| Identification | Back Directory | [Name]
2-Quinoxalinamine, N,N-diethyl-7-[5-fluoro-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-4-pyrimidinyl]- | [CAS]
2677026-14-9 | [Synonyms]
CDK6/PIM1-IN-1
2-Quinoxalinamine, N,N-diethyl-7-[5-fluoro-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-4-pyrimidinyl]- | [Molecular Formula]
C25H28FN9 | [MOL File]
2677026-14-9.mol | [Molecular Weight]
473.55 |
| Hazard Information | Back Directory | [Uses]
CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor with IC50?values of 39 and 88 nM, respectively.?CDK6/PIM1-IN-1 inhibits CDK4 (IC50=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity[1]. | [in vivo]
CDK6/PIM1-IN-1 (compound 51; orally; 60, 90 mg/kg/day; 17 days) displays more potent antitumor activity?in BALB/c mice with K562 cell lines[1].
CDK6/PIM1-IN-1 (iv; 5 mg/kg) has the t1/2, MRT0-∞, and AUC0-∞?values of 9.78 h, 14.61 h, and 1153.74 h·ng/mL, respectively in Sprague–Dawley (SD) rats[1].
CDK6/PIM1-IN-1 (po; 5 mg/kg) has the?t1/2, Tmax, Cmax, and AUC0-∞ of 15.81 h, 11 h, 152.31 ng/mL, and 5152.92 h·ng/mL, respectively in SD rats[1].
| [IC 50]
CDK6/cyclinD1: 39 nM (IC50); CDK1/cyclinB: >10 μM (IC50); CDK2/cyclinA: 2.274 μM (IC50); CDK3/Cyclin E: >10 μM (IC50); Cdk4/cyclin D1: 3.6 nM (IC50); Cdk5/p25: >10 μM (IC50); CDK7/Cyclin H/MNAT1: 393 nM (IC50); CDK9/cyclinT1: 440 nM (IC50); CDK12/Cyclin K: >10 μM (IC50); CDK13/Cyclin K: >10 μM (IC50); PIM1: 88 nM (IC50); PIM2: >10 μM (IC50); PIM3: 92 nM (IC50) | [References]
[1] Kai Yuan, et al. Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia. J Med Chem. 2022 Jan 13;65(1):857-875. DOI:10.1021/acs.jmedchem.1c02019 |
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