Abemaciclib

Abemaciclib (LY2835219) is a selective and BBB-permeable CDK4/6 inhibitor with IC₅₀ values of 2 nM and 10 nM for CDK4 and CDK6, respectively. IC50 & Target:IC50: 2 nM (CDK4), 10 nM (CDK6)^[3] In Vitro:Abemaciclib reduces cell viability with the IC₅₀ values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells^[1]. Abemaciclib shows inhibition on A375R1-4, M14R, and SH4R with EC₅₀ values ranging from 0.3 to 0.6 μM; Abemaciclib inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC₅₀ values of 395, 260, and 463 nM, respectively^[2]. Abemaciclib inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells^[3]. In Vivo:Abemaciclib (45 mg/kg, p.o.) in combination with RAD001 causes a cooperative antitumor effect in HNSCC xenograft tumor^[1]. Abemaciclib (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model^[2].