brd4 (bd2)

MZP-54 is a selective degrader of BRD3/4 based on PROTAC technology(Kd of 4 nM for Brd4BD2)

MZP-55 is a selective BRD3/4 degrader based on PROTAC technology(Brd4BD2 with Kd of 8 nM)

GNE-987 is a highly active chimeric BET degrader. GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50: 4.7 and 4.4 nM, respectively). GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50: 0.03

(S)-GNE-987 binds to the BRD4 BD1(IC50=4 nM) and BD2 (3.9 nM) bromodomains and can be used to design PROTAC-Antibody Conjugate (PAC).

ZEN-3862 (Willardiine) is an inhibitor of BET(IC50s of 0.16 and 0.13 μM for BRD4(BD1) and BRD4(BD2) , respectively). ZEN-3862 can be used to form PROTACs to induce degradation of BRD4.

HJB97 is used for the design of potential PROTAC BET degrader. It also has antitumor activity. HJB97 is a high-affinity inhibitor of BET (Kis: 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), 1.0 nM (BRD4 BD2), respectively).

SJ46421, a PROTAC protein degrader derived from (+)-JQ-1, targets KLHDC2. It efficiently forms a stable ternary complex with KLHDC2, exhibiting an IC50 of 7.8 nM. Furthermore, SJ46421 promotes the polyubiquitination of the BD2 domain of BRD2, BRD3, or BRD4.

PROTAC BRD4 Degrader-15 is a chemical compound consisting of a PROteolysis TArgeting Chimera (PROTAC) linked to ligands specific to von Hippel-Lindau and BRD4. It exhibits an IC50 of 7.2 nM for BRD4 BD1 and 8.1 nM for BRD4 BD2 and demonstrates potent degradation activity against the BRD4 protein in PC3 prostate cancer cells.

ARV-825, a heterobifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested.

BRD4 degrader AT1 is a highly selective Brd4 degrader based on PROTAC technology, with a Kd of 44 nM for Brd4BD2 in cells.

MS479 is a BRD4 PROTAC degrader that binds with high affinity to BRD4-BD2 and GLP (BRD4-BD2: Kd = 200 nM; GLP: Kd = 306 nM). It effectively reduces the protein levels of BRD4 short isoforms. By directly binding to its substrate GLP, MS479 recruits the E3 ligase SPOP as a bridging protein. Additionally, MS479 can be utilized to inhibit the proliferation of colorectal cancer cells.

PROTACBRD4 Degrader-34 is a selective BRD4 PROTAC degrader (pDC50= 8.4) that induces VHL-mediated BD2 degradation and is applicable for cancer research.

PROTAC BRD4 Degrader-8 is a potent BRD4 inhibitor with IC50 values of 1.1 nM and 1.4 nM for BRD4 BD1 and BD2, respectively, effectively degrading the BRD4 protein in PC3 prostate cancer cells[1].

PROTAC BRD4 Degrader-7, a potent bromodomain BRD4 inhibitor exemplified by compound 1a, demonstrates half-maximal inhibitory concentrations (IC50s) of 15.5 nM and 12.3 nM for BRD4-BD1 and BRD4-BD2, respectively [1].

PROTAC BRD4 Degrader-14, a PROTAC (Proteolysis Targeting Chimera) linked by ligands to von Hippel-Lindau and BRD4, exhibits IC50 values of 1.8 nM and 1.7 nM for BRD4 BD1 and BD2, respectively. This compound effectively degrades the BRD4 protein in PC3 prostate cancer cells [1].

TMX1 is a molecular glue degrader targeting BRD4, selectively recruiting the ubiquitin ligase CUL4-DCAF16 complex to BRD4 (BD2), leading to subsequent degradation via covalent modification.

GXF-111, a proteolysis targeting chimera (PROTAC) molecule, efficiently induces the selective degradation of the BRD3 and BRD4-L proteins. It exhibits high binding affinities to both BRD3 BD1 and BRD3 BD2, with K i values of 11.97 nM and 2.35 nM, respectively. This compound is utilized in cancer research [1].