AJLloyd105
commented
2 months ago Hi All Today's presentation from Warwick, MurC hits from Atomwise characterised wrt dose dependence IC50 determination, first eight of 24. 090424 III.pptx
Closed Yuhang-CADD closed 2 months ago
AJLloyd105
commented
2 months ago Hi All Today's presentation from Warwick, MurC hits from Atomwise characterised wrt dose dependence IC50 determination, first eight of 24. 090424 III.pptx
Yuhang-CADD
commented
2 months ago Adrian's summary of inhibition of P. aeruginosa MurC with the Atomwise compound set sent 23.05.23 and 25.07.25. It comprises the IC50 determinations for the 24 atomwise molecules that generated greater than 50% inhibition of P. aeruginosa MurC.
This is the IC50 data corresponding to the single concentration work previously done. I now have IC50 data for the atomwise hits on MurD and MurE from previous work, which has been posted, with MurF left to do. Once MurF is completed, I can give a fuller picture of the multi-targeting capabilities of the Atomwise molecules we have been working with.
Unfortunately, the potency of any of the MurC hits only extend to 14 uM, however there is sufficient spread of IC50 values across the data set to hopefully generate some SAR like speculation.
Date: April 9th 2024 Time: 2pm UK time other timezones
Place: https://ucl.zoom.us/j/91379419977
Recording: https://youtu.be/m4iSOV9m6s4?si=B2n-G0SuAZ3PpA6I
Previous Meeting: #108 Who can come?: Anyone. No need to say anything unless you'd like to.
Apologies:
Decks: Please @opensourceantibiotics/murligase remember that if you share slides/info, to drag and drop those into a comment on this page, below. Very easy and saves @mattodd having to pester you.
Agenda:
Key things today are:
i) Multi-targeting compounds identified from Warwick and Atomwise collections. Updates on any new IC50 or crystallographic or microbiology data.
ii) New data from Warwick on the contributed AZ compounds (retest at a lower concentration).
iii) Update on crystallographic data of AZ compound 4 (WYH9 compound) in Pae MurD ligase.
(please add if you'd like to prioritise anything)
1) Multi-targeting Compounds from the Warwick/NEU Enamine Collection and Atomwise Compounds
2) Multi-targeting Elaborated Fragments from Diamond Fragment Screen
3) Variants of AZ Compounds
These will include guanidinium and pyridinium derivatives to try to combat efflux.
4) New Protein Structures
No new structures to add to the PDB list.
5) De Novo Computational Modelling
@Yuhang-CADD has paused synthesis of @jhjensen2's originally-suggested compounds (last update was here while the AZ derivatives are being made.
6) CC4CARB Proposal (#93)
7) Misc/AOB
Last time @AJLloyd105 reported on the evaluation, enzymatically, of "double-headed" compounds containing uridine and ATP binders: . These were found to be binders and will be investigated further (need to upload deck). @AJLloyd105 to update as appropriate.
8) Mothballs (if no actions then these need to be linked in wiki and closed)
@mattodd is in the process of converting old items to the wiki
Next Meeting
May 14th 2pm UK time
L'esprit de l'escalier
If you'd like to follow up after the meeting, please comment below. You can also email, but please be clear if anything in the email should not be public domain - the default is always open.