al, Plos Biol (2004) v2 p E274   last updated: 18:09 on 25-JAN-05

zap-70 (Syk-related) Tyrosine Kinase

 

Many Tyrosine Kinases including SYK are inhibited by some anti-cancer drugs. Tyrosine Kinases are also associated with rheumatoid arthritis, inflammation and immunological responses. A lack of selectivity might cause undesirable side-effects and prohibit long term use as preventative treatment.

We expect jobs for this query to take longer than typical jobs giving more hits.



 
query: 1U59-Q1
% jobs complete: 100.000
molecules: 39,649,053
hits: 156,965
time: 15:134:20:11:54
Pictures   L Jin et al J Biol Chem (2004) 279 p42818   last updated: 12:07 on 23-SEP-05

Estrogen-a receptor

 

The estrogen receptor belongs to the family of Nuclear Receptors which trigger protein synthesis (via DNA transcription). Hormones bind to the ligand binding domain facilitating the DNA to interact with another domain. Inhibiting the Estrogen ligand binding domain is thought to have potential in cancer therapy. This query is based on a different crystal structure to 1sj0-q1.

This query gave more hits than typical jobs with jobs taking longer than average.



 
query: 1UOM-Q1
% jobs complete: 100.000
molecules: 39,647,719
hits: 192,504
time: 13:063:04:30:41
Pictures   S Kim et al, J Med Chem (2004) 47.9 p2171-5   last updated: 12:00 on 23-JAN-06

Thymidine Phosphorylase (TP)

 

TP is an angiogenic growth factor and a target for anticancer design. The structure of TP has been reported to be identical to Platelet-Derived Endothelial Cell Growth Factor (PD-ECGF) which has been implicated in a variety of angiogenic effects promoting cell proliferation in solid tumours.

This query runs significantly faster with 1.24b which is currently in beta test.



 
query: 1UOU-Q1
% jobs complete: 100.000
molecules: 510,623,270
hits: 2,916,527
time: 177:339:04:52:49
Pictures   I J Stratford et al J Med Chem (2003) 46 p207-209   last updated: 00:13 on 13-DEC-04

Phosphoinositide dependent protein kinase (PDK1)

 

Phosphoinositide dependent protein kinase (PDK1) plays a critical role signalling cell growth activating at least 24 different proteins. It is therefore an attractive potential drug target for cancer therapy.

Test jobs for this query gave slightly above average numbers of hits in longer than typical job times.



 
query: 1UU3-Q1
% jobs complete: 100.000
molecules: 510,426,486
hits: 7,456,489
time: 408:233:03:09:36
Pictures   D Komander et al Structure (2004) 12 p215   last updated: 06:11 on 08-AUG-05

BRAF

 

This query is based on a new crystal structure of BRAF which included a potential anti-cancer drug which holds the protein in its inactive form. We are optimistic that this query will provide more interesting results than the earlier 1G6H-Q1 BRAF query.

These jobs generate above average number of hits and take slightly longer than average.



 
query: 1UWH-Q1
% jobs complete: 100.000
molecules: 39,618,408
hits: 402,003
time: 44:041:13:51:31
Pictures   P T Wan et al Cell (2004) 116.6 p855-67   last updated: 18:14 on 04-MAR-05

Kinesin Kif2C

 

Kinesins play a critical role in tumour and other tissue growth during cell division. Kif2C is believed to depolymerize the microtubule. When Kinesins are inhibited tumours cannot complete the growth cycle and cell death follows. Although the mechanism for apoptosis is not fully understood, Kinesins are now considered to be interesting targets for new anti-cancer drugs.

When running test jobs, the number of hits and the job time varied more widely than many other queries.



 
query: 1V8K-Q2
% jobs complete: 100.000
molecules: 510,665,220
hits: 1,766,162
time: 59:313:11:24:11
Pictures   T Oqawa et al, Cell (2004) 116.4 p591-602   last updated: 06:11 on 13-DEC-04

Mitogen-Activated Protein Kinase 1 partner

 

Mitogen-Activated Protein Kinase (MAPK or MEK) forms part of an important but complex signalling pathway. This uses partner proteins including p14 and MP1 which form a complex which is being targetted in this query.

