Epigenetic Reader Domain Degrader

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.

EN884 is a BRD4 degrader via a SKP1- and proteasome-dependent manner. EN884 can be used in synthetic proteolysis targeting chimeras (PROTACs).

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.

BRD9 Degrader-2 is a selective BRD9 molecular glue degrader. BRD9 Degrader-2 consists of a BRD9-binding ligand, a linker, and a warhead that promotes proteasomal degradation of BRD9 via a non-canonical PROTAC mechanism independent of CRBN or VHL E3 ligases. BRD9 Degrader-2 can be used in cancer research, including studies of malignant rhabdoid tumors, specific sarcomas, and acute myeloid leukemia.

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.

DAO-dBET1 is a Dual-Action-Only PROTAC containing a PROTAC degrader, dBET1 (HY-101838). DAO-dBET1 is a potent BRD4 degrader with a DC₅₀ value of 277 nM in the presence of CoCl₂. DAO-dBET1 inhibits hypoxia and Cath-L trigger with an IC₅₀ value of 281 nM.

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.

EBET-1593 is a BET PROTAC degrader. EBET-1593 can promote the ubiquitination and degradation of BET. EBET-1593 is a lead payload. EBET-1593 can be used to synthesize ADCs, such as 84-EBET. 84-EBET has antitumor effects against pancreatic ductal adenocarcinoma.

dBAZ2 is a first-in-class BAZ2A and BAZ2B PROTAC degrader with DC₅₀ values of 180 nM and 250 nM for BAZ2A and BAZ2B, respectively. (Blue: E3 ligase ligand (VH 101, thiol (HY-47851); Black: linker (HY-168450); pink: target protein ligand (HY-168449)).

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.

PROTAC AR/BET protein degrader-1 (Compound 149) is an Androgen Receptor and BET (bromodomain and extra-terminal domain) protein degrader that can be used in cancer research.

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.

PROTAC BRD9 Degrader-11 is a VHL-based BRD9 PROTAC degraderwith an IC₅₀ of 0.66 μM. PROTAC BRD9 Degrader-11 induces selective, proteasome-dependent degradation of BRD9 via the ubiquitin-proteasome system. PROTAC BRD9 Degrader-11 impairs cell viability, suppresses proliferation, and arrests growth of acute myeloid leukemia cells. PROTAC BRD9 Degrader-11 can be used for the research of acute myeloid leukemia.

PROTAC BRD4 Degrader-20 (Compound 195) is a PROTAC degrader that targets BRD4 for degradation by recruiting VHL. PROTAC BRD4 Degrader-20 is applicable to the research of diffuse large B-cell lymphoma.

PROTAC BRD3/BRD4-L degrader-2 is a PROTAC molecule and can selectively degrade cellular BRD3 and BRD4-L with K_i values of 16.91 and 2.8 nM, respectively. PROTAC BRD3/BRD4-L degrader-2 also has robust antitumor activity in mouse xenograft models. PROTAC BRD3/BRD4-L degrader-2 can be used for the research of cancer.