Biological Activity
GSK 525762A is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.
In Vitro
GSK 525762A (I-BET 762) shows the highest affinity interaction with BET. GSK 525762A binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). GSK 525762A 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]. GSK 525762A has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. GSK 525762A treatment leads to a reduction in the recruitment of all three proteins to chromatin[2]. GSK 525762A inhibits OPM-2 cell proliferation with IC50 of 60.15 nM[3].
In Vivo
The antimyeloma activity of GSK 525762A (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 GSK 525762A 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 GSK 525762A[3].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.