OSA Meeting Friday Nov 5th 2021

[edwintse]

This page is draft until this text is removed.

Meeting Nov 5th 2021 at 2pm UK time at https://ucl.zoom.us/j/92800004715. Follows on from #95

Recording:

On the call:

1. Discussion of latest MRSA results (#99)
   • Control compound, vancomycin, and SAR filler 1018 performing as expected. All other activity hovering around 8 ug/mL.
   • @QSimpson et al. working on alkylating -NH compounds from this set (OSA_1022 etc) and will send to UCL when complete.
   • Further compound synthesis not justified based on current data
2. Publication
   • Tox (Alex) and MoA (Lee Graves) results outstanding
   • Possibility to measure clearance/solubility for 4-5 compounds and in vivo data for 1 compound at Monash
3. Discussion of which compounds to ship to NEU for ADME data
   • There are 12 slots available (LogD, PPB, HLM Clint, rat hepatocyte Clint, aq. sol.)
   • Focus on diversity by clustering Series 2 compounds and choosing representatives (@edwintse)
4. Alex's tox data
   • Alex still working through completing the data table, shared results for OSA_821, 983
   • Compounds are more toxic using the recovery protocol, which could potentially indicate a toxicity mechanism involving cell cycle or DNA repair.
   • Alex to look into the feasibility of a non-cellular DNA binding assay.

ACTIONS

• [x] @edwintse to cluster Series 2 compounds and look for candidates for ADME evaluation
• [ ] Alex to discuss DNA binding assays with Gary

PREVIOUS ACTIONS

• [ ] ALL: consider SAR holes identified in #94
• [ ] @MFernflower to capture commercial searching in part of molecule procurement workflow in wiki here
• [ ] @QSimpson to see whether an open CDD sheet/vault is Googleable
• [ ] @drc007 to look into solutions for converting master list to something Googleable. Chris has implemented this - he's running something locally that extracts the data, then uses RDkit to create images of structures, then sends that to this html page that is on the mur ligase repository. Useful because we can link to it and it should be Googleable. It's not possible to have a Readme up top, so it's important that the sheet contains links for the molecules so that interested viewers know where to go for more. i.e. the OSA Master List needs to include links to where to go for more. @drc007 to check that the current page is being searched by Google. If works then we need an action item to consider how best to add "more info" links.