WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406252
CAS#: 41276-02-2 (TIC10 isomer)
Description: TIC10 isomer is an isomer and the "inactive version" of TIC10. TIC-10 isomer was introduced to the research community since it was structurally wrong-assigned as the bioactive TIC-10 during early stage development of TIC-10 (now called ONC-201). TIC-10 isomer was found to be inactive, which did not reduce the viability of cancer cells. TIC-10 isomer may be used as a reference compound to compare with ONC-201.
MedKoo Cat#: 406252
Name: TIC-10 Isomer
CAS#: 41276-02-2 (TIC10 isomer)
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: TIC10 isomer; TIC 10 isomer; TIC10 isomer; ONC201 isomer; ONC 201 isomer; ONC201 isomer.
IUPAC/Chemical Name: 7-benzyl-10-(2-methylbenzyl)-2,3,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[4,3-d]pyrimidin-5(10H)-one
InChi Key: RSAQARAFWMUYLL-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-22-11-13-26(15-19-8-3-2-4-9-19)17-21(22)23(29)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3
SMILES Code: O=C1C(CN(CC2=CC=CC=C2)CC3)=C3N(CC4=CC=CC=C4C)C5=NCCN15
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
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).
HS Tariff Code: 2934.99.9001
|Biological target:||TIC10 isomer does not possess the reported biological activity of inducing TRIAL expression.|
|In vitro activity:||TBD|
|In vivo activity:||TBD|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 386.48944 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||TBD|
|In vivo protocol:||TBD|
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.
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.