BRD4 Degrader

ZnPc-O3-JQ1 is a photoactivatable BRD4-targeting degrader and photosensitizer, composed of monosubstituted amino zinc phthalocyanine (ZnPc), the BRD4 ligand JQ1, and a PEG linker. Upon activation by light, ZnPc-O3-JQ1 generates reactive oxygen species (ROS) and induces BRD4 degradation in an E3 ubiquitin ligase-independent manner. BRD4 degradation further reduces HIF-1α and GCL levels and restricts the SLC7A11/GSH-related antioxidant response, thereby enhancing photodynamic therapy-associated oxidative stress. ZnPc-O3-JQ1 can be used in research related to bladder cancer.

JQ-1 (carboxylic acid)-amine-PEG8-cyanogen is a Target Protein Ligand-Linker Conjugate that incorporates a ligand for BRD4 (HY-78695) and a PROTAC linker, which recruits E3 ligases. JQ-1 (carboxylic acid)-amine-PEG8-cyanogen can be used for the synthesis of PROTAC BET Degrader-14 (HY-179588 ).

BRD4 degrader-6 is a dimeric BDR4 PROTAC degrader (DC₅₀: < 0.1 μM). BRD4 degrader-6 promotes the ubiquitination and degradation of BDR4 and has anticancer activity.

SJH1-51B is a SKP1-recruiting BRD4 PROTAC degrader. SJH1-51B binds to SKP1 in the SKP1-FBXO7-CUL1-RBX1 complex, but shows no or weak binding to monomeric SKP1. SJH1-51B induces proteasome- and SKP1-dependent degradation of BRD4, and this degradation process relies on the neddylation modification of Cullin-RING E3 ligase. SJH1-51B induces proteasome-mediated degradation of the short isoform of BRD4 in non-cancer cells, while it induces proteasome-mediated degradation of both the long and short isoforms of BRD4 in breast cancer cells. SJH1-51B can be used for breast cancer research.

PROTAC BRD4 Degrader-33 is a BRD4 PROTAC degrader that recruits CRBN. PROTAC BRD4 Degrader-33 downregulates PD-L1 expression, inhibits tumor cell proliferation and tumor growth in mice by inducing ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-33 can be used in the research of breast cancer.

PROTAC BRD4 Degrader-21 is a BRD4-targeting PROTAC degrader with an IC₅₀ value of 59 nM. PROTAC BRD4 Degrader-21 induces ubiquitination of BRD4, leading to its degradation via the proteasome. PROTAC BRD4 Degrader-21 binds to recombinant HSP90α protein with moderate affinity, having an IC₅₀ of 100-1000 nM. PROTAC BRD4 Degrader-21 induces cancer cell death. PROTAC BRD4 Degrader-21 inhibits tumor growth in xenograft mouse models. PROTAC BRD4 Degrader-21 can be used for the research of acute myeloid leukemia, diffuse large B-cell lymphoma.

BRD4 ligand 17 is the target protein ligand of BRD4 RIMTAC-1 (HY-187390). BRD4 RIMTAC-1 is a BRD4 PROTAC degrader based on RIPK1-mediated targeted chimeric (RIMTAC) technology, which can be used for research on cancer and inflammation-related diseases.

BRD-SF2 is a BRD4-targeted PROTAC degrader (DC₅₀: 17.2 μM) (Blue: VHL ligand, black: linker, pink: BRD4 ligand).

PROTAC BRD4 Degrader-48 is a BRD4 degrader with a K_d of 0.69 μM for human BRD4 and a DC₅₀ of 0.21 μM. PROTAC BRD4 Degrader-48 binds to BRD4 and GID4 to form a ternary complex, and induces ubiquitination and degradation of BRD4 via the ubiquitin-proteasome pathway. PROTAC BRD4 Degrader-48 inhibits proliferation and migration of tumor cells, blocks tumor growth, and maintains degrading activity even in VHL- and CRBN-deficient models. PROTAC BRD4 Degrader-48 can be used in studies related to renal cell carcinoma.

PROTAC CBP/p300/BRD4 Degrader-1 is a dual-target PROTAC degrader with DC₅₀ values of 8.8 pM (BRD4), 6.55 nM (CBP), and 1.05 nM (p300). PROTAC CBP/p300/BRD4 Degrader-1 induces CRBN- and proteasome-dependent degradation of BRD4 and CBP/p300, downregulates c-Myc and acetyl-H3K27, induces apoptosis. PROTAC CBP/p300/BRD4 Degrader-1 acts as an antiproliferative and antitumor agent, induces tumor growth inhibition in xenograft models. PROTAC CBP/p300/BRD4 Degrader-1 can be used for the research of prostate cancer and colorectal cancer.

