Projects - Cancer

Protein

Description

Statistics

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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!

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.