ONC206

ONC206 is an analogue of TRAIL inducer ONC201[1]. ONC206 is a selective antagonist of the D2-like dopamine receptors (DRD2/3/4) at nanomolar concentrations. ONC206 has broad-spectrum anti-tumor activity[2].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

DRD2/3/4[2]

ONC206 selectively antagonizes the D2-like (DRD2/3/4), but not the D1-like (DRD 1/5), subfamily of dopamine receptors[2]. ONC206 significantly inhibits tumor cell migration and invasion in vitro[1]. ONC206 (0.05 μM; Over 48 hours) inhibits migration of ONC201- and TRAIL-resistant HCT116 Bax−/− cells without inducing cell death or inhibiting cell proliferation[1]. ONC206 engages the ISR and TRAIL pathway leading to tumor growth arrest and cell death[1]. ONC206 does not induce cell cycle arrest in a colorectal cell line with acquired ONC201-resistance[1]. Cell Proliferation Assay[1] Cell Line: HCT116 cells Concentration: 0.05 μM Incubation Time: Over 48 hours Result: Inhibited migration of ONC201- and TRAIL-resistant HCT116 Bax−/− cells.

ONC206 (100 mg/kg;p.o.; every 10 days) causes significant tumor growth inhibition[2].

[1]. Wagner J, et al. 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.

[2]. Varun Vijay Prabhu, et al. Potent anti-cancer activity of the imipridone ONC206: A selective dopamine D2-like receptor antagonist. AACR Annual Meeting 2017, April 1-5, 2017; Washington, DC.