Pharmacometrics Ltd, 51 North Road, Whittlesford, Cambridge CB22 4NZ, UK +44 1382 206062 ; +44 1382 206067 ;
Expert Opin Drug Discov. 2008 Jan;3(1):131-43. doi: 10.1517/17460441.3.1.131.
Seliciclib is an inhibitor of cyclin-dependent kinases 2, 7 and 9. Its primary mechanism of action is the inhibition of transcription, resulting in the selective downregulation of rapidly cycling mRNA transcripts, including Mcl-1 and cyclin D1. It possesses antitumour activity as a single agent and also synergises with a wide range of cytotoxic and targeted drugs. Seliciclib has high oral bioavailability and is in clinical development in a capsule formulation. The clinical dose has been determined in Phase I clinical trials for schedules of 3 - 10 consecutive days per cycle of 2 or 3 weeks duration. Its major clinical toxicities include nausea, vomiting, asthenia, hypokalaemia, elevation of creatinine levels and liver function tests, which are reversible after cessation of dosing. Seliciclib is non-myelosuppressive and does not cause intestinal toxicity. Phase II trials have commenced in non-small cell lung cancer and will be initiated shortly in nasopharyngeal carcinoma.
塞利昔布是细胞周期蛋白依赖性激酶 2、7 和 9 的抑制剂。其主要作用机制是抑制转录，导致快速循环的 mRNA 转录物的选择性下调，包括 Mcl-1 和 cyclin D1。它作为单一药物具有抗肿瘤活性，并且与广泛的细胞毒性和靶向药物具有协同作用。塞利昔布具有较高的口服生物利用度，正在胶囊制剂中进行临床开发。临床剂量已在 I 期临床试验中确定，方案为每 2 或 3 周为一个周期，连续 3-10 天。其主要临床毒性包括恶心、呕吐、乏力、低钾血症、肌酐和肝功能试验升高，停药后可逆转。塞利昔布无骨髓抑制作用，不会引起肠道毒性。非小细胞肺癌的 II 期临床试验已经开始，鼻咽癌的试验即将开始。
