protac brd4 degrader 1

PROTAC BRD4 Degrader-1 is an efficacious degrader of BRD4(BRD4 BD1,IC50 of 41.8 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].

PROTAC BRD4 degrader for PAC-1 (compound 5) is a chimeric BET degrader GNE-987 conjugated with a disulfide-containing linker[1]. This PROTAC-linker conjugate specifically targets and degrades BRD4, enabling selective proteolysis of PAC-1.

PROTACBRD4-DCAF1 degrader-1 (I-907) is a PROTAC degrader targeting BRD4-DCAF1, exhibiting a DC50 range of 10~100 nM.

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.

BET-IN-6, a ligand with potent and high affinity for inhibiting BRD2 BRD4, plays a crucial role in the synthesis of PROTAC BRD2 BRD4 degrader-1 [1], targeting the protein BRD2 4.

PROTAC BRD9 Degrader-1 is a leading PROTAC BRD9 chemical degrader with an IC50 of 13.5 nM.

Azido-PEG1-CH2CO2H, a PROTAC linker characterized by an alkyl ether combination, can be utilized to synthesize PROTAC BRD4 Degrader-1[1].

Azido-PEG1-CH2COO-Cl (compound 43a) is an alkyl ether-based PROTAC linker commonly used in the synthesis of PROTAC BRD4 Degrader-1[1].

Lenalidomide-PEG1-azide is an E3 ligase ligand-linker conjugate that incorporates the cereblon ligand based on Lenalidomide and a linker. It is designed for use in the development of PROTAC BRD4 Degrader-2[1].

Pomalidomide-PEG1-azide is an E3 ligase ligand-linker conjugate that combines the cereblon ligand based on Pomalidomide with a linker. This compound is instrumental in designing PROTAC BRD4 Degrader-1[1].

Thalidomide-NH-C4-NH2 TFA (compound 29c) is a conjugate composed of an E3 ligase ligand-linker that integrates a Thalidomide-based cereblon ligand and a linker moiety. This compound is used as a component in PROTAC BRD2 BRD4 degrader-1, a highly potent and selective degrader targeting BET proteins BRD4 and BRD2[1].

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.

JQ-1 (carboxylic acid)-NH-C2-NH-AMPRO-222 incorporates a BRD4 ligand and a PROTAC linker, and is used in the synthesis of PROTAC BRD4 Degrader-29.

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]

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].

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

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-11 (compound 9a), a PROTAC linked through ligands to von Hippel-Lindau and BRD4, effectively targets and degrades the BRD4 protein in PC3 prostate cancer cells when conjugated with STEAP1 and CLL1 antibodies, exhibiting potent activity with DC50 values of 0.23 nM and 0.38 nM for the respective conjugations [1].

PROTAC BRD4 Degrader-12 (compound 9c) is a PROTAC that links von Hippel-Lindau and BRD4 ligands. When conjugated with STEAP1 and CLL1 antibodies, this compound effectively degrades BRD4 protein in PC3 prostate cancer cells, demonstrating potent activity with DC50 values of 0.39 nM and 0.24 nM, 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].

PROTAC BRD4 Degrader-17 (compound 13i), a potent inhibitor, exhibits IC50 values of 29.54 nM (BRD4 (BD1)) and 3.82 nM (BRD4 (BD2)), effectively reducing Cyclin B1 expression linked with G2 M phase progression and significantly inducing apoptosis in MV-4-11 cells [1].

XY-06-007, a potent and selective bump-and-hole (B&H) PROTAC BRD4 BD1 L94V degrader, exhibits a DC50, 6 h of 10 nM specifically against BRD4 BD1 L94V without degrading off-targets. It also demonstrates favorable pharmacokinetics for in vivo studies [1].

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].