OSA Meeting Friday July 2nd 2021

[mattodd]

Meeting July 2nd 2021 at 2pm UK time at https://ucl.zoom.us/j/92800004715. This page follows on from #79.

Recording is here.

On the call: @mattodd @MFernflower @danaklug @Giada-chem @edwintse and Alex Vaideanu (UCL)

1. Screening

a) Potency

• @danaklug has updated SAR tables in wiki.
• Benzimidazoles going to DNDi? @edwintse <-- we didn't talk about this meeting!
• Compounds at NEU described by Quillon in New compounds from NU #78 will be shipped to UCL? (Excluding 136 and 139?)

b) Parallel DNDI assay
Compounds have arrived in DNDI lab. Results have been posted in #60. @danaklug to colour-code. Interesting activity, but again tox is tracking with potency. The Northeastern team are interested in some of these compounds, and we could jointly pursue and share.

c) Human Cytotox
Alex V updated in meeting. Tox similar to last time. Alex is generating a complete set of data for the paper. We need the Excel sheet and the pic for the wiki.
Check on DNA binding: Alex will ask around in UCL to see if we can do a simple DNA interaction assay to establish if there is DNA binding.
Check on apoptosis: let's wait for data back from Lee Graves before we address this since it's quite a lot of work for Alex.

2. Synthetic Chemistry
   Current targets were described in OSA Meeting Friday June 25th 2021 #79. They remain the same.

• NEU N-linked, N-methylated compounds.
• @flavioemery "homology series".
• @Giada-chem aromatic amines in the northwest position (Giada thinks she's gotten the first compound!)
• @danaklug doing one-pots
• Commercial amides found by @MFernflower.

3. in vitro PK
   @edwintse has updated wiki with metabolite data.
   The removal of the 5-membered ring in the east of the molecule where the metabolism is happening. @danaklug was making attempts at doing that chemistry in (where are the structures shown?).
   New ADME data obtained and drawn in ADME Data (June 2021) #80. Discussion: @danaklug will add in the logD data we also have. There are some excellent numbers here, but for inactive compounds. Some of the solubilities are very high. How come? Some of the clearances of those highly soluble compounds are also excellent. It would be useful to have data not on the 5-5 ring but instead on the 5-6 ring (that lacks the known metabolic liability). @danaklug to approach @loriferrins about this possibility.

4. Community updates
   a) Newsletters. Third newsletter needs to be written by @mattodd. Focus on S2.

b) Can we start to make use of the Planetary Forge Twitter Bot? Described at mattodd/blog#2. Would need an extra column inserted into the Master List.

5. Mechanism of Action
   @mattodd has reached out to Lee Graves to ask if MoA experiments can resume. Lee is engaging with Mat by email about this and will attend a future meeting.

6. ELN
   @danaklug or @edwintse to try again (Action) Labarchives' molecule sketching facility to see if the ELN page is Google-able. i.e. sketch a molecule from OSA using the drawing facility, and check each day to see if it is indexed. ELN pages on which strings have been manually pasted are indexed (@mattodd checked this). Can we do away with manual strings pasting? Separately, @mattodd found that the OSA molecule spreadsheet is not indexed. @drc007 said he would check this out (Action). <-- @drc007 can we remove this, or are further actions needed?

Previous guest appearance by Isabelle Giraud who described, with @drc007, how to auto-import the OSA Master List into Datawarrior. Action: install on wiki a simple how-to for how to visualize OSA molecules, and filter to this series.

AOB:

• Action on @edwintse to include searching using Manifold in wiki somewhere logical (tech-ops page).

Actions

• @danaklug to look into whether manual strings are still needed in Labarchives, or whether molecule sketching facility is sufficient.
• @edwintse to install reference to e.g. Manifold (and other resources) on wiki.
• @drc007 to look into why the OSA molecule sheet is not Google-indexed.
• @mattodd to write and send next OSA-S2 newsletter
• NEU student team get Github accounts
• NEU team to ship compounds mentioned above in AOB
• Jyoti to upload NEU synthesis slides.
• @flavioemery to upload the pic of synthetic route to this GHI
• NEU search to see whether @loriferrins NEU team have analogs of OSA1000 already, to explore that core a little more.
• @danaklug to colour-code DNDi data in DNDi Testing (Tox + Leish/Chagas/Sleeping Sickness) - RESULTS ARE IN! #60.
• @danaklug to add in logD data in ADME Data (June 2021) #80.
• @danaklug to see whether ADME data might be obtained on the 5-6 system.
• Alex V to complete write-up of tox data.
• Alex V to ask about possibility of DNA interaction experiment.
• This meeting to be posted on YouTube.