Amsilarotene 是口服有活性的合成类视黄醇，对视黄酸受体 α (RAR-α) 具有选择性亲和力，对 RAR-α 和 RAR-β 的Ki=为 2.4 nM 和 400 nM。它可造成人胃癌、卵巢癌细胞及肝细胞癌的凋亡，可用于研究癌症。

Amsilarotene inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

Preclinical models have shown that Amsilarotene(4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has antitumor activity in hepatocellular carcinoma (HCC).

We conducted a phase I study in Japanese patients with advanced HCC to examine the pharmacokinetics, recommended dose, safety, and efficacy of Amsilarotene. The administered dose of Amsilarotene was 10 mg/day in four patients (level 1), 20 mg/day in six (level 2), and 30 mg/day in three (level 3). There was no dose-limiting toxicity at level 1. Only one patient each had dose-limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level 3 (30 mg/day) was considered the maximum tolerated dose and 20 mg/day the recommended dose by a panel of medical experts, placing maximum emphasis on safety. The most frequent adverse events were fatigue, headache, and dermal symptoms such as rash. Pharmacokinetic parameters in Japanese patients with HCC were similar to those in patients in the United States, most of whom were Caucasian. Although no patient had a complete or partial response, the disease control rate was 38.5%. In conclusion, the recommended dose of Amsilarotene for patients with HCC is 20 mg/day. Amsilarotene had an acceptable toxicity profile, warranting further evaluation in clinical trials.

125973-56-0

C20H27NO3Si2

385.6

TAC 101;TAC101;TAC-101;Amsilarotene

H2O:Insoluble
H2O:Insoluble
DMSO:60 mg/ml (155.6 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years