| Identification | Back Directory | [Name]
Pyrido[2,3-d]pyrimidin-7(8H)-one, 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-piperidinyl)-2-pyridinyl]amino]- | [CAS]
1637781-04-4 | [Synonyms]
SHR-6390
Dalpiciclib (Synonyms: SHR-6390)
Pyrido[2,3-d]pyrimidin-7(8H)-one, 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-piperidinyl)-2-pyridinyl]amino]- | [Molecular Formula]
C25H30N6O2 | [MDL Number]
MFCD34567203 | [MOL File]
1637781-04-4.mol | [Molecular Weight]
446.54 |
| Chemical Properties | Back Directory | [Boiling point ]
674.3±65.0 °C(Predicted) | [density ]
1.277±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
9.96±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
Dalpiciclib (SHR-6390) is an orally active and highly selective inhibitor of CDK4 and 6 with IC50 values of 12.4 nM and 9.9 nM, respectively[1][2]. Dalpiciclib shows antitumor activity against breast cancer and esophageal squamous cell carcinoma[1][2][3][4]. | [in vivo]
Dalpiciclib (oral gavage; 150 mg/kg; once weekly; 3 weeks) shows antitumor activity against ESCC xenografts[3].
Dalpiciclib combined with Paclitaxel (PTX) or Cisplatin (CDDP) offer synergistic inhibitory effects in ESCC xenografts[3].
Dalpiciclib (oral gavage; 37.5 mg/kg, 75 mg/kg, 150 mg/kg; once daily; 30 days) shows antitumor activity in human xenograft models [4]. | Animal Model: | NOD/SCID mice (ESCC PDXs models) [3] | | Dosage: | 150 mg/kg | | Administration: | Oral gavage; 150 mg/kg; once weekly; 3 weeks | | Result: | Suppressed the growth of tumor. |
| Animal Model: | 5-week-old female Balb/cA-nude mice subcutaneously inoculated MCF7/ARO, COLO 205 and U87MG[4] | | Dosage: | 37.5 mg/kg, 75 mg/kg, 150 mg/kg | | Administration: | Oral gavage; 37.5 mg/kg, 75 mg/kg, 150 mg/kg; once daily; 30 days | | Result: | Caused regression of all tumor xenografts at the highest dose tested. |
| [IC 50]
CDK4: 12.4 nM (IC50); CDK6: 9.9 nM (IC50) | [References]
[1] Jose Manuel Perez-Garcia, et al. Perez-Garcia JM, Cortes J, Llombart-Cussac A. CDK4/6 inhibitors in breast cancer: spotting the difference. Nat Med. 2021 Nov;27(11):1868-1869. DOI:10.1038/s41591-021-01570-9
[2] Pin Zhang, 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 Apr 12;9(1):24. DOI:10.1186/s40364-021-00271-2
[3] Jiayuan Wang, 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 Jun 2;15(1):127. DOI:10.1186/s12967-017-1231-7
[4] Fei Long, et al. Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models. Cancer Sci. 2019 Apr;110(4):1420-1430. DOI:10.1111/cas.13957 |
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