Job times for this query vary with most jobs taking average times and giving typical numbers of hits.



 
query: 1VET-Q1
% jobs complete: 100.000
molecules: 39,627,720
hits: 80,246
time: 3:000:00:47:36
Pictures   R Kurzbauer et al Proc Nat Acad Sci (2004) 101 p10984-9   last updated: 06:08 on 23-JUL-05

Urokinase plasminogen activator (uPA)

 

Urokinase plasminogen activator (uPA) is a member of the serine protease family of proteins. It is believed that this enzymes plays an important role transporting cancer around the body. If this enzyme is inhibited secondary cancers which can often be fatal are unlikely to develop. This query is based on a different crystal structure to 1sqo-q1.

Jobs for this query are processed slightly faster than typical jobs giving the usual number of hits.



 
query: 1VJ9-Q2
% jobs complete: 100.000
molecules: 510,423,523
hits: 1,662,756
time: 48:186:19:50:21
Pictures   A Schweinitz et al J Biol Chem (2004) 279 p33613   last updated: 12:09 on 04-AUG-05

Histone deacetylase (HDAC)

 

Histone deacetylases (HDACs) are essential to removing of acetyl groups from histone proteins which in turn have a pivotal role in gene expression. It has been suggested that HDAC inhibitors may be useful in the treatment of several types of cancers.

These jobs take slightly longer than 1t69-q1 which is based on a different crystal structure of the same protein.



 
query: 1W22-Q1
% jobs complete: 100.000
molecules: 510,404,711
hits: 3,560,429
time: 103:128:14:35:53
Pictures   A Vannini, To be published (2004)   last updated: 06:10 on 21-JUL-05

Syk Tyrosine Kinase

 

Many Tyrosine Kinases including SYK are inhibited by some anti-cancer drugs. Tyrosine Kinases are also associated with rheumatoid arthritis, inflammation and immunological responses. A lack of selectivity might cause undesirable side-effects and prohibit long term use as preventative treatment.

We expect jobs for this query to give than typical numbers of hits in average times.



 
query: 1XBB-Q1
% jobs complete: 100.000
molecules: 39,651,587
hits: 85,469
time: 4:045:15:49:13
Pictures   S Atwell et al J Biol Chem (2004) 279 p55827-32   last updated: 12:12 on 16-SEP-05

Syk Tyrosine Kinase

 

Many Tyrosine Kinases including SYK are inhibited by some anti-cancer drugs. Tyrosine Kinases are also associated with rheumatoid arthritis, inflammation and immunological responses. A lack of selectivity might cause undesirable side-effects and prohibit long term use as preventative treatment. This query is based on a different crystal structure to 1xbb-q1.

We expect jobs for this query to give than typical numbers of hits in longer than average times.



 
query: 1XBC-Q1
% jobs complete: 100.000
molecules: 39,649,277
hits: 130,314
time: 14:123:07:37:44
Pictures   S Atwell et al J Biol Chem (2004) 279 p55827-32   last updated: 00:05 on 20-SEP-05

Protein Kinase C q

 

Protein Kinase C q (KPC-q) is one of several Protein Kinase C potential targets for anti-cancer drugs. It is understood that KPC-q is associate with leukemic T-cell survival and/or proliferation. An effective and selective inhibitor might have value when administered with chemotherapeutic drugs. KPC-q may also be a useful target for stomach and skin cancers!



 
query: 1XJD-Q1
% jobs complete: 100.000
molecules: 39,627,337
hits: 464,885
time: 9:134:15:18:25
Pictures   Z B Xu et al, J Biol Chem (2004); M Villalba and A Altman CCDT (2002) 2.2 p125   last updated: 12:16 on 02-MAR-05

ErbB1

 

In cancer cells, the ErbB1 receptor tyrosine kinase (also known as EGFR) is sometimes present in higher concentrations than normal. ErbB1 (like ErbB2) is an important signally protein and stimulation leads to growth of the tumour. It may therefore be an important anti-cancer drug target.

