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Everything to do with Open Source Malaria Series 3
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UNC Kinome Scan #17

Open mbhebhe opened 5 years ago

mbhebhe commented 5 years ago

We sent OSM-S-106, 137 and 126 to UNC Chapel Hill (David Drewry) for a Kinome Scan. The preliminary results can be found on here.

image

OSM-S-106: Only 2 non-mutant human kinases with POC<10 at the 1 micromolar screening concentration (TYK2 and MAP3K19). A number of other kinases have POC<20. Interestingly, PfCDPK1 has POC=11, so perhaps a decent inhibitor.

OSM-S-137: WEE1 has POC= 0. My guess is that this is a false positive.

OSM-S-126: Data suggests this is a relatively narrow spectrum human FLT3 inhibitor.

They are currently doing the Kd determinations. The potentially potent and selective FLT3 compound is cool. They are intrigued by the TYK2 pseudokinase result. If the Kd confirms they would like to pursue this a little more carefully. (MHT (2/10/19): it has interesting biology, e.g. here and here, but, I think, no inhibitor?)

OSM-S-106: NC1=C2C(C=C(C3=CC(S(=O)(N)=O)=CC=C3)S2)=NC=N1 OSM-S-137: O=S(C1=CC(C2=CC3=NC=NC(N4CCN(CC5=CC=C(F)C=C5)CC4)=C3S2)=CC=C1)(N)=O OSM-S-126: C12=NC=NC(N3CCOCC3)=C1SC(C4=CC=CC=C4)=C2

MFernflower commented 5 years ago

possible new cancer drug on our hands? @mbhebhe @drc007

drc007 commented 5 years ago

@mbhebhe Can I just confirm the results. In the excel table in lab archive the structure of OSM-S-126 is drawn alongside the data for OSM-S-137.

OSM-S-137 has a POC of 75 against PfCDPK1 but also similar activity against 50 other kinases?

mbhebhe commented 5 years ago

@drc007 Thanks for pointing that out. I hadn't realised that the structures had been switched. I will contact them to confirm. With OSM-S-137's activity against PfCDPK1, I don't get what you mean

MFernflower commented 5 years ago

Once we verify structure and retest the morpholine compound perhaps could submit to a database or tool compound supplier like tocris @mbhebhe @drc007

MFernflower commented 5 years ago

Also interesting to note the left hand side of https://en.wikipedia.org/wiki/Quizartinib (FLT3 inhibitor in development) looks a tad bit like our morpholine compound! @mbhebhe @drc007 @mattodd

mattodd commented 3 years ago

Hi @Skame161 - here's the kinome scan I was mentioning. Compare and contrast with the predictive modelling that was done..?

Skame161 commented 3 years ago

@mattodd Thanks

Hi @mbhebhe -- Relatively new to the project and trying to get a handle on what the data means for which kinases OSM-S-106 is active against. Do we have a summary somewhere that I might have missed and do we know how these compare with which kinases came up in predictive modelling? Thanks and regards.

mbhebhe commented 3 years ago

Hi @Skame161 we only have the data that they gave us, they are in my ELN (https://au-mynotebook.labarchives.com/share/Tha%2520OSM%2520Series%25203/NTU2LjR8MjcwNjkvNDI4LTIwNjUvVHJlZU5vZGUvMzU3MTU3NzYxMHwxNDEyLjM5OTk5OTk5OTk5OTk=)

Skame161 commented 3 years ago

OK, thank you. I'll take a look.