ONC-201 (TIC-10)
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MedKoo CAT#: 206124

CAS#: 1616632-77-9

Description: ONC-201, also known as TIC10, is a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 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.


Price and Availability

Size
Price

25mg
USD 150
1g
USD 1950
Size
Price

100mg
USD 450
2g
USD 2750
Size
Price

500mg
USD 1250
5g
USD 3650

ONC201, purity > 98%, is in stock. The same day shipping out after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international). Note: the estimated shipping out time for order > 2g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206124
Name: ONC-201 (TIC-10)
CAS#: 1616632-77-9
Chemical Formula: C24H26N4O
Exact Mass: 386.21066
Molecular Weight: 386.48944
Elemental Analysis: C, 74.58; H, 6.78; N, 14.50; O, 4.14


Synonym: ONC201; ONC 201; ONC-201; NSC350625; NSC-350625; NSC 350625; TIC10; TIC 10; TIC-10; TRAIL inducing compound 10.

IUPAC/Chemical Name: 7-benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one

InChi Key: VLULRUCCHYVXOH-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-23(29)21-17-26(15-19-8-3-2-4-9-19)13-11-22(21)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3

SMILES Code: O=C1N(CC2=CC=CC=C2C)C3=NCCN3C4=C1CN(CC5=CC=CC=C5)CC4


Technical Data

Appearance:
White to off-white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not soluble in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
TIC10 is not water soluble, may be dissolved in DMSO, then is formulated in 20% Cremophor EL, 10% DMSO, and 70% PBS buffer.

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

ONC-201 is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) and extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon administration, Akt/ERK inhibitor ONC201 binds to and inhibits the activity of Akt and ERK, which may result in inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway as well as the mitogen-activated protein kinase (MAPK)/ERK-mediated pathway. This may lead to the induction of tumor cell apoptosis mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/TRAIL death receptor type 5 (DR5) signaling in AKT/ERK-overexpressing tumor cells. The PI3K/Akt signaling pathway and MAPK/ERK pathway are upregulated in a variety of tumor cell types and play a key role in tumor cell proliferation, differentiation and survival by inhibiting apoptosis. In addition, ONC201 is able to cross the blood-brain barrier.


References

1: Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, El-Deiry WS. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015 May 1;14(1):99. doi: 10.1186/s12943-015-0346-9. PubMed PMID: 25927855; PubMed Central PMCID: PMC4428111.

2: Greer YE, Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015 Feb 20;2(2):75-6. eCollection 2015. PubMed PMID: 25859547; PubMed Central PMCID: PMC4381697.

3: Prabhu VV, Allen JE, Dicker DT, El-Deiry WS. Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner. Cancer Res. 2015 Apr 1;75(7):1423-32. doi: 10.1158/0008-5472.CAN-13-3451. Epub 2015 Feb 20. PubMed PMID: 25712124.

4: Allen JE, Prabhu VV, Talekar M, van den Heuvel AP, Lim B, Dicker DT, Fritz JL, Beck A, El-Deiry WS. 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. Cancer Res. 2015 Apr 15;75(8):1668-74. doi: 10.1158/0008-5472.CAN-14-2356. Epub 2015 Feb 13. PubMed PMID: 25681273.

5: Wagner J, Kline CL, Pottorf RS, Nallaganchu BR, Olson GL, Dicker DT, Allen JE, El-Deiry WS. The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity. Oncotarget. 2014 Dec 30;5(24):12728-37. PubMed PMID: 25587031; PubMed Central PMCID: PMC4350349.

6: Jacob NT, Lockner JW, Kravchenko VV, Janda KD. Pharmacophore reassignment for induction of the immunosurveillance cytokine TRAIL. Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6628-31. doi: 10.1002/anie.201402133. Epub 2014 May 18. PubMed PMID: 24838721.

7: 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. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013 Feb 6;5(171):171ra17. doi: 10.1126/scitranslmed.3004828. PubMed PMID: 23390247.

(Last updated: 4/20/2016)