We expect this queries to give many hits with job times longer than average.



 
query: 1XKK-Q1
% jobs complete: 100.000
molecules: 39,653,350
hits: 113,377
time: 12:077:05:55:14
Pictures   E R Wood et al Cancer Res (2004) 64.18 p6652-9   last updated: 12:07 on 22-SEP-05

Vascular endothelial growth factor receptor 2 (VEGFR2)

 

VEGF stimulates the growth of blood vessels. The uncontrolled growth of cancer cells is legendary. But this sort of growth requires a lot of blood flow to the cell area. If the blood vessel growth can be restrained, then, in theory, so can growth of the tumour.

In test jobs, this query took longer than typical jobs and gave above average numbers of hits.



 
query: 1Y6A-Q1
% jobs complete: 100.000
molecules: 39,648,347
hits: 320,081
time: 22:308:09:12:11
Pictures   P A Harris et al J Med Chem (2005) 48 1610   last updated: 12:01 on 23-DEC-05

Vascular endothelial growth factor receptor 2 (VEGFR2)

 

VEGF stimulates the growth of blood vessels. The uncontrolled growth of cancer cells is legendary. But this sort of growth requires a lot of blood flow to the cell area. If the blood vessel growth can be restrained, then, in theory, so can growth of the tumour. This query is based on a different crystal structure to 1y6a-q1.

The times for test jobs of this query were typical and gave average numbers of hits.



 
query: 1Y6B-Q1
% jobs complete: 100.000
molecules: 39,649,005
hits: 46,062
time: 5:136:21:37:25
Pictures   P A Harris et al J Med Chem (2005) 48 1610   last updated: 06:03 on 16-DEC-05

Human Double Minute 2 (HDM2) bound to p53

 

The p53 tumour suppressor protein regulates cell proliferation in cancer tumours. The binding of HDM2 to p53 has been observed to inhibit the action of p53 in one-third of soft tissue sarcomas. A small drug molecule which can binding to HDM2 would offer a novel cancer therpy with the potential to enable p53 to stop growth or kill the cancer cells. This query is based on a different crystal structure to 1ycr-q3.

Test jobs for this query gave above average numbers of hits with longer job times.



 
query: 1YCQ-Q1
% jobs complete: 100.000
molecules: 39,648,247
hits: 82,485
time: 19:203:07:28:53
Pictures   P H Kussie et al Science (1996) 274 p921-2.   last updated: 18:02 on 20-DEC-05

Human Double Minute 2 (HDM2) bound to p53

 

The p53 tumour suppressor protein regulates cell proliferation in cancer tumours. The binding of HDM2 to p53 has been observed to inhibit the action of p53 in one-third of soft tissue sarcomas. A small drug molecule which can binding to HDM2 would offer a novel cancer therpy with the potential to enable p53 to stop growth or kill the cancer cells.



 
query: 1YCR-Q3
% jobs complete: 100.000
molecules: 510,683,254
hits: 1,845,791
time: 108:205:05:09:58
Pictures   P H Kussie et al, Science (1996) 274 p948   last updated: 00:13 on 13-DEC-04

Heat Shock Protein 90 (Hsp90)

 

The Hsp90 chaperone is required for the activation of several families of protein kinases and nuclear hormone receptors, many of which are play a prominent role in cancer. When other proteins bind to Hsp90 they are believed to undergo an essential change to how the protein is folded. Inhibiting binding to Hsp90 has been shown to associated with anti-cancer properties.

An effective Hsp90 inhibitor has the potential to be a new class of anti-cancer drugs.



 
query: 1YET-Q1
% jobs complete: 100.000
molecules: 510,660,321
hits: 5,985,276
time: 267:067:07:52:18
Pictures   C E Stebbins et al Cell 89 (1997) p239-250   last updated: 12:17 on 13-DEC-04

Janus kinase 3 (JAK3)

 

Janus kinase 3 (JAK3) occurs in the immune system, where it plays a key role in signal transmission from cytokine receptors. It is a recognised cancer target - DDT (2005) 10.12 p 839-846.

