BRD4 Degrader

ARV-771 is a potent BET PROTAC based on E3 ligase von Hippel-Lindau with K_ds of 34 nM, 4.7 nM, 8.3 nM, 7.6 nM, 9.6 nM, and 7.6 nM for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1), and BRD4(2), respectively.

PROTAC BRD4 Degrader-45 is a PROTAC degrader targeting BRD4, with a DC₅₀ of 43 nM. PROTAC BRD4 Degrader-45 is applicable to studies on membrane-permeable PROTACs.

SIM1 is a potent von Hippel-Lindau (VHL)-based trivalent PROTAC capable of degradation for all BET family members, with preference for BRD2 degradation (IC₅₀=1.1 nM; Kd=186 nM). SIM1 shows sustained anti-cancer activity.

TMX1 is a covalent, selective BRD4 molecular glue degrader. TMX1 binds to the JQ1-binding site of BRD4BD2, forms covalent bonds with Cys58 of DCAF16 and Cys87 of GAK in a BRD4BD2-dependent template-assisted manner, stabilizes the BRD4-TMX1-DCAF16 ternary complex, and promotes the ubiquitination of BRD4 via the CRL4_DCAF16 ubiquitin ligase complex. TMX1 induces selective degradation of BRD4, mild degradation of BRD2 and BRD3, as well as DCAF16-dependent cytotoxicity.

IBG1 is a molecular glue degrader targeting BRD2 and BRD4 (DC₅₀: 0.15 nM). IBG1 has no significant degradation effect on its paralogue BRD3. IBG1 can inhibit the growth of cancer cells and can be used in tumor research. (Pink: BRD2/BRD4 Ligand (HY-111139); Black: Linker; Blue: DCAF15 ligand-1 (HY-W037495)).

MMH2 is a novel BRD4 molecular glue degrader that functions by recruiting the CUL4 and DCAF16 ligases to the second bromodomain of BRD4 (BRD4_BD2).

BRD4 degrader-1 (Compound mL 1-50) is a relatively selective, monovalent and covalent BRD4 Molecular glue degrader. BRD4 degrader-1 induces degradation of both long and short isoforms of BRD4 by targeting DCAF16 (an E3 ligase). BRD4 degrader-1 can be used in breast cancer research.

BRD4 degrader-3 is a potent bromodomain BRD4 degrader extracted from patent WO2020055976A1, example 1a, has IC₅₀s of 15.5 and 12.3 nM for BRD4-BD1 and BRD4-BD2, respectively. PROTAC BRD4 Degrader-7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

MMH1 is a novel BRD4 molecular glue degrader that functions by recruiting the CUL4 and DCAF16 ligases to the second bromodomain of BRD4 (BRD4_BD2).

PROTAC BET Degrader-12 (Compound 8b) is a PROTAC degrader for bromodomain and extra-terminal domain (BET)-containing proteins, which degrades the BRD3 and BRD4 in a DCAF11-dependent manner. PROTAC BET Degrader-12 inhibits cell viability of KBM7 with a DC₅₀ of 305.2 nM

BD-9136 is a selective BRD4 PROTAC degrader with a DC₅₀ of 1.2 nM, and exhibits a selectivity of ≥1000-fold over BRD2 and BRD3. BD-9136 preferentially forms a ternary complex with the BD1 domain of BRD4, and downregulates the expression of B7-H4 by disrupting the PR-P300-BRD4 axis. BD-9136 depletes BRD4 protein in tumor tissues, inhibits tumor growth, reduces B7-H4 protein expression, increases CD8+ T cell infiltration, and enhances tumor sensitivity to anti-PD-L1. Degradation of BRD4 by BD-9136 rescues the erythroid differentiation block induced by LSD1 inhibition, and transient administration restores erythroid output while retaining HbF induction. BD-9136 causes no adverse effects in mice at effective doses. BD-9136 can be used in studies related to acute myeloid leukemia, acute lymphoblastic leukemia and breast cancer.

