GSK321 (C09-1134-756)

GSK321 is a potent inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) enzymes . GSK321 has high inhibitory and selectivity for mutant IDH1 enzymes. GSK321 can be used for the research of acute myeloid leukemiaIn VitroGSK321 has high inhibitory for mutant IDH1 enzymes, with IC 50 values of 4.6 nM against R132H, 3.8 nM against R132C and 2.9 nM against R132G, respectively. GSK321 (0, 0.5, 5 μM; 48 h) induces markedly decreased H3K9me2 levels. GSK321 decreases intracellular 2-HG and affects proliferation of primary IDH1 mutant AML cells. GSK321 has inhibition activity for mutant IDH1 that overcomes the pathognomonic differentiation block of AML cells, and induces myeloid differentiation of IDH1 mutant cells at the level of leukemic blasts and more stem-like cells. GSK321 leads to genome-wide DNA cytosine hypomethylation in IDH1-mutant AML cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: HT-1080 cells Concentration: 0, 0.5, 5 μM Incubation Time: 48 h Result: Lead to the reduction of histone H3K9 dimethylation (H3K9me2). Cell Proliferation AssayCell Line: IDH1 mutant AML cells Concentration: 3 μM Incubation Time: 15 days Result: Showed a significant, initial increase in cell numbers (2-fold to 15-fold) in IDH1 mutant AML cells. Cell Cycle AnalysisCell Line: IDH1 mutant AML cells Concentration: Incubation Time: 7 days Result: Observed a reproducible and significant decrease in quiescent (G0)-phase cells in R132G IDH1 and R132C IDH1 AML cells.Form:SolidIC50& Target:IC50 for mutant IDH1 enzymes: 4.6 nM (R132H), 3.8 nM (R132C), 2.9 nM (R132G). Specification: 0.99 Molecular Formula: C28H28FN5O3 Molecular Weight: 501.55 PubChem CID: 91864709 Isomeric SMILES: C[C@@H]1CN(CC2=C1N(N=C2C(=O)NC3=CC=CC(=C3)[C@H](C)O)CC4=CC=C(C=C4)F)C(=O)C5=CC=CN5