ONC201 HCl
ONC-201, also known as TIC10 and imipridone, 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.
For research use only. We do not sell to patients.
Chemical Information
| Name | ONC201 HCl |
|---|---|
| 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 dihydrochloride |
| Synonyms | ONC-201 Dihydrochloride ;ONC-201 HCl ; ONC201 ; ONC 201 ; ONC-201 ; NSC350625 ; NSC-350625 ; NSC 350625 ; imipridone; TIC10 ; TIC 10 ; TIC-10 ; |
| Molecular Formula | C24H28Cl2N4O |
| Molecular Weight | 459.41 |
| Smile | O=C1N(CC2=CC=CC=C2C)C3=NCCN3C4=C1CN(CC5=CC=CC=C5)CC4.[H]Cl.[H]Cl |
| InChiKey | HKBXPCQCBQFDML-UHFFFAOYSA-N |
| InChi | InChI=1S/C24H26N4O.2ClH/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;2*1H |
| CAS Number | 1638178-82-1 |
| Related CAS | 41276-02-2 (TIC10 isomer) 1616632-77-9 (free base) 1638178-82-1 (HCl) 1777785-71-3 (HBr) 2007141-57-1 (2HBr) |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | 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 |
| Handling | |
| 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. |
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| Mechanism | |
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| Clinical study |
1: Pruss M, Dwucet A, Tanriover M, Hlavac M, Kast RE, Debatin KM, Wirtz CR, Halatsch ME, Siegelin MD, Westhoff MA, Karpel-Massler G. Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma. Br J Cancer. 2020 Apr;122(8):1146-1157. doi: 10.1038/s41416-020-0759-0. Epub 2020 Mar 2. PMID: 32115576; PMCID: PMC7156767.
2: Jacques S, van der Sloot AM, C Huard C, Coulombe-Huntington J, Tsao S, Tollis S, Bertomeu T, Culp EJ, Pallant D, Cook MA, Bonneil E, Thibault P, Wright GD, Tyers M. Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development. Genetics. 2020 Apr;214(4):1103-1120. doi: 10.1534/genetics.119.302851. Epub 2020 Feb 24. PMID: 32094149; PMCID: PMC7153937.
3: Dianat-Moghadam H, Heidarifard M, Mahari A, Shahgolzari M, Keshavarz M, Nouri M, Amoozgar Z. TRAIL in oncology: From recombinant TRAIL to nano- and self- targeted TRAIL-based therapies. Pharmacol Res. 2020 May;155:104716. doi: 10.1016/j.phrs.2020.104716. Epub 2020 Feb 18. PMID: 32084560.
4: Wierzbicki K, Ravi K, Franson A, Bruzek A, Cantor E, Harris M, Homan MJ, Marini BL, Kawakibi AR, Ravindran R, Teodoro R, Yadav VN, Koschmann C. Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma. Curr Oncol Rep. 2020 Feb 6;22(2):19. doi: 10.1007/s11912-020-0877-0. Erratum in: Curr Oncol Rep. 2020 Apr 16;22(5):47. PMID: 32030483.
5: Madhukar NS, Khade PK, Huang L, Gayvert K, Galletti G, Stogniew M, Allen JE, Giannakakou P, Elemento O. A Bayesian machine learning approach for drug target identification using diverse data types. Nat Commun. 2019 Nov 19;10(1):5221. doi: 10.1038/s41467-019-12928-6. PMID: 31745082; PMCID: PMC6863850.
6: Arrillaga-Romany I, Odia Y, Prabhu VV, Tarapore RS, Merdinger K, Stogniew M, Oster W, Allen JE, Mehta M, Batchelor TT, Wen PY. Biological activity of weekly ONC201 in adult recurrent glioblastoma patients. Neuro Oncol. 2020 Jan 11;22(1):94-102. doi: 10.1093/neuonc/noz164. PMID: 31702782; PMCID: PMC7080220.
7: Chi AS, Tarapore RS, Hall MD, Shonka N, Gardner S, Umemura Y, Sumrall A, Khatib Z, Mueller S, Kline C, Zaky W, Khatua S, Weathers SP, Odia Y, Niazi TN, Daghistani D, Cherrick I, Korones D, Karajannis MA, Kong XT, Minturn J, Waanders A, Arillaga-Romany I, Batchelor T, Wen PY, Merdinger K, Schalop L, Stogniew M, Allen JE, Oster W, Mehta MP. Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201. J Neurooncol. 2019 Oct;145(1):97-105. doi: 10.1007/s11060-019-03271-3. Epub 2019 Aug 27. PMID: 31456142.
8: Zhao R, Li Y, Gorantla S, Poluektova LY, Lin H, Gao F, Wang H, Zhao J, Zheng JC, Huang Y. Small molecule ONC201 inhibits HIV-1 replication in macrophages via FOXO3a and TRAIL. Antiviral Res. 2019 Aug;168:134-145. doi: 10.1016/j.antiviral.2019.05.015. Epub 2019 May 31. PMID: 31158413; PMCID: PMC6620139.
9: Cao Z, Liao Q, Su M, Huang K, Jin J, Cao D. AKT and ERK dual inhibitors: The way forward? Cancer Lett. 2019 Sep 10;459:30-40. doi: 10.1016/j.canlet.2019.05.025. Epub 2019 May 23. PMID: 31128213.