JQ-1-Azidopropylamine is an Target Protein Ligand-Linker Conjugate that incorporates a ligand for BRD4 (HY-78695) and a PROTAC linker (HY-151862), which recruits E3 ligases. JQ-1-Azidopropylamine can be used for synthesis of PROTAC JY-21 (HY-174975).

SJ995973 is a BRD4 PROTAC degrader with DC₅₀ values of 0.87 nM (12 h) and 0.16 nM (24 h), respectively. SJ995973 induces the formation of a ternary complex between purified BRD4 and CRBN-DDB1 proteins, with an IC₅₀ of 17 nM against CRBN. SJ995973 inhibits the viability of human acute myeloid leukemia cells. SJ995973 can be used in studies related to acute myeloid leukemia and medulloblastoma.

β-NF-JQ1 is a BRD2/3/4 PROTAC degrader. β-NF-JQ1 recruits the AhR E3 ligase complex to BRD2, BRD3 and BRD4, induces AhR-BRD interaction, and mediates AhR-dependent degradation through the proximity effect between the target protein and AhR. β-NF-JQ1 acts as an antiproliferative and cytotoxic agent that induces anticancer activity associated with BRD protein knockdown. β-NF-JQ1 can be used for research on breast cancer and neuroblastoma.

SNIPER (BRD)-1 is a BRD2/3/4 SNIPER degrader. SNIPER (BRD)-1 induces ubiquitin-proteasome-dependent degradation of the epigenetic regulatory proteins BRD2/3/4 as well as the IAP family E3 ligase itself with its IC₅₀ values for cIAP1, cIAP2 and XIAP of 6.8 nM, 17 nM and 49 nM, respectively. SNIPER (BRD)-1 can be used in the research of prostate cancer.

CFT-1297 is a CRBN-recruiting BRD4 PROTAC degrader with a DC₅₀ of 5 nM; it has K_D values of 2.1 μM, 0.68 μM and 58 nM for CRBN, BRD4 (BD2) and BRD4 (BD1), respectively. CFT-1297 binds weakly to CRBN-DDB1, with a K_D value of 2.1 μM.

DP-15 is a BRD4 and GSPT1 PROTAC degrader with DC₅₀ values of 0.48 nM and 5.25 nM, respectively. DP-15 induces ubiquitination and degradation of BRD4 and GSPT1. DP-15 induces Apoptosis. DP-15 exerts anticancer activity against acute myeloid leukemia and non-Hodgkin's lymphoma cells. DP-15 can be used in studies related to acute myeloid leukemia and non-Hodgkin's lymphoma.

CCW 28-3 is a BRD4 PROTAC degrader. CCW 28-3 recruits RNF4 to BRD4, inducing RNF4-dependent ubiquitination and proteasomal degradation of BRD4. CCW 28-3 can be used in breast cancer-related research.

ML 2-14 is a PROTAC targeting BRD4 with a C4 alkyl linker. ML 2-14 consists of the E3 ligase ligand EN219 (HY-115715) (bule part), the target protein ligand JQ-1 (HY-13030) (red part), and the PROTAC linker (balck part). ML 2-14 can effectively degrade BRD4 in 231MFP breast cancer cells, and this effect can be reversed by the proteasome inhibitor Bortezomib (HY-10227) and the E1 activase inhibitor TAK-243 (HY-100487). ML 2-14 can be used for breast cancer-related research.

PROTAC BRD4 Degrader linker conjugate is a linker-payload conjugate as well as a bifunctional degrader of BRD4 that binds to VHL, consisting of PROTAC and a linker. PROTAC BRD4 Degrader linker conjugate can be conjugated with STEAP1 and CLL1 antibodies to degrade BRD4 protein, with DC₅₀ values of 0.86 nM and 7.6 nM, respectively. PROTAC BRD4 Degrader linker conjugate can be used in research related to prostate cancer and acute myeloid leukemia (BRD4 ligand: (HY-129939); VHL ligand: (HY-125845)).\n