Milciclib

802539-81-7

C25H32N8O

DMSO : 20 mg/mL (43.42 mM; Need ultrasonic)

Cell Cycle/DNA Damage; Autophagy

Milciclib (PHA-848125) is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC₅₀s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively. IC50 & Target: IC50: 45 nM (cyclin A/CDK2), 150 nM (cyclin H/CDK7), 160 nM (cyclin D1/CDK4), 363 nM (cyclin E/CDK2), 398 nM (cyclin B/CDK1)^[1], 53 nM (TRKA)^[2] In Vitro: Milciclib (PHA-848125; 0.156 or 0.625 uM) up-regulates the expression of PDCD4, DDIT4, SESN2/sestrin 2 and DEPDC6/DEPTOR in GL-Mel cells^[1]. Milciclib (PHA-848125) potently inhibits the kinase activity of CDK2/cyclin A complex and of TRKA in a biochemical assay, with IC₅₀s of 45 and 53 nM, respectively. Milciclib induces a clear accumulation of cells in G1 phase. Milciclib strongly inhibits NGF-induced phosphorylation of TRKA in a dose-dependent manner^[2]. In Vivo: Milciclib (PHA-848125; 5, 10, and 15 mg/kg, p.o.) inhibits the growth of tumor in 7, 12-dimethylbenz(a) anthracene (DMBA)-induced rat mammary carcinoma model. Milciclib has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation^[2]. Milciclib (PHA-848125; 40 mg/kg) induces a significant tumor growth inhibition in K-Ras^G12DLA2 mice, and this is accompanied by a reduction in the cell membrane turnover^[3].