Projects - Respiratory Disease

Protein

Description

Statistics

The name Tumor necrosis factor-a (TNF-a) originates from its ability to kill tumor cells. It is a cytokine that induces protective inflammatory reactions but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Our interest is in respiratory disease where it is also a recognised potential drug target.

In test jobs, this query gave more hits than usual in typical times.

It has been suggested that Expoxide Hydrolase might alleviate inflammation in the lungs.

We expect this query to give typical numbers of hits with shorter than average job times.

Phosphodiesterase 4 (PDE4) is a recognised anti-inflammatory drug target. However, it has been suggested that existing inhibitors lack the specificity or have problematic side-effects.

The time taken for jobs for this query is typical giving few hits.

Blocking Interleukin-1 receptor type 1 has the potential to reduce the effect of elevated Interleukin-1 levels which is associated with inflammation in the lungs and other tissues.

We expect this query to give average numbers of hits with longer than typical job times.

This kinase converts thymidine monophosphate (TMP) to the di- and tri-phosphates. Inhibiting this process would be expected to significantly disrupt the cell cycle (ie growth). There is sufficient variation from the mammalian form and that found in mycobacterium tuberculosis to give scope for selective inhibition.

This query gave relatively few hits from a selection of test jobs.

UDP-Galactopyranose mutase is an essential enzyme for mycobacteria including tuberculosis. It makes Uridine diphosphogalactofuranose (UDP-Galf) which is converted to the d-galactofuranose (Galf) found in cell walls. Fortunately the enzyme is not found in humans reducing the scope for site-effects.

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

MRP14 is a Ca(2+)-binding protein from the S100 family of proteins thought to play a role during inflammation of membranes.

We expect this query to give above average numbers of hits with longer job times than typical.

Macrophage Elastase Mmp-12 is a member of the family of matrix metalloproteinases (MMPs) that play an important role in inflammatory processes contributing to tissues changes and destruction. In the lung, elastin is destroyed and it has been suggested that Mmp-12 activity causes emphysema.

The jobs for this query are typical (ie around 12 hours on a 1GHz PC).

The hormone histamine plays a key role in bronchial asthma as well as gastric acid secretion. Histamine interacts with histamine methyltransferase. Molecules which block this interact have capability to be new anti-histamine drugs for asthma treatment.

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

The hormone histamine plays a key role in bronchial asthma as well as gastric acid secretion. Histamine interacts with histamine methyltransferase. Molecules which block this interact have capability to be new anti-histamine drugs for asthma treatment. This query is based on a different crystal structure than 1jqd-q2.

We expect this queries to give normal numbers of hits with in typical times.

Interleukin-10 receptor is a recognised anti-inflammatory target. It is also considered a possible drug target for Crohn's disease and other diseases with serious inflammation - see Drug Discovery Today (2005) 10.2 p93-106.

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

The coronavirus family exhibit one main proteinase sometimes described as '3C-like' because the nature of the catalytic site which fulfils a crucial role in the regulation of the virus life-cycle. The 3-dimensional structure of the SARS main proteinase has not yet been determined experimentally but there is evidence to suggest that it is similar to other coronaviruses. For this project we have selected the structure of a coronavirus which can cause gastroenteritis. The catalytic or active site of this enzyme includes Cysteine and Histidine residues which are considered to be essential for the normal function of the protein. We are seeking small molecule inhibitors which interact with at least one of these residues.

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response. This query targets a different binding site to 1mf7-q2.

Test jobs for this query gave more hits and took longer than typical jobs.

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response.

We expect this query to give variable numbers of hits with variable job times.

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammation response. This query targets uses slightly different search criteria to 1mf7-q1.

Test jobs for this query gave more hits and took longer than typical jobs.

7,8-Dihydroneopterin Aldolase (DHNA) has no human equivalent but is an essential enzyme in bacteria including Mycobacterium Tuberculosis, playing a critical role in folate synthesis. This is a novel antibacterial target which is interesting because bacteria in contrast to humans (and other mammals) cannot absorb folate from their environment. Without folate bacteria cannot grow!

This query gives above average number of hits and longer than typical job times.

The search for novel PDE4 inhibitors is currently one of the most active fields in the pharmaceutical industry. PDE inhibitors are believed have good potential in the treatment of chronic inflammatory diseases such as asthma as well as rheumatoid arthritis. There are at least four major subtypes of PDE receptor and selectivity may be important in order to reduce side-effects.

This protein plays an important role in Mycobacterium Tuberculosis and it has been suggested that a molecule which inhibits it may have some drug potential. This is especially the case in drug-resistant forms when inhibit is expected to increase the effectiveness of antimicrobial agents.

We expect this queries to give average numbers of hits. It requires THINK 1.25a or later versions.

The coronavirus family exhibit one main proteinase sometimes described as '3C-like' because the nature of the catalytic site which fulfils a crucial role in the regulation of the virus life-cycle. The 3-D structure of the SARS virus proteinase has been determined by Professor Hilgenfeld at the University of Luebeck who has kindly made this structure available to Find-a-Drug. The catalytic or active site of this enzyme includes Cysteine and Histidine residues which are considered to be essential for the normal function of the protein. As part of the collaboration with Professor Hilgenfeld, the hits from this work will be made available to his group and they will attempt to confirm the binding to the protein site.

Cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in cystic fibrosis. Its Nucleotide-binding domain 1 (NBD1) is often observed with at least one mutation although the biochemical significance of this is not fully understood. This is a speculative query to find molecules which might be therpeutically useful.

We expect this query to give above average numbers of hits with variable job times.

Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. An inhibitor is sought as a potential treatment for Asthma.

We expect these jobs to give more than typical numbers of hits with with some longer than typical job times.

7,8-Dihydroneopterin Aldolase (DHNA) has no human equivalent but is an essential enzyme in bacteria including Mycobacterium Tuberculosis, playing a critical role in folate synthesis. This is a novel antibacterial target which is interesting because bacteria in contrast to humans (and other mammals) cannot absorb folate from their environment. Without folate bacteria cannot grow! This query is based on a different crystal structure to 1nbu-q1.

This query gives above average number of hits and longer than typical job times.

Interleukin-1 beta convertase (ICE) is also known as Caspase-1 and plays an essential role in the production of Interleukin-1 beta. Suppressing the level of Interleukin-1 beta can reduce inflammation which is especially troublesome in the lungs. It has also been suggested ICE inhibitors may be a useful therapy for Crohn's disease.

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

NF-k-b is a transcription factor. It has been suggested that it is a viable anti-inflammatory protein target which may be useful in treating respiratory diseases.

We expect this query to give fewer hits than normal in less time than typical jobs.

This enzyme is responsible for a step in the synthesis of trehalose-2-sulfase (T2L) which is a key component of sulfolipid-1 (SL1) In mycobacterium tuberculosis (the bacterium which causes TB), inhibiting this enzyme stops T2L being made with the consequence that SL1 is no longer formed. A sulfotransferase inhibitor might be a novel therapy for TB.

This query gave above average number of hits and slightly longer than typical job times.

This kinase converts thymidine monophosphate (TMP) to the di- and tri-phosphates. Inhibiting this process would be expected to significantly disrupt the cell cycle (ie growth). There is sufficient variation from the mammalian form and that found in mycobacterium tuberculosis to give scope for selective inhibition. This query is based a different crystal structure to 1g3u-q1.

In test jobs, this query took less time than typical jobs and gave below average numbers of hits.