Epigenetic Reader Domain Degrader

TMU454 is an ASGPR-targeting GalNAc-PROTAC BRD4 degrader conjugate. TMU454 undergoes ASGPR-mediated endocytosis and CTSB cleavage to release MZ1, which selectively degrades BRD4 in ASGPR-positive hepatocellular carcinoma cells via the VHL/UPS/proteasome pathway. TMU454 inhibits cancer cell proliferation and colony formation, and suppresses tumor growth in vivo. TMU454 can be used for research related to hepatocellular carcinoma.

PROTAC BET Degrader-15 is a BET PROTAC degrader with DC₅₀ values of <0.10 nM, <0.01 nM, and <0.01 nM against BRD2, BRD3, and BRD4, respectively. PROTAC BET Degrader-15 induces significant G2/M phase cell cycle arrest and triggers apoptosis. PROTAC BET Degrader-15 causes marked downregulation of c-Myc, accompanied by upregulation of the cell cycle inhibitory protein p21, downregulation of CDK6, and an increase in the apoptosis marker cleaved PARP. PROTAC BET Degrader-15 is applicable to the research of hematologic malignancies and lung cancer.

EA-89 is a potent and selective BRD9 inhibitor with antitumor activity. EA-89 is a Ligand for Target Protein for PROTAC. EA-89 can be used to synthesize PROTAC QA-68 (HY-150797).

BRD4 degrader-5 (Compound 23) is a hydrophobic tag (HyTag)-based protein degrader for BRD4 (DC₅₀ = 24.7 μM) through ER stress and autophagy-lysosome pathway. BRD4 degrader-5 inhibits the proliferation of cancer cell 4T1 with an IC₅₀ of 20.6 μM.

PROTAC BRD4 Degrader-3 is a potent BRD4 PROTAC degrader with DC₅₀ values ​​of 164 nM and 80 nM at 4 h and 24 h, respectively. PROTAC BRD4 Degrader-3 induces the ubiquitination and subsequent proteasomal degradation of BRD4 by recruiting the ubiquitin E3 ligase KLHDC2. PROTAC BRD4 Degrader-3 can be used in breast cancer research.

GXF-111 is a BRD3 and BRD4-L PROTAC degrader. Its BD1 and BD2 Ki values against human BRD3 are 11.97 nM and 2.45 nM, respectively. The degradation activity of GXF-111 depends on its binding to BET proteins and Cereblon, as well as the involvement of a functional proteasome. The degradation selectivity of GXF-111 is mainly determined by differences in degradation kinetics and cell types. GXF-111 induces G₁ phase cell cycle arrest, downregulates c-Myc expression, upregulates p21 expression, and exhibits antiproliferative activity against a variety of cancer cell lines. GXF-111 can serve as a research tool for cancer-related studies.

iHAC is an inhibitor HSP90-anchoring chimera, that covalently binds BRD4 ligand (+)-JQ-1 to HSP90, and inhibits the proliferation of cancer cells. iHAC activates the anti-tumor immune response, inhibits the recurrence and metastasis of 4T1 breast cancer in mouse models.

JY-21 is a BRD4 PROTAC degrader active against both long and short BRD4 isoforms. JY-21 binds to TRIM28, RACK1, LMO7 and FUS to induce proteasomal degradation of BRD4 isoforms (DC₅₀: 5.944 μM for long BRD4 isoform; 3.797 μM for short BRD4 isoform). JY-21 is applicable to research related to triple-negative breast cancer.

RB-CO-PEG5-C2-CO-VH032 is a VHL-recruiting TRIM24 PROTAC degrader composed of an RB-derived short peptide SPRT, a PEG5-C2 linker, and the VHL ligand VH032. RB-CO-PEG5-C2-CO-VH032 recognizes proteins containing the FXXXV motif and recruits VHL to induce degradation of proteins such as TRIM24, thereby upregulating DUSP2, inhibiting ERK/mTOR signaling, and suppressing prostate cancer cell proliferation. RB-CO-PEG5-C2-CO-VH032 can be used for TRIM24 degradation and prostate cancer-related research.

PROTAC p300 degrader-1 is a paralog-selective, PROTAC-based degrader targeting the p300/CBP protein. It exhibits potent antiproliferative, cell cycle arrest and pro-apoptotic activities, and can be used in the research and development of antitumor drugs and related mechanism studies for hematological malignancies (AML, MM, NHL).

ZD-1-186 is a non-degradative, covalent-dependent molecular glue that targets BCL6 and BRD9. ZD-1-186 inhibits the transcriptional output of MