Compounds for hERG Evaluation Round 2

OpenSourceMalaria / Series4

Repository for Series 4 of the Open Source Malaria Consortium

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Compounds for hERG Evaluation Round 2 #63

Open edwintse opened 5 years ago

edwintse commented 5 years ago

Following the hERG results we got for select compounds in April (#37), we will be wanting to run a second round of compounds in preparation for the upcoming paper. This set should consist of:

Compounds from the original hERG assay by AstraZeneca in 2014 for verification of these results (one from each hERG binding, non-binding and in-between).
One compound from the previous set to make sure the results are consistent (most likely MMV897698)
One or two compounds from the OHOH set (MMV1581295 and maybe one other)
Possibly the extended OHOH compound recently made by @maratsydney and sent for potency evaluation (#62)

herg round 2

Are they any other suggestions for compounds to include in this set? There should be a max of 9 compounds that can be run in one well plate.

hERG round 2 chemdraw.zip

MFernflower commented 5 years ago

Has any progress been made on this - i.e have any compounds been shipped @edwintse

edwintse commented 5 years ago

@MFernflower Not yet. Likely in the new year, along with getting the metabolic clearance data for the OHOH compound.

mattodd commented 5 years ago

I guess the final list here will depend a little on whether you're going to prioritise the synthesis of further carb acids, right @edwintse i.e. to try to improve potency of the compound that gave super low inhibition (OSM-S-515). Or do you think we should be shipping a set of the above, and then later shipping any other analogs of the carboxylic acid? (link to this discussion installed on wiki).

MFernflower commented 5 years ago

The methyl and ethyl esters of the acid test perhaps? I do not really know much about the sar of this off target to be honest tho

@edwintse

edwintse commented 5 years ago

@mattodd Considering that all the above compounds are in Sydney, I think it would be best to ship them first. The acid derivatives I make here will be shipped separately anyway so better not to wait.

@MFernflower Yes, I was told by someone at a conference who made acid compounds for hERG that esters can help with regaining the potency. I'll try this after I make the rest of the derivatives.

MFernflower commented 5 years ago

@edwintse Has your ELN changed by any chance? Just curious