Рибоциклиб

Описание

LEE011 is a cyclin-dependent kinase (CDK) inhibitor that targets cyclin D1/CDK4 and cyclin D3/CDK6 at nanomolar concentrations. It inhibits retinoblastoma protein phosphorylation, which prevents CDK-mediated G₁-S phase transition, arresting the cell cycle in the G₁ phase, suppressing DNA synthesis, and inhibiting cancer cell growth. LEE011 has been shown to reduce proliferation in 12 of 17 human neuroblastoma-derived cell lines by inducing cytostasis (mean IC₅₀ = 306 nM in sensitive lines).

Характеристики

Class: serine/threonine protein kinase
Treatment: Breast cancer
Oral bioavailability = 66%
Elimination half-life = 32 h
Protein binding = 70%

Использование

LEE 011 can be used in biological study of kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer.

Механизм действия

Ribociclib is a dual cdk4/cdk6 inhibitor. Induces G1 phase cell cycle arrest and senescence in neuroblastoma cell lines (IC50 = 306 nM). Delays tumor growth in vivo.