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AGI-6780 is the first highly potent and selective small molecule inhibitor of mutant IDH2, which binds in an allosteric manner at the dimer interface of mutant IDH2-R140Q.  It inhibits IDH2-R140Q in vitro with an IC₅₀ ~23 nM and inhibits 2-HG formation in human glioblastoma U87 and TF-1 cells expressing IDH2-R140Q with IC₅₀ < 20 nM. AGI-6780 can reverse the differentiation blockade in TF-1 cells conferred by IDH2-R140Q, and induce blast differentiation in primary human IDH2-R140Q AML patient samples. It provides proof-of-concept that inhibitors targeting mutant IDH2-R140Q could have potential applications as a differentiation therapy for cancer. 

How to Use:

In vitro:  AGI-6780 was suggested to be used at 1-5 µM final concentration in vitro.

In vivo:  n/a

Reference:

1. 1. Fang Wang, et al. Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation. (2013) Science. 340(6132):622-6.

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