TIC10

• CAT Number: I002065
• CAS Number: 1616632-77-9
• Molecular Formula: C24H26N4O
• Molecular Weight: 386.5
• Purity: ≥95%
• Target: Akt; ERK
• Solubility: 10 mM in DMSO
• Storage: -20°C
• InChIKey: VLULRUCCHYVXOH-UHFFFAOYSA-N

TIC10(ONC-201) is a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier.IC50 Value:Target: Akt; ERKTIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. 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. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL [1].http://onlinelibrary.wiley.com/doi/10.1002/anie.201402133/abstract

Reference

1:Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells. Cheng L, Liu YY, Lu PH, Peng Y, Yuan Q, Gu XS, Jin Y, Chen MB, Bai XM.Oncotarget. 2017 Apr 25;8(17):28385-28394. doi: 10.18632/oncotarget.16073. PMID: 28415690 Free Article2:The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent. Zhang Q, Wang H, Ran L, Zhang Z, Jiang R.Biochem Biophys Res Commun. 2016 Aug 5;476(4):260-6. doi: 10.1016/j.bbrc.2016.05.106. Epub 2016 May 24. PMID: 27233611 3:TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Karpel-Massler G, Bâ M, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD.Oncotarget. 2015 Nov 3;6(34):36456-71. doi: 10.18632/oncotarget.5505. PMID: 26474387 Free PMC Article4:Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, El-Deiry WS.Mol Cancer. 2015 May 1;14:99. doi: 10.1186/s12943-015-0346-9. PMID: 25927855 Free PMC Article5:TIC10/ONC201: a bend in the road to clinical development. Greer YE, Lipkowitz S.Oncoscience. 2015 Feb 20;2(2):75-6. eCollection 2015. No abstract available. PMID: 25859547 Free PMC Article6:Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner. Prabhu VV, Allen JE, Dicker DT, El-Deiry WS.Cancer Res. 2015 Apr 1;75(7):1423-32. doi: 10.1158/0008-5472.CAN-13-3451. Epub 2015 Feb 20. PMID: 25712124 Free PMC Article7:Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10. Allen JE, Prabhu VV, Talekar M, van den Heuvel AP, Lim B, Dicker DT, Fritz JL, Beck A, El-Deiry WS.Cancer Res. 2015 Apr 15;75(8):1668-74. doi: 10.1158/0008-5472.CAN-14-2356. Epub 2015 Feb 13. PMID: 25681273 Free PMC Article8:Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W, Zhou JY, Wu GS, El-Deiry WS.Sci Transl Med. 2013 Feb 6;5(171):171ra17. doi: 10.1126/scitranslmed.3004828. PMID: 23390247 Free PMC Article