TIC10 (ONC-201) is a potent, orally active, and stable tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)inducer which acts by inhibitingAktandERK, consequently activating Foxo3a and significantly inducing cell surface TRAIL. TIC10 can cross the blood-brain barrier^[1].

TIC10 transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier^[1].
TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10^[1].
TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription^[1].
TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their micro-environment to enhance the concentrations of the endogenous tumor suppressor TRAIL^[1].
TIC10 also causes a down-regulation of the total expression of ERK^[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].

386.49

Solid

C₂₄H₂₆N₄O

1616632-77-9

Room temperature in continental US; may vary elsewhere.

DMSO : 9.38 mg/mL(24.27 mM;ultrasonic and warming and heat to 60℃)

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