brd3

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].

BETd-260, a PROTAC linked by a Cereblon ligand and a BET ligand, has an inhibitory effect on BRD4 protein in leukemic cell lines.

ARV-771 is an effective BET degrader based on PROTAC technology. The Kd for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1) and BRD4(2) are 34 and 4.7 respectively. , 8.3, 7.6, 9.6 and 7.6 nM.

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).

PROTAC BRD4 Degrader-27 is a selective PROTAC targeting BRD4, distinguished from BRD2 BRD3. This compound is composed of the E3 ubiquitinase ligand Thalidomide-4-OH, the PROTAC Linker γ-Aminobutyric acid, and the PROTAC target protein ligand PROTAC BRD4 ligand-3. The active control for this target protein ligand is Mivebresib, while the conjugate of the E3 ubiquitin ligase ligand and Linker is identified as Pomalidomide 4'-alkylC3-acid.

Me-SJ46411 is an E3 ubiquitin ligase ligand used in the synthesis of PROTAC molecules. For instance, when combined with the PROTAC linker Boc-Piperazine-OH and the target protein ligand (+)-JQ-1, Me-SJ46411 can be employed to create the selective BRD3 PROTAC degrader SJ46420.

MZ 1 is a BRD4 protein degrader based on PROTAC technology.

KB02-JQ1 is a potent and specific proteolysis targeting chimera (PROTAC) that specifically degrades BRD4, acting as a molecular glue. It does not degrade BRD2 or BRD3. The mechanism of action involves covalent modification of the E3 ligase DCAF16, thereby promoting BRD4 degradation. Importantly, KB02-JQ1 demonstrates enhanced stability and durability in facilitating protein degradation within biological systems. The compound forms a complex with the ubiquitin E3 ligase ligand KB02 through a linker, resulting in the formation of KB02-JQ1[1].

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].

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

SJ44236 is a BET PROTAC degrader capable of degrading BRD2 (DC50 = 0.127 nM), BRD3, and BRD4. It shows cytotoxicity in MV4-11 and HD-MB03 cells with IC50 values of 0.12 nM and 0.92 nM, respectively. The compound downregulates c-Myc expression and upregulates p53 expression. In mice, SJ44236 demonstrates good oral bioavailability (45%). [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonE3ligaseLigand 54]

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

PROTAC BRD2 BRD4 degrader-1 (compound 15) is a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination compared to BRD3. It effectively suppresses solid tumors with minimal cytotoxic effects and comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN) cullin 4A[1].

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

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.

OARV-771, a VHL-based BET degrader (PROTAC) featuring enhanced cell permeability, demonstrates DC50 values of 6 nM for Brd4, 1 nM for Brd2, and 4 nM for Brd3, respectively [1].

SIM1 is a potent and selective trivalent PROTAC®Degrader based on BET bromodomain inhibitors linked to a Von Hippel Lindau (VHL) ligand via branched linkers. SIM1 degrades all BET family proteins with a preference for BRD2 (DC50values = 0.7 nM, 1.1 nM and 3.3 nM for BRD4, BRD2 and BRD3, respectively). SIM1 degrades BRD2 more significantly and rapidly than BRD3 and BRD4, and degrades BET proteins with a higher potency than a bivalent degrader. SIM1 also decreases protein levels for Myc and HMOX1 and induces apoptosis in prostate cancer cells.

AB3067 is a PROTAC degrader targeting BET protein, efficiently recruiting two distinct E3 ligases, Cereblon and VHL, with strong affinity (demonstrated by IC50 values of 559 nM for VHL and 190 nM for CRBN in vivo HEK293). It degrades BRD2, BRD3, BRD4, and CRBN with DC50 values of 2.1~2.3, 1.6, 15, and 75 nM, respectively. Additionally, AB3067 inhibits the proliferation of RKO cells, with an EC50 of 111 nM. (Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase VHL and CRBN)

SJ46420, a potent and selective precursor variant of SJ46421, functions as a BRD3 PROTAC degrader through a KLHDC2-dependent mechanism. This compound specifically degrades BRD3, which concurrently results in the partial reduction of BRD2 or BRD4 levels.