TIC10 (Synonyms: ONC-201) TIC10 是一种有效,有口服活性,稳定的肿瘤坏死因子相关的凋亡诱导配体 TRAIL 诱导剂,其通过抑制 Akt 和 ERK 起作用,从而激活 Foxo3a 并显着诱导细胞表面 TRAIL。TIC10 可透过血脑屏障。
TIC10 transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier[1]. In DLD-1 colon cancer xenografts, TIC10 induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progress after a single dose. A single dose of TIC10 also induces a sustained regression of the SW480 xenograft and is equally effective when delivered by intraperitoneal or oral route, suggesting favorable oral bioavailability for TIC10. Titration of a single oral dose of TIC10 in the HCT116 xenograft model reveals sustained antitumor efficacy at 25 mg/kg. Exposure to oral TIC10 at 25 mg/kg weekly for 4 weeks in immunocompetent mice does not cause any changes in selected serum chemistry markers. The same oral dosing schedule is applied to Eμ-myc transgenic mice, which spontaneously develop meta-static lymphoma from weeks 9 to 12 of age, and TIC10 significantly (P=0.00789) prolongs the survival of these mice by 4 weeks[1]. |