| Identification | Back Directory | [Name]
1(2H)-Isoquinolinone, 2-ethyl-6-[5-fluoro-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-4-pyrimidinyl]-3,4-dihydro-, hydrochloride (1:1) | [CAS]
2699091-15-9 | [Synonyms]
CDK4/6-IN-14
1(2H)-Isoquinolinone, 2-ethyl-6-[5-fluoro-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-4-pyrimidinyl]-3,4-dihydro-, hydrochloride (1:1) | [Molecular Formula]
C24H27ClFN7O | [MOL File]
2699091-15-9.mol | [Molecular Weight]
483.98 |
| Hazard Information | Back Directory | [Uses]
CDK4/6-IN-14 is a potent and highly selective CDK4 and CDK6 (CDK) inhibitor with IC50s of 10 nM and 16 nM, respectively. CDK4/6-IN-14 exhibits more than 60-fold selectivity over CDKs 1, 2, 7, and 9, and shows high selectivity among other 205 kinases[1]. | [in vivo]
CDK4/6-IN-14 (compound 42; 100-150 mg/kg; p.o; once a day; for 23 days) significantly inhibits tumor growth of the MCF-7 xenograft model[1].
CDK4/6-IN-14 (compound 42) exhibits a suitable t1/2 of intravenous and oral administration (2.62 and 3.59 h, respectively). Moreover, the oral bioavailability of CDK4/6-IN-14 is 43%[1].
Pharmacokinetic Parameters of CDK4/6-IN-14 (Compound 42) in Sprague–Dawley Rats[1].
| admin. | Cmax (ng/mL) | AUC0-∞ (h × ng/mL) | MRT0-∞ (h) | Tmax (h) | t1/2 (h) | F (%) | | IV | 290.52 | 372.56 | 3.50 | 0.033 | 2.62 | | | PO | 144.11 | 1612.18 | 9.11 | 6 | 3.59 | 43 |
Dose: i.v. at 1 mg/kg; p.o. at 10 mg/kg [1]| Animal Model: | BALB/c nude mice bearing MCF-7 cells[1] | | Dosage: | 100 mg/kg, 150 mg/kg
| | Administration: | Orally administertion; once a day; for 23 days | | Result: | Significantly inhibited tumor growth of the MCF-7 xenograft model. |
| [IC 50]
CDK4: 10 nM (IC50); CDK6: 16 nM (IC50); CDK1: >10000 nM (IC50); CDK2: 1045 nM (IC50); CDK7: 2595 nM (IC50); CDK9: 2664 nM (IC50) | [References]
[1] Weijiao Chen, et al. Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer. J Med Chem. 2022 Nov 24;65(22):15102-15122. DOI:10.1021/acs.jmedchem.2c00947 |
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