Abemaciclib

China [CN]

I. Basic Information

Item | Details

English Name | Abemaciclib; Verzenio (trade name)

Chinese Name | Abemaciclib

CAS Number | 1231929-97-7

Chemical Name | N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[[4-fluoro-2-methyl-1-isopropyl-1H-benzimidazol-6-yl]amino]-2-pyrimidinecarboxamide

Molecular Formula | C₂₇H₃₀F₂N₈O

Molecular Weight | 506.58

Target | CDK4 (IC₅₀=2 nM), CDK6 (IC₅₀=10 nM)

Developer | Eli Lilly

Market Launch Date | September 2017 (US FDA); December 2020 (China NMPA)

Dosage Form and Strength | Film-coated tablets: 50mg, 100mg, 150mg, 200mg

II. Physicochemical Properties

Parameter | Data

Appearance | White to off-white crystalline powder

Solubility | Slightly soluble in water (approximately 0.01 mg/mL at pH 7.0), readily soluble in dimethyl sulfoxide (DMSO), N,N-dimethylformamide, soluble in methanol

Dissociation Constant (pKa) | 7.3 (pyridine ring), 5.6 (amino group) (measured values)

Stability | Stable for 24 months at 25℃/60% RH, stored in a sealed, cool, and dry place (20-25℃), avoiding high temperature, light, and moisture

Chiral Characteristics | Contains 1 chiral center (isopropyl position), single R-configuration, optical purity >99.5%

Partition Coefficient (logP) | 4.3 (predicted value)

III. Mechanism of Action

Abemaciclib selectively inhibits CDK4/6, blocking the cell cycle transition from G1 phase to S phase, thereby inhibiting tumor cell proliferation. Core mechanism and characteristics:

Binding CDK4/6 inhibitors bind to the ATP binding site of CDK4/6, inhibiting its complex formation with cyclin D and preventing the phosphorylation of retinoblastoma protein (Rb).

The inhibited phosphorylation of Rb prevents the release of transcription factor E2F, causing tumor cells to arrest in the G1 phase and preventing them from entering the S phase for DNA replication, ultimately inhibiting proliferation.

The selectivity for CDK4/6 is significantly higher than for other CDK subtypes (such as CDK1/2/5), resulting in fewer off-target effects and improved safety.

It can cross the blood-brain barrier, offering potential therapeutic value for patients with breast cancer brain metastases.

IV. Clinical Applications