protac brd2/brd4 degrader-1

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].

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.

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.

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]

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].