TIC10

SKU: orb1222637

Description

TIC10 inactivates Akt and ERK to induce TRAIL through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. Phase 1/2.(In Vitro):Dordaviprone transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier.Dordaviprone induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of Dordaviprone.Dordaviprone 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.Dordaviprone 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.Dordaviprone also causes a down-regulation of the total expression of ERK.\n(In Vivo):In DLD-1 colon cancer xenografts, Dordaviprone induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progress after a single dose. A single dose of Dordaviprone 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 Dordaviprone. Titration of a single oral dose of Dordaviprone in the HCT116 xenograft model reveals sustained antitumor efficacy at 25 mg/kg. Exposure to oral Dordaviprone 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 Dordaviprone significantly (P=0.00789) prolongs the survival of these mice by 4 weeks.

Key Properties

• CAS Number: 1616632-77-9
• MW: 386.49
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₆N₄O
• SMILES: CC1=CC=CC=C1CN1C2=NCCN2C2=C(CN(CC3=CC=CC=C3)CC2)C1=O
• Target: TRAIL
• Solubility: DMSO : 33.33 mg/mL 86.24 mM

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ONC-201

Quick Database Links

Gene Symbol

TRAIL