WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206932
Description: ONC206 is a chemical analogue of ONC201. ONC206 is a benzyl-flurobenzyl imipridone that has highly potent activity in preclinical models of difficult-to-treat neuroendocrine tumors and sarcomas. ONC206 acts as a selective antagonist of DRD2 at nanomolar concentrations and has broad-spectrum anti-tumor activity. ONC206 may address tumor types where the properties of ONC201 do not permit for complete therapeutic engagement in vivo.
MedKoo Cat#: 206932
Chemical Formula: C23H22F2N4O
Exact Mass: 408.176
Molecular Weight: 408.4528
Elemental Analysis: C, 67.63; H, 5.43; F, 9.30; N, 13.72; O, 3.92
Synonym: ONC206; ONC-206; ONC 206.
IUPAC/Chemical Name: 7-benzyl-4-(2,4-difluorobenzyl)-2,4,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one
InChi Key: ITMGVSSHWMTJRR-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H22F2N4O/c24-18-7-6-17(20(25)12-18)14-29-22(30)19-15-27(13-16-4-2-1-3-5-16)10-8-21(19)28-11-9-26-23(28)29/h1-7,12H,8-11,13-15H2
SMILES Code: FC1=CC(F)=CC=C1CN2C(C(C3)=C(N4CCN=C42)CCN3CC5=CC=CC=C5)=O
In vitro efficacy profiling of ONC206 in the Genomic of Drug Sensitivity in Cancer collection of cell lines revealed broad efficacy across most tumor types (GI50 <78-889nM). Bone cancer and neuroblastoma were identified as the most ONC206-responsive solid tumor types that were comparatively less responsive to ONC201. Within bone cancer cell lines, Ewing’s sarcoma (n=16) was the most sensitive to ONC206 with nanomolar sensitivity (GI50 168-303nM) that was superior to ONC201. ONC206 was highly efficacious in neuroblastoma (n=35, GI50 87-589nM) including cell lines derived from metastatic sites and with MYCN amplification associated with poor prognosis. In the PC12 rat pheochromocytoma cell line ONC206 (GI50 200nM) was superior to ONC201. ONC206 time-course experiments revealed anti-cancer effects occurring at 48-72 post-treatment, similar to ONC201. In support of a wide therapeutic window, ONC206 reduced the viability of normal fibroblasts (HFF-1) at relatively high doses (GI50 > 5µM). Efficacy evaluations in MHH-ES-1 athymic nude mice xenografts demonstrated that ONC206 (100 mg/kg PO every 10 days) causes significant tumor growth inhibition that was comparable to methotrexate (400 mg/kg, IP) while being better tolerated. (http://cancerres.aacrjournals.org/content/77/13_Supplement/4147A)
1: Ishida CT, Zhang Y, Bianchetti E, Shu C, Nguyen TTT, Kleiner G, Sanchez-Quintero MJ, Quinzii CM, Westhoff MA, Karpel-Massler G, Prabhu VV, Allen JE, Siegelin MD. Metabolic Reprogramming by Dual AKT/ERK Inhibition through Imipridones Elicits Unique Vulnerabilities in Glioblastoma. Clin Cancer Res. 2018 Nov 1;24(21):5392-5406. doi: 10.1158/1078-0432.CCR-18-1040. Epub 2018 Jul 23. PubMed PMID: 30037819; PubMed Central PMCID: PMC6214769.
2: Wagner J, Kline CL, Ralff MD, Lev A, Lulla A, Zhou L, Olson GL, Nallaganchu BR, Benes CH, Allen JE, Prabhu VV, Stogniew M, Oster W, El-Deiry WS. Preclinical evaluation of the imipridone family, analogs of clinical stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212. Cell Cycle. 2017 Oct 2;16(19):1790-1799. doi: 10.1080/15384101.2017.1325046. Epub 2017 May 10. PubMed PMID: 28489985; PubMed Central PMCID: PMC5628644.