OSA Meeting Friday Sept 4 2020

[danaklug]

Meeting 4/9/20 at 2pm UK time at https://ucl.zoom.us/j/92800004715. This page follows on from #23.

Recording is here. On the call: @danaklug @edwintse @drc007

1. Mechanism of action: Lee Graves at UNC was contacted re relevant experiments (Mechanism of action #15). Will now do. Action: Dana to chase this in 2 weeks.

2. Monash measurement of in vitro PK. Complete. Awaiting data. No action needed.

3. MRSA and tox screening. Paul Stapleton (UCL School of Pharmacy) ready to screen by next Wed. We will have ca. 10 compounds. Action on Mat to check how much needed.
   Tox: delay in Schatzlein lab (due to lockdown), not as crucial. Action on Mat to monitor. No obvious alternatives.

4. Pfizer Biofunctionalisation: We have active and inactives to ship to them. We can do that now. Action on Mat to ask how much they need, etc. Note from @drc007: Need to verify activity of all compounds in MRSA assay.

5. Hypha: Mat has met and corresponded with the company. Action Mat to report back on what's possible via collaboration.

6. Series Origin/Similarity Landscape: Mat in touch with James Callahan (GSK), the corresponding author on the original article reporting these compounds. Mat awaiting clearance from GSK for sharing publicly, and (Action) will report back.

7. Design criteria for molecules must keep an eye on logP (use Datawarrior) and predicted clearance (use SMARTCyp). Update: also FAME <-- @drc007 contacted the team, details on wiki. Action on Dana to install these tools on wiki so that we can delete from agenda.

8. Community updates: Need video update using the Tha/Dana protocol (How Can We Democratize Making 30-second Captioned Videos for Updates? OpenSourceMalaria/TechOps#3). When we get first MRSA results.

9. Gram+/Gram- results. Dig out activity report from CO-ADD? @AlvaroLor doesn't have it, so (Action) Mat to write to @TwistedSwisster to track it down, alternatively direct write to COADD. Question remains: are these compounds active against other gram +ves?

10. Synthetic Chemistry Update was given in meeting by @edwintse and @danaklug - slides below and posted in code area.
    Key: inactive dimethoxy compound made DMK132-1, Dana proposed triazoles, which can be screened as mixtures. Ed has made control phenyl compound, which would be good substrate for alfone/sulfoxide analogs.

AOB:
(after meeting): Dana previously mentioned impurity in NMR spectra (#23 (comment)). Was this resolved?

Actions other than the chemical targets discussed (can be checked as complete after the meeting).

• ACTION ITEM: Mat to monitor possibility of SoP-based tox screening.
• ACTION ITEM: Dana to chase MoA experiments on Sept 18th.
• ACTION ITEM: Mat to check how much compound needed for MRSA screening.
• ACTION ITEM: Mat to check how much needed for Pfizer biofunctionalisation experiments.
• ACTION ITEM: Mat to report back on collaboration possibilities with Hypha.
• ACTION ITEM: Mat to report back from GSK on what can be shared publicly about the series history.
• ACTION ITEM: Dana to install software tool links on wiki.
• ACTION ITEM: Mat to contact Bill Zuercher about original CO-ADD screening report.
• ACTION ITEM: Mat This meeting video to be posted on YouTube.

[MFernflower]

Not certain if I can attend tomorrow but i'll try

[danaklug]

Links to SMARTCyp, FAME, DataWarrior, and SwissADME have been added to "Submissions, Resources and Data" wiki page

[edwintse]

Synthetic chemistry slides (n.b. it now appears that the direct oxidation to the sufone EGT 479-2 has instead led to the pyridine N-oxide compound):