Uses
N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine is an CDK4/6 protein kinase inhibitor with potential antitumor
effects.
Uses
LY2835219 is an orally-bioavailable dual inhibitor of cyclin-dependent kinase 4 (CDK4) and CDK6 (IC50s = 2 and 10 nM, respectively). Through this mechanism, it blocks phosphorylation of retinoblastoma protein, resulting in arrest of cell cycling in the G1 phase. LY2835219 has antitumor action against xenografts when used alone or in combination with other chemotherapeutic compounds.[Cayman Chemical]
Description
Abemaciclib (1231930-82-7) is a potent and selective CDK4/6 inhibitor (IC50?= 2 nM and 10 nM respectively).1?It caused G1 cell cycle arrest in colo-205 colorectal cells, MDA-MB-361 breast cancer cells, and MV4-11 AML cells. Abemaciclib was also active in several human tumor xenograft models. It displayed efficacy in patients with various solid tumors including breast cancer, non-small cell lung cancer. Glioblastoma, melanoma, colorectal cancer, and hormone receptor-positive breast cancer.2?Abemaciclib induced a T cell inflamed tumor microenvironment and enhanced the efficacy of PD-L1 checkpoint blockade in MCF-7 breast cancer cells.3?FDA approved for the treatment of advanced breast cancers.
Enzyme inhibitor
This oral cell cycle inhibitor (FWfree-base = 506.61 g/mol; FWmesylate-salt = 602.70 g/mol; CAS 1231930-82-7 (mesylate salt)), also known as LY2835219 and N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5- fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2- pyrimidinamine, targets the cyclin-dependent kinase CDK4, or cyclin D1 (IC50 = 2 nM) and CDK6, or cyclin D3 (IC50 = 6 nM), inhibiting retinoblastoma (Rb) protein phosphorylation in early G1, thereby arresting the cell cycle in the G1, suppressing DNA synthesis, and inhibiting cancer cell growth. LY2835219 inhibits activation of AKT and ERK, but not mTOR.
in vivo
Abemaciclib (LY2835219) (45 mg/kg, p.o.) in combination with RAD001 causes a cooperative antitumor effect in HNSCC xenograft tumor[1].
Abemaciclib (LY2835219) (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model[2].
IC 50
Cdk4/cyclin D1: 2 nM (IC50); CDK6/cyclinD1: 10 nM (IC50); CDK9/cyclinT1: 57 nM (IC50); CDK5/p35: 287 nM (IC50); Cdk5/p25: 355 nM (IC50); CDK2/cyclinE: 504 nM (IC50); CDK1/cyclinB1: 1627 nM (IC50); CDK7/Mat1/cyclinH1: 3910 nM (IC50); PIM1: 50 nM (IC50); PIM2: 3400 nM (IC50); HIPK2: 31 nM (IC50); DYRK2: 61 nM (IC50); CK2: 117 nM (IC50); GSK3b: 192 nM (IC50); JNK3: 389 nM (IC50); FLT3 (D835Y): 403 nM (IC50); DRAK1: 659 nM (IC50); FLT3: 3960 nM (IC50)
