Molibresib

Molibresib (I-BET762; GSK525762) is a BET bromodomain inhibitor with IC₅₀ of 32.5-42.5 nM. IC50 & Target:IC50: 32.5-42.5 nM (BET)^[1] In Vitro:Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant K_d of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC₅₀ of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET^[1]. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin^[2]. Molibresib inhibits OPM-2 cell proliferation with IC₅₀ of 60.15 nM^[3]. In Vivo:The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an in vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib^[3].