PROTAC BRD3/BRD4-L degrader-2, a PROTAC molecule, selectively degrades cellular BRD3 and BRD4-L with K i values of 16.91 and 2.8 nM, respectively, and exhibits robust antitumor activity in mouse xenograft models, serving as a research tool for cancer [1].

PROTAC BRD3/BRD4-L degrader-2 (Compound 28) exhibits binding affinity to BRD3 BD1 and BRD3 BD2 with K_i values of 16.91 nM and 2.8 nM, respectively [1]. It shows cellular activity in MV4-11 and MM.1S cell lines with IC50 values of 7.46 nM and 85.4 nM [1], and selectively degrades BRD3 and BRD4-L in a time-dependent manner at 30 nM over 1, 3, 6, 8, and 24 hours [1]. At concentrations of 1, 3, 10, 30, 100, and 300 nM for 24 hours, it demonstrates antitumor activity in MM.1S cells and induces G1 phase cell cycle arrest in a dose-dependent manner [1].

PROTAC BRD3/BRD4-L degrader-2 (compound 28) demonstrates poor oral bioavailability, yet exhibits good systemic exposure when administered intravenously (i.v.; 3 mg/kg) [1]. When given intravenously (i.v.; 3 mg/kg), PROTAC BRD3/BRD4-L degrader-2 shows antitumor efficacy in the MM.1S mouse xenograft model [1]. Furthermore, single doses administered intravenously (i.v.; 1, 5 mg/kg) promote selective degradation of BRD3 and BRD4-L and exhibit potent antitumor activity [1].