HIV - 1A8G-Q1 - HIV Protease

HIV
1A8G-Q1
HIV Protease

HIV protease is a recognised drug target. However, mutations of this protein render many of the inhibitors ineffective against mutant strains.

We expect this query to give above normal numbers of hits and average job times on a typical PC.

A B Smith III, J Med Chem (2003) 46.10 p1831-44

Cancer - 1KSW-Q1 - C-SRC Tyrosine Kinase

Cancer
1KSW-Q1
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.

Methodology - 821P-Q4 - Hit Comparison (better than 821P-Q3 ?)

This is part of a sequence which uses less stringent queries that give more hits. Our interest is whether any of these hits are better than the 821p-q3 hits.

For anyone who wants a more technical answer 821p-q4 is a 3 centre pharmacophore search with a lower (better) cutoff than the corresponding 4 centre pharmacophore query.


Methodology
821P-Q4
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 part of a series which explores the use of less stringent queries that give more hits. We hope to gain an insight into whether better hits are generally included.

Test jobs gave many more hits and took longer than average jobs.

A J Scheidig et al (1992) Philos. Trans. R. Soc. London Vol 340 p263

Osteoporous - 1AU4-Q1 - Cathepsin K

Proteome
1AU4-Q1
Cathepsin K

Cathepsin K has been identified as playing a key role in bone matrix resorption and inhibiting this process is likely to have benefit to at least some individuals who suffer from Osteoporous. This query is based on a different crystal structure to 1atk-q1.

The time taken for test jobs for this query varied some giving above average numbers of hits.

F X Tavares et al J Med Chem (2004) 47.3 p588-99

Planned Stats Server Outage (on Monday 25th OCT)

There is a planned outage of the stats pages.
This Monday - 24th October 2005
12:00hrs and 18:00hrs GMT

Quote THINK

Due lack of electrical power, there will be no stats updates at 12:00 or 18:00 on Monday 24 October. We apologize for any inconvenience. No results will be lost as a result - just their processing delayed.

Forum Down (.org.uk site wide) - FIXED and Running again

Well the forums are down along with the rest of www.find-a-drug.org.uk site.

No reasoning why yet (last time it was DDOS typical activity)

Scribe (moderator) has not been able to contact THINK yet.

please visit forums for the time being :D



Note: That means www.findadrug.org.uk (job get) and www.find-a-drug.org.uk (job send) are also down. No need to worry as they will just roll over if needed to the other two servers.


It is fixed and running again
Reason

This appears to have been caused by a bug in the cPANEL server configuration software.

(If anyone is really interested there was a mailing list and a mailing address with the same name which we believe was responsible for a circular email).

Alzheimer - 1PB8-Q1 - N-Methyl-D-Aspartate (NMDA) Receptor

Proteome
1PB8-Q1
N-Methyl-D-Aspartate (NMDA) Receptor

N-Methyl-D-Aspartate (NMDA) antagonists are recognised as potentially useful as a therapy for Alzheimer's Disease - see DDT (2005) 10.11 p 750. Over stimulation of this receptor appears to be related to neurodegeneration and blocking it has some therpeutic benefits. This approach is rather different from many of the other Alzheimer's Disease drugs which are being developed. This queries is based on a different crystal structure to 1pbq-q1 and 1pb7-q1.

The test jobs times took longer than average and gave very few hits.

H Furukawa and E Gouaux EMBO J (2003) 22.12 p2873-85

Nickname and Email configuration changes

Due to people forgetting their email address that they used when installing the Find-a-Drug client and that installation no longer being available or they need to change old installations that are long gone to a new email address. Find-a-Drug are developing an automated system (I assume due to the increasing time this is obviously taking them to sort out for people) to find out your email address and change it.

Quote THINK

We are planning to make a web interface available sometime next month to allow Nicknames and Email addresses to be changed for installations which have been deleted (ie inactive - having not returned any jobs for a period of time).

The way this will work is that members will use a web form to request the list of member numbers for a Nickname. Using this form a member can request an email to be sent to the registered email address for a member number. This email will include a link to another form which uses a password included in the email to change the Nickname, Email address and/or team identify.

We recognise that this will not help members who did not enter a valid email address or no longer have access to the registered email address!

Please note the last part,
this will not help members who did not enter a valid email address or no longer have access to the registered email address

HIV - 1RQL-Q1 - Deoxyhypusine Synthase

HIV
1RQL-Q1
Deoxyhypusine Synthase

Inhibiting this enzyme suppresses hypusine formation and the activation of a cofactor in the HIV-1 Rev regulatory protein. This inhibits the replication of the virus. It has been suggested that this is an attractive drug target because few side-effects are anticipated and especially useful for strains of HIV resistant to other drugs. This query is based a different protein crystal structure to 1dhs-q1.

The time taken by our test jobs was variable with some jobs taking longer than typical jobs but mostly giving fewer hits.

D I Liao et al, Structure (1998) 6 p23

Cancer Query 3ERK-Q1 has been Extended

Cancer Query 3ERK-Q1 Mitogen Activated Protein (MAP) Kinase has been extended into a larger set of molecules.

