1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-(dimethylamino)-ethanone

CHMFL-FLT3-122 is a potent and orally available FLT3 kinase inhibitor for FLT3-ITD positive acute myeloid leukemia. In vivo CHMFL-FLT3-122 significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (50 mg/kg) without exhibiting obvious toxicity.

CHMFL-FLT3-122 is a potent, selective and orally active FLT3 kinase with an IC50 of 40 nM. CHMFL-FLT3-122 shows selectivity for FLT3 over BTK (IC50 of 421 nM) and c-KIT (IC50 of 559 nM) kinases. CHMFL-FLT3-122 induces apoptosis by arresting the cell cycle into the G0/G1 phase[1].

[1] Xixiang Li, et al. Discovery of (R)-1-(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-2-(dimethylamino)ethanone (CHMFL-FLT3-122) as a Potent and Orally Available FLT3 Kinase Inhibitor for FLT3-ITD Positive Acute Myeloid Leukemia. J Med Chem. 2015 Dec 24;58(24):9625-38. DOI:10.1021/acs.jmedchem.5b01611