Silatecan

Silatecan (AR-67) is a blood-brain barrier-permeable derivative of Camptothecin (HY-16560), DNA topoisomerase I inhibitor, an anticancer agent, and a radiosensitizer. Silatecan potently radiosensitizes wild-type p53 gliomas. Silatecan can be used in research related to glioma, leukemia, non-small cell lung cancer, colon cancer, ovarian cancer, renal cancer, prostate cancer, breast cancer, cervical cancer, gastric cancer, nasopharyngeal cancer, and uterine cancer^[1][2][3]. In Vitro:Silatecan (10 μg/mL; 0-6 h) exhibits better lactone stability in BALB/c mouse plasma than CPT-11 (HY-16562), Topotecan (HY-13768) and CPT (HY-16560), with a 50% degradation time of 30 min, and 20% of its lactone form remains after 6 h of incubation^[2].
Silatecan (at various concentrations; 72 h) potently inhibits the growth of multiple cancer cell lines, including drug-resistant sublines (e.g., gastric cancer MKN45, nasopharyngeal carcinoma TW-039)^[2].
Silatecan (0.001-10 μg/mL; 96 h) inhibits the proliferation of colorectal cancer SW480 cells, gastric cancer MKN45 cells, nasopharyngeal carcinoma TW039 cells, uterine cancer MES-SA cells, and Doxorubicin (HY-15142A)-resistant MES-SA/Dx5 cells in vitro tissue culture in a concentration-dependent manner, with IC₅₀ values ranging from 0.03 μM (TW039) to 2.21 μM (SW480)^[2].
Silatecan (0.1-1.0 μM; 30 min) potently radiosensitizes wild-type p53 glioma D54-MG cells by eliminating the shoulder region of radiation survival curves; its SER reaches 1.4 at concentrations of 0.1 or 0.2 μM^[3].
Silatecan (0.1 μM; 30 min) mildly radiosensitizes glioma T98G cells carrying mutant p53, with an SER of 1.2 at the concentration of 0.1 μM, but its sensitizing effect is weaker than that on D54-MG cells carrying wild-type p53^[3].
Silatecan (30 min) is a potent cytotoxic agent in wild-type TOP1 Chinese hamster lung fibroblast DC3F cells (LD₅₀ = 0.05 μM)^[3]. In Vivo:Silatecan (DB-67) (3-30 mg/kg/day; daily; 5 days to four 21-day cycles) dose-dependently inhibits subcutaneous U87 glioma xenograft growth in nude mice, with 30 mg/kg/day inducing complete tumor regression and no overt toxicity^[1].
Silatecan (3-10 mg/kg; i.v.; daily; two 5-consecutive-day cycles) exerts dose-dependent in vivo antitumor activity against subcutaneous human colorectal SW480 xenografts in male BALB/c nude mice, with significant tumor growth inhibition observed at 3 mg/kg and 10 mg/kg intravenous doses^[2].
Silatecan (3.3-10 mg/kg; i.v.; daily; two 5-consecutive-day cycles) exerts dose-dependent in vivo antitumor activity against subcutaneous gastric MKN45 xenografts in male BALB/c nude mice, with significant tumor growth inhibition observed at 3.3 mg/kg and 10 mg/kg intravenous doses^[2].