10: Nii T, Prabhu VV, Ruvolo V, Madhukar N, Zhao R, Mu H, Heese L, Nishida Y, Kojima K, Garnett MJ, McDermott U, Benes CH, Charter N, Deacon S, Elemento O, Allen JE, Oster W, Stogniew M, Ishizawa J, Andreeff M. Imipridone ONC212 activates orphan G protein-coupled receptor GPR132 and integrated stress response in acute myeloid leukemia. Leukemia. 2019 Dec;33(12):2805-2816. doi: 10.1038/s41375-019-0491-z. Epub 2019 May 24. PMID: 31127149; PMCID: PMC6874902.
11: Stein MN, Malhotra J, Tarapore RS, Malhotra U, Silk AW, Chan N, Rodriguez L, Aisner J, Aiken RD, Mayer T, Haffty BG, Newman JH, Aspromonte SM, Bommareddy PK, Estupinian R, Chesson CB, Sadimin ET, Li S, Medina DJ, Saunders T, Frankel M, Kareddula A, Damare S, Wesolowsky E, Gabel C, El-Deiry WS, Prabhu VV, Allen JE, Stogniew M, Oster W, Bertino JR, Libutti SK, Mehnert JM, Zloza A. Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer. 2019 May 22;7(1):136. doi: 10.1186/s40425-019-0599-8. PMID: 31118108; PMCID: PMC6532211.
12: Wang S, Dougan DA. The Direct Molecular Target for Imipridone ONC201 Is Finally Established. Cancer Cell. 2019 May 13;35(5):707-708. doi: 10.1016/j.ccell.2019.04.010. PMID: 31085171.
13: Ishizawa J, Zarabi SF, Davis RE, Halgas O, Nii T, Jitkova Y, Zhao R, St- Germain J, Heese LE, Egan G, Ruvolo VR, Barghout SH, Nishida Y, Hurren R, Ma W, Gronda M, Link T, Wong K, Mabanglo M, Kojima K, Borthakur G, MacLean N, Ma MCJ, Leber AB, Minden MD, Houry W, Kantarjian H, Stogniew M, Raught B, Pai EF, Schimmer AD, Andreeff M. Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality. Cancer Cell. 2019 May 13;35(5):721-737.e9. doi: 10.1016/j.ccell.2019.03.014. Epub 2019 May 2. PMID: 31056398; PMCID: PMC6620028.
14: Graves PR, Aponte-Collazo LJ, Fennell EMJ, Graves AC, Hale AE, Dicheva N, Herring LE, Gilbert TSK, East MP, McDonald IM, Lockett MR, Ashamalla H, Moorman NJ, Karanewsky DS, Iwanowicz EJ, Holmuhamedov E, Graves LM. Mitochondrial Protease ClpP is a Target for the Anticancer Compounds ONC201 and Related Analogues. ACS Chem Biol. 2019 May 17;14(5):1020-1029. doi: 10.1021/acschembio.9b00222. Epub 2019 May 1. PMID: 31021596; PMCID: PMC6528275.
15: Hall MD, Odia Y, Allen JE, Tarapore R, Khatib Z, Niazi TN, Daghistani D, Schalop L, Chi AS, Oster W, Mehta MP. First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M-mutant pediatric diffuse intrinsic pontine glioma: a case report. J Neurosurg Pediatr. 2019 Apr 5:1-7. doi: 10.3171/2019.2.PEDS18480. Epub ahead of print. PMID: 30952114.
16: Ma Z, Gao G, Fang K, Sun H. Development of Novel Anticancer Agents with a Scaffold of Tetrahydropyrido[4,3-d]pyrimidine-2,4-dione. ACS Med Chem Lett. 2019 Jan 16;10(2):191-195. doi: 10.1021/acsmedchemlett.8b00531. PMID: 30783502; PMCID: PMC6378674.
17: Prabhu VV, Madhukar NS, Gilvary C, Kline CLB, Oster S, El-Deiry WS, Elemento O, Doherty F, VanEngelenburg A, Durrant J, Tarapore RS, Deacon S, Charter N, Jung J, Park DM, Gilbert MR, Rusert J, Wechsler-Reya R, Arrillaga-Romany I, Batchelor TT, Wen PY, Oster W, Allen JE. Dopamine Receptor D5 is a Modulator of Tumor Response to Dopamine Receptor D2 Antagonism. Clin Cancer Res. 2019 Apr 1;25(7):2305-2313. doi: 10.1158/1078-0432.CCR-18-2572. Epub 2018 Dec 17. PMID: 30559168.
18: Fang Z, Wang J, Clark LH, Sun W, Yin Y, Kong W, Pierce SR, West L, Sullivan SA, Tran AQ, Prabhu VV, Zhou C, Bae-Jump V. ONC201 demonstrates anti-tumorigenic and anti-metastatic activity in uterine serous carcinoma in vitro. Am J Cancer Res. 2018 Aug 1;8(8):1551-1563. PMID: 30210923; PMCID: PMC6129479.
19: Bárány P, Oláh RS, Kovács I, Czuczi T, Szabó CL, Takács A, Lajkó E, Láng O, Kőhidai L, Schlosser G, Bősze S, Mező G, Hudecz F, Csámpai A. Ferrocene- Containing Impiridone (ONC201) Hybrids: Synthesis, DFT Modelling, In Vitro Evaluation, and Structure⁻Activity Relationships. Molecules. 2018 Sep 3;23(9):2248. doi: 10.3390/molecules23092248. PMID: 30177664; PMCID: PMC6225426.
20: Ralff MD, Lulla AR, Wagner J, El-Deiry WS. ONC201: a new treatment option being tested clinically for recurrent glioblastoma. Transl Cancer Res. 2017 Oct;6(Suppl 7):S1239-S1243. doi: 10.21037/tcr.2017.10.03. PMID: 30175049; PMCID: PMC6117120.
Chemical Structure