Test jobs for this query took less time than average jobs giving slightly above average numbers of hits.



 
query: 1YVJ-Q1
% jobs complete: 100.000
molecules: 39,645,890
hits: 87,713
time: 5:024:00:14:51
Pictures   T J Boggon et al Blood (2005) 106.3 p996-1002   last updated: 18:09 on 31-OCT-05

C-SRC Kinase

 

The tyrosine kinase domain of C-SRC is a known target for anti-cancer drugs. A recent news story reported the effectiveness of a Bristol-Myers Squibb drug in phase 1 clinical Leukemia trials. (This query uses a different crystal structure without a bound anti-cancer drug).

We expect this queries to give average numbers of hits with typical job times.



 
query: 2SRC-Q1
% jobs complete: 100.000
molecules: 39,621,892
hits: 173,432
time: 6:230:06:11:23
Pictures   W Xu et al Mol Cell (1999) 3.5 p629-38   last updated: 12:09 on 10-APR-05

Mitogen Activated Protein (MAP) Kinase

 

Mitogen Activated Protein (MAP) Kinases are signaling proteins that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. The MAP kinase this query is based on is known as ERK2 (extracellular-signal-regulated kinase 2) and plays a role in cellular differentiation or proliferation.

For this query the times taken by test jobs were longer than usual giving more hits.



 
query: 3ERK-Q1
% jobs complete: 100.000
molecules: 510,443,940
hits: 3,259,956
time: 310:016:01:09:53
Pictures   Z Wang et al Structure (1998) 6.9 p1117-28   last updated: 00:00 on 26-JAN-06

Mitogen Activated Protein (MAP) Kinase

 

Mitogen Activated Protein (MAP) Kinases are signaling proteins that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. The MAP kinase this query is based on is known as ERK2 (extracellular-signal-regulated kinase 2) and plays a role in cellular differentiation or proliferation. This query is based on a different crystal structure to 3erk-q1.

For this query the times taken by test jobs were below average giving typical numbers of hits.



 
query: 4ERK-Q1
% jobs complete: 100.000
molecules: 39,650,326
hits: 106,371
time: 4:170:16:58:27
Pictures   Z Wang et al Structure (1998) 6.9 p1117-28   last updated: 00:05 on 30-OCT-05

RAS Proteins

 

RAS proteins give a chemical "message" that activate cell growth. Without this signaling factor, the cell doesn't "know" to grow. Inhibiting RAS in cancer cells means an end to their uncontrolled growth. This query was originally started with a subset of 3147 jobs and is now being extended to 7999 jobs.



 
query: 821P-Q1
% jobs complete: 100.000
molecules: 78,761,120
hits: 183,753
time: 2:308:17:02:34
Pictures   A J Scheidig et al (1992) Philos. Trans. R. Soc. London Vol 340 p263   last updated: 18:15 on 06-SEP-03

RAS Proteins

 

RAS proteins give a chemical "message" that activate cell growth. Without this signaling factor, the cell doesn't "know" to grow. Inhibiting RAS in cancer cells means an end to their uncontrolled growth. This query is a revision of 821P-Q2 with more scope for interactions. Most test jobs gave many more hits and took much longer.



 
query: 821P-Q3
% jobs complete: 100.000
molecules: 508,978,450
hits: 3,860,763
time: 202:135:17:44:51
Pictures   A J Scheidig et al (1992) Philos. Trans. R. Soc. London Vol 340 p263   last updated: 08:14 on 29-SEP-03

RAS Proteins

 

RAS proteins give a chemical "message" that activate cell growth. Without this signaling factor, the cell doesn't "know" to grow. Inhibiting RAS in cancer cells means an end to their uncontrolled growth. This query is a revision of 821P-Q1 with an improved scoring function and is the first to be executed for 51352 jobs (approximately 0.5 billion molecules). We have suspended downloading new jobs for this query as we are unhappy with the hit profile.



 
query: 821P-Q2
% jobs complete: 0.000
molecules: 0
hits: 0
time: 0:000:00:00:00
Pictures   A J Scheidig et al (1992) Philos. Trans. R. Soc. London Vol 340 p263   last updated: 12:00 on 26-JAN-06