GNE-064

GNE-064 (compound 5) is a selective, orally active and highly soluble inhibitor of SMARCA4, SMARCA2 and PBRM1 bromodomains 5. GNE-064 inhibits SMARCA4 with an IC50 of 0.035 μM and inhibits SMARCA2 with an EC50 of 0.10 μM. GNE-064 possess Kds with 0.01, 0.016, 0.018 and 0.049 μM for SMARCA4, SMARCA2, PBRM1 bromodomains 5 and PBRM1 bromodomains 2, repectively. GNE-064 can be used as a chemical probe for the research of drug synthesis[1].

Research Areas >> Others

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

IC50: 0.035 μM (SMARCA4)[1]

GNE-064 (0-0.5 μM; 1 h) inhibits SMARCA2 in ZsGreen-SMARCA2 BD-expressing U2OS cells[1]. Cell Viability Assay[1] Cell Line: ZsGreen-SMARCA2 BD-expressing U2OS cells Concentration: 0-0.5 μM Incubation Time: 1 hour Result: Inhibited SMARCA2 in ZsGreen-SMARCA2 BD-expressing U2OS cells with an EC50 of 0.1 μM.

GNE-064 (compound 5) (0.5 and 1.0 mg/kg; i.v. and p.o. once ) exibits ideal pharmacokinetics value in female CD-1 mice [1]. Animal Model: Female CD-1 mice[1] Dosage: 0.5 mg/kg (i.v.) and 1.0 mg/kg (p.o.) Administration: Intravenous injection and oral gavage; 0.5 mg/kg and 1.0 mg/kg once Result: Showed a low unbound plasma clearance with 16 mL/min/kg, a reasonable half-life of 1.1 h and good oral bioavailability of 59%.

[1]. Taylor AM, et al. GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1. J Med Chem. 2022 Aug 5.