Biological Activity of (+)-JQ-1

(+)-JQ1 is a BET bromodomain inhibitor, with IC50 of 77 nM/33 nM for BRD4(1/2).
IC50 Value: 77 nM(for BRD4(1)); 33 nM( for BRD4(2))
Target: BRD4
in vitro: (+)-JQ1 enantiomer binds directly into the Kac binding site of BET bromodomains. (+)-JQ1 (500 nM) binds BRD4 competitively with chromatin resulting in differentiation and growth arrest of NMC cells. (+)-JQ1 (500 nM) attenuates rapid proliferation of NMC 797 and Per403 cell lines as demonstrated by reduced Ki67 staining. (+)-JQ1 (500 nM) potently decreases expression of both BRD4 target genes in NMC 797 cells. (+)-JQ1 inhibits cellular viability with IC50 of 4 nM in NMC 11060 cells. (+)-JQ1 results in robust inhibition of MYC expression in MM cell lines. (+)-JQ1 inhibits proliferating of KMS-34 and LR5 with IC50 of 68 nM and 98 nM, respectively. (+)-JQ1 (500 nM)-treated MM.1S cells results in a pronounced decrease in the proportion of cells in S-phase, with a concomitant increase in cells arrested in G0/G1. (+)-JQ1 (500 nM) results in pronounced cellular senescence by beta-galactosidase staining. (+)-JQ1 (800 nM) exposure leads to a significant reduction in cell viability among the majority of CD138+ patient-derived MM samples tested. (+)-JQ1 inhibits growth of LP-1 cells with GI50 of 98 nM. (+)-JQ1 (625 nM) results in an increase in the percentage of LP-1 cells in G0/G1. (+)-JQ1 (500 nM) suppresses the expression of MYC, BRD4 and CDK9 in LP-1 cells.
in vivo: (+)-JQ1 (50 mg/kg) inhibits tumors growth in mice with NMC 797 xenografts. (+)-JQ1 (50 mg/kg) results in effacement of NUT nuclear speckles in mice with NMC 797 xenografts, consistent with competitive binding to nuclear chromatin. (+)-JQ1 (50 mg/kg) induces strong (grade 31) keratin expression in NMC 797 xenografts. (+)-JQ1 (50 mg/kg) promotes differentiation, tumor regression and prolonged survival in mice models of NMC xenografts. (+)-JQ1 (50 mg/kg) results in a significant prolongation in overall survival of SCID-beige mice orthotopically xenografted after intravenous injection with MM.1S-luc+ cells compared to vehicle-treated animals. (+)-JQ1 (50 mg/kg i.p.) leads to a highly significant increase in survival of mice bearing Raji xenografts.