Dalpiciclib

Dalpiciclib (SHR-6390) is a highly selective, orally bioavailable CDK4/6 inhibitor with comparable potencies against CDK4 (IC50=12.4 nM) and CDK6 (IC50=9.9 nM). Dalpiciclib exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated tumor-suppressor retinoblastoma protein (Rb) and inducing G1 cell cycle arrest[1][2].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

CDK4:12.4 nM (IC50)

CDK6:9.9 nM (IC50)

Dalpiciclib (SHR-6390) (0-4 μM) inhibits cell proliferation in a dose-dependent manner[2]. Dalpiciclib (24 hours) significantly blocks phosphorylation of Rb at serine 780 in relative sensitive Eca 109 and KYSE-510 cell lines, but not in relative resistant Eca 9706 cell line.Dalpiciclib induces cell cycle arrest at G1 phase in Eca 109 and KYSE-510 cell lines[2]. Cell Proliferation Assay[2] Cell Line: Eca 109, Eca 9706, and KYSE-510 ESCC cell lines Concentration: 0-4 μM Incubation Time: 72  hours Result: Inhibited cell proliferation in a dose-dependent manner, with Eca 109 being the relative sensitive one and Eca 9706 being the relative resistant one.

Dalpiciclib (SHR-6390) (150 mg/kg; oral gavage; weekly for 3 weeks) shows antitumor activity against ESCC xenografts[2]. Dalpiciclib combines with Paclitaxel (PTX) or Cisplatin (CDDP) offered synergistic inhibitory effects in ESCC xenografts[2]. Animal Model: NOD/SCID mice (ESCC PDXs models) [2] Dosage: 150 mg/kg Administration: Oral gavage; weekly for 3 weeks Result: The growth of tumor was significantly suppressed in SHR6390 treatment group with various suppressions.

[1]. Zhang P, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res. 2021;9(1):24. Published 2021 Apr 12.

[2]. Wang J, et al. CDK4/6 inhibitor-SHR6390 exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated Rb and inducing G1 cell cycle arrest. J Transl Med. 2017;15(1):127. Published 2017 Jun 2.