PROTAC BRD4 Degrader-46 is a heterobifunctional BRD4 PROTAC degrader. PROTAC BRD4 Degrader-46 binds to both BRD4 and CRBN, thereby triggering ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-46 downregulates the levels of downstream BRD2, BRD3 and MYC. PROTAC BRD4 Degrader-46 can be used in the research of cancers such as multiple myeloma.

RAJQ14 is a BRD4 PROTAC-like CAP-TAC (Proteasome Cap Targeting Chimeras) degrader. RAJQ14 binds to 19S proteasome cap subunits RPN1, RPN10, RPN13, and USP14 to recruit target proteins to the proteasome for ubiquitination-independent, proteasome-dependent degradation. RAJQ14 can be used for the research of cancer (Pink: BRD4 Ligand (HY-181496); Blue: Proteasome Ligand (HY-128978); Black: Linker).

KBD-1 is a muscle-specific BRD4 PROTAC degrader with human K_Ds of 27.04 nM and 37.36 µM against BRD4 and KLHL4L, respectively. KBD-1 recruits the muscle-specific E3 ligase KLHL41, mediating Cullin-RING ligase (CRL)-dependent ubiquitination and proteasome degradation of BRD4. KBD-1 can be used for the research of myosarcoma.

BD-7148 is a potent, highly selective BRD4 PROTAC degrader with a DC₅₀ of 0.9 nM. BD-7148 binds to recombinant human BRD2-BD1, BRD2-BD2, BRD3-BD1, BRD3-BD2, BRD4-BD1 and BRD4-BD2 domain proteins, with K_d values ranging from 26 nM to 240 nM, and shows no binding preference for BRD4 domains over BRD2 or BRD3 domains. BD-7148 inhibits the growth of leukemia and breast cancer cells. BD-7148 can be used in the research of leukemia and breast cancer.

BRD4 degrader-7 (Compound ZZ1) is a CTLH-dependent BRD4 degrader and c-Glue with a DC₅₀ of 489 nM. BRD4 degrader-7 converts to a sulfinic acid derivative inside cells, interacts with the basic pocket of YPEL5, mediates the bridging of BRD4 BD1 to the YPEL5 subunit of the CTLH E3 ubiquitin ligase, and thereby promotes the formation of a ternary complex. BRD4 degrader-7 can be used in research on Ewing's sarcoma and leukemia.

MrTAC-8, methylarginine-targeting chimera (MrTAC), is a BRD4 degrader with DC₅₀ values of 46 nM in HeLa cells. MrTAC-8 recruits PRMT1, PRMT3, PRMT4, PRMT5, and PRMT7 to target proteins, inducing arginine methylation that triggers lysosomal degradation. MrTAC-8 degrades proteins across diverse subcellular localizations and independent of native proteolytic routes. MrTAC-8 can be used for the research of cervical cancer, glioblastoma.

PROTAC BRD4 Degrader-42 (Compound P6) is a PROTAC-based BRD4 degrader with a DC₅₀ of 1.11 μM. PROTAC BRD4 Degrader-42 promotes the ubiquitination and degradation of BRD4. PROTAC BRD4 Degrader-42 downregulates c-Myc expression and induces Apoptosis by upregulating BAD and BAX protein expression. PROTAC BRD4 Degrader-42 also exhibits anticancer activity against myeloid monocytic leukemia.

SJ44236 is a BET PROTAC degrader with activity against BRD2, BRD3 and BRD4 (DC₅₀ = 127 pM). SJ44236 induces ubiquitination and proteasomal degradation by forming a ternary complex with BET proteins and CRBN-DDB1. SJ44236 downregulates c-Myc, upregulates p53 and reduces cancer cell viability. SJ44236 can be used for the research of leukemia and medulloblastoma.

PROTAC BRD4 Degrader-38 is a BRD4 PROTAC degrader with DC₅₀ values of 86 nM and 106 nM against the short and long isoforms of BRD4, respectively. PROTAC BRD4 Degrader-38 covalently binds to the Cys232 residue of TRIM28 to form a ternary complex containing BRD4, thereby promoting the ubiquitination and degradation of BRD4. PROTAC BRD4 Degrader-38 can be used in the research of acute myeloid leukemia.

NEP162 is a BRD4 PROTAC degrader based on the E3 ubiquitin ligase GID4, with DC₅₀ values of 1.2 μM and 1.6 μM in SW480 and U2OS cells, respectively, and a K_d value of 0.13 µM for GID4. NEP162 bridges the E3 ligase GID4 and BRD4 to form a ternary complex, promotes polyubiquitination and subsequent degradation of BRD4 via the ubiquitin-proteasome system, reduces the proliferation capacity of tumor cells and induces apoptosis. NEP162 can be used for research on cancers such as osteosarcoma, colorectal cancer and non-small cell lung cancer.