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Biological Activity:

AG-120 (Ivosidenib) is a potent, selective and reversible inhibitor of IDH1 with IC50 < 100 nM. It has been shown to lower 2-HG levels and restore cellular differentiation in IDH1-mutant primary human blast cells cultured ex vivo. In phase I clinical trials targeting patients with IDH1-mutated, relapsed and/or refractory (R/R) AML or untreated AML not eligible for standard of care or R/R MDS, AG-120 is well tolerated to date (10/2015) and MTD was not reached. Overall response rate is 35% including 12 CRs.

How to Use:

In vitro: AG-120 was used at 1 μM in vitro and cellular assays.
In vivo: AG-120 was dosed orally to mice bearing IDH1 mutant tumors at 150 mg/Kg once per day.

Reference:

• 1. Erica Hansen, et al. AG-120, an Oral, Selective, First-in-Class, Potent Inhibitor of Mutant IDH1, Reduces Intracellular 2HG and Induces Cellular Differentiation in TF-1 R132H Cells and Primary Human IDH1 Mutant AML Patient Samples Treated Ex Vivo. (2014) Blood. 124:3734
• 2. Kc B, et al. Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120. (2016) Clin Lymphoma Myeloma Leuk. In press.