malaria research community

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06 Jun

ChEMBL-NTD actives

Published by pylioja

I thought I would just quickly summarise some of the hits that come up in ChEMBL-NTD for the core structures of the compounds we're working with at the moment. The most active compounds, the "near neighbours", contain both a 2-iminothiazolidinone and 2,5-dialkylpyrrole moiety.

01 Jun

Single crystal X-ray

Published by pylioja

Subject 

Technical Note

We've just had a single crystal x-ray structure back for OSM-S-9 (PMY 35-1) confirming which isomer of the product we've been making.

The structure shows the acyl group on the N-phenyl nitrogen rather than on the iminothiazolidinone nitrogen. It's nice to have this cleared up.

Open Source Drug Discovery for Malaria Meeting - Session 2, Part 1, Richard Jefferson

Published by MatTodd on 23 May 2012 - 12:41am

Subject 

Results

Part of the second session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Richard Jefferson, Cambia and the Institute of Open Innovation.

 

14 May

Shop Till You Hit

Published by cdsouthan

Subject 

Request for Help

I have been helping out with public searches for the OSM-S compounds.  One of the many utilities of PubChem is as a meta-vendor portal.  The question immediately arises as to what analogs of the more potent hits might be available for purchase and testing via the outlinks provided in PubChem.  I consider myself  able and willing to navigate the bioactivity spaghetti links but this is the first time I have done any serious ferreting through the vendor maze.  Because this turned out to be unexpectedly difficult I have written a personal blog post  that I hope will be informative for the proje

Late Stage Gametocyte Assay for Arylpyrroles

Published by MatTodd on 7 May 2012 - 2:13pm

Subject 

Results

Four of the arylpyrroles/near neighbors have been tested in a late stage anti-gametocyte imaging assay, with interesting results.

hERG Assay for Two Potent OSM-S Compounds

Published by MatTodd on 7 May 2012 - 1:26pm

Subject 

Results

One of the most potent compounds identified to date in the OSDD malaria project, the near-neighbour analog OSM-S-35 (ZYH3) was subjected to the hERG assay along with one of the original TCAMS GSK compounds which in this project has the tag OSM-S-5.

Raw data are here, plus spreadsheet here.

Metabolic Studies on a Set of Arylpyrroles

Published by MatTodd on 7 May 2012 - 12:54pm

Subject 

Results

Eight compounds - two GSK originals and 6 promising-looking compounds made during this project were examined by Sue Charman's lab at Monash for metabolic degradation in vivo. In human terms that means they were tested (on a simplistic level) to see whether the compounds would last long in the blood or whether they would likely be metabolised. As part of these studies the solubilities of the compounds were evaluated.

Bioisosteric transformation maps

Published by wallacei on 14 April 2012 - 3:27pm

Subject 

Request for Help

It is common in drug discovery to have a highly potent hit that has to be optimised to remove undesirable characteristics such as poor oral bioavailablity, metabolic stability or toxicity. In our case, we have a number of highly potent compounds that have quite a high LogP, which is considered a warning sign for both a promiscousity (i.e. binding to many compound targets in vitro) as well as poor oral bioavailabilty (as it breaks the Lipinski Rule of 5).
 

Purchasable compound similarity maps

Published by wallacei on 11 April 2012 - 4:38pm

Subject 

Request for Help

There are over 5 million compounds that are available to purchase according to the meta service, E-molecules (http://www.emolecules.com).
It is worth exploring these in the context of the OSDD project as it will identify compound series' that are very easy to explore by purchasing analogues (i.e SAR by catalogue) aswell as identifying compounds that are potentially more sythetically accessible than others (i.e. if there many close neighbours these compounds might be easier to make than others). 

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