OSA Series 2 Meeting 17th July 2020

[mattodd]

(Didn't record it, sorry, but we should be doing that. In the Zoom were me, @danaklug and @edwintse.

First meeting after UCL lab lockdown! Headline: chemistry re-starting.

1) Community updates: We need meetings like this on Youtube. We need more science update tweets. Let's make a video, using the Tha/Dana protocol (OpenSourceMalaria/TechOps#3).

2) Are relevant lab books clearly linked? Yes, mostly here.

3) We're waiting for confirmation that the relevant samples that are in a fridge at UNC and are still available. Mat to ping the team (incl @AlvaroLor).

4) Mechanism of action: Lee Graves at UNC contacted re relevant experiments (#15). He's asked about the "base cell type" for the experiment. Don't understand this Q, so will seek clarity from the team.

5) Monash measurement of in vitro PK. #13 Green light to ship. 3-4 mg each, accurately weighed. The team have sent the necessary customs forms. Mat to forward to UNC and thank the Monash team.

6) Who is doing the MRSA and tox screening for all analogues? Mat to chase Paul Stapleton and Andreas Schatzlein within UCL SoP who have expressed interest and willingness. Other potential bio testing labs welcome, obviously.

7) Synthetic Chemistry. @danaklug has shared the nice immediate chemistry plan (#16), which involves resynthesis of active and inactive controls, then variation in the thiophene part of the structure. @edwintse and @danaklug to divvy up synthetic tasks and to seek now new commercially available starting materials that will allow simple variation of imidazole part of structure.

8) Compound numbering. Adopt code system from opensourceantibiotics/murligase#9 and here that captures batch and salt codes (Done for Series 2 molecules to date). Update the supersheet with corrected numbers and codes. Will probably need to address this also for OSA Series 1 at some point, lower priority.

9) Some interest from Pfizer (TBC) in assessing the molecules for metabolic transformation (and isolating the metabolites). Mat to confirm.

10) We only have money currently for about 9 in vitro PK evaluations from Monash, plus on final in vivo. It'd be very useful to have a rough, high throughput experimental assessment of metabolic liability. What can we use? #7 ? Academic or industrial interest? @danaklug to share search she's done.

11) Design criteria for molecules must keep an eye on logP (use Datawarrior) and predicted clearance (use SMARTCyp, right @drc007 ?).

Any and all comments please go ahead. We'll try to cross off all the above when done before closing this issue.

[danaklug]

@mattodd re: point 8 - I've updated the Series 2 molecules with salt and batch codes (new columns in the spreadsheet). Re: point 10 - New issue (#18) has been started.

[mattodd]

Closing since we've moved on to #19