Абемациклиб

Характеристики

Class: serine/threonine protein kinase
Treatment: Breast cancer
Oral bioavailability = 46%
Elimination half-life = 18 h
Protein binding = 95–98%

Биохимия/физиол Действия

LY2835219 (abemaciclib) was identified via compound and biochemical screening by scientists at Eli Lilly and Company Research Laboratories and selected for its biological activity and highly selective inhibition of the complexes CDK4/ cyclin D1 (IC50 =2 nmol/L) and CDK6/cyclin D1 (IC50 =10 nmol/L), with no activity against other CDK/cyclin complexes or cell-cycle-related kinases within the nanomolar ranges, except for inhibition of CDK9 at IC50 at least five times higher. The compound was shown to act as a competitive inhibitor of the ATP-binding domain of the CDK4 and CDK6 and to be 14 times more potent against CDK4 than against CDK6. In comparison to palbociclib and ribociclib, abemaciclib shows higher selectivity for the complex CDK4/cyclin D1, with IC50 values five times lower than those of the two other compounds[1].

Ферментативный ингибитор

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.