Alzheimer - 1PB7-Q1 - N-Methyl-D-Aspartate (NMDA) Receptor

Proteome
1PB7-Q1
N-Methyl-D-Aspartate ( NMDA ) Receptor

N-Methyl-D-Aspartate (NMDA) antagonists are recognised as potentially useful as a therapy for Alzheimer's Disease - see DDT (2005) 10.11 p 750. Over stimulation of this receptor appears to be related to neurodegeneration and blocking it has some therpeutic benefits. This approach is rather different from many of the other Alzheimer's Disease drugs which are being developed. This queries is based on a different crystal structure to 1pbq-q1.

The test jobs times usually took longer than average and very few hits.

Ischemic Stroke - 1FTM-Q1 - Glutamate Receptor 2 (GluR2)

Proteome
1FTM-Q1
Glutamate Receptor 2 ( GluR2 )

Ischemic stroke is the third leading cause of death in developed countries. GluR5 plays an important role in neurotransmission in the brain forming part of the AMPA receptor channels. GluR5 has been suggested as a target for stroke therapy because it mediates signals that damage vulnerable neurons.

The time taken by test jobs was variable with some giving above average numbers of hits.


M M Soundarapandian et al Mol Neurobiol (2005) 32.2 p145-56

Cancer - 1BIW-Q1 - Stromelysin

Cancer
1BIW-Q1
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.


R C Rizzo et al J Med Chem (2004) 47.12 p3065-74

Osteoporous - Cathepsin K - 1ATK-Q1

Proteome
1ATK-Q1
Cathepsin K

Cathepsin K has been identified as playing a key role in bone matrix resorption and inhibiting this process is likely to have benefit to at least some individuals who suffer from Osteoporous.

These jobs take less time than typical jobs giving average numbers of hits.

F X Tavares et al J Med Chem (2004) 47.3 p588-99

Multiple Sclerosis Project Progress

After a question was raised by nozi

THINK gave a snippet of information on Multiple Sclerosis progress with the collaborators,

I have been advised that some samples have been purchased for testing in the laboratory in the coming weeks. However, it is unlikely we will be told which molecules show activity - although I am hoping a general overview will be disclosed.

Antibacterial - 1KIJ-Q1 - Gyrase B

Proteome
1KIJ-Q1
Gyrase B

Gyrase is a recognised antibacterial target. However, existing inhibitors have not had therpeutic potential because of serious side-effects and mutant resistance. It may be possible to find alternative inhibitors which do not have these limitations. This query is based on an alternative crystal structutre to 1aj6-q1.

Job times for this query varied often giving above average numbers of hits.

A Tanitame et al J Med Chem (2004) 47.14 p3693-6

HIV - 1YZL-Q1 - Rab9 GTPase

HIV
1YZL-Q1
Rab9 GTPase

It has been suggested that Rab9 GTPase is a key cellular component for a variety of virus related diseases by facilitating vesicular transport. Our main interest in their target is as a HIV-1 drug target. This query is based on a different crystal structure of the same protein as the 1WMS-Q1 and 1S8F-Q1 queries.

We expect this query to give above average numbers of hits with job times less than 12 hours on a typical PC.

J G Wittmann and M G Rudolph, FEBS Lett (2004) 568 p23

Cancer - 1L2I-Q1 - Estrogen-α Receptor

Cancer
1L2I-Q1
Estrogen-α 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.

S Kim et al, J Med Chem (2004) 47.9 p2171-5

SIGnature v2 released (aka Berni sig stat image generator)

Berni has update the SIGnature to v2, this is probably more commonly known as the Signature Stat Image Generator



Changes Include

- Upload and user your own backgrounds
- Image size = size of the background
- Team and User stars on the same image
- Fully customizeable position of the stats
- Integrated Short URL enabler (similar to TinyURL)
- "generator value restore" function included
- Made it easy for Teams to use the same designs

Now you can have something like



See updates and report bug in the forum thread here

HIV - 1B6L-Q1 - HIV Protease

HIV
1B6L-Q1
HIV Protease

HIV protease is a recognised drug target. However, mutations of this protein render many of the inhibitors ineffective against mutant strains.

We expect this query to give above normal numbers of hits and average job times on a typical PC.

A B Smith III, J Med Chem (2003) 46.10 p1831-44

Hepatitis C - 1DXP-Q1 - Hepatitis C Virus NS3 Serine Protease

Proteome
1DXP-Q1
Hepatitis C Virus NS3 Serine Protease

NS3 serine protease expressed by the hepatitis C virus is a recognised target for drug design. While some high molecular mass peptides have worked in the laboratory they are not suitable as drugs and the search for typical drug-like molecule has been less successful. This query is based on a different crystal structure to 1DY9-Q2 and 1DY8-Q1.

The time taken by test jobs was often above average giving more hits than usual.

S Di Marco et al J Biol Chem (2000) Vol 275, p7152

Pain Relief - 1TXF-Q1 - Kainate receptor (GluR5)

Proteome
1TXF-Q1
Kainate receptor ( GluR5 )

Glutamate is the primary neurotransmitter in the mammalian nervous system. GluR5 kainate receptor has been shown to be associated with pain transmission. An inhibitor would have potential for pain relief with fewer side-effects. This query is based on a different crystal structure to 1ycj-q1.

Test job times and number of hits for this query varied.

P Naur et al FEBS Lett (2005) 579.5 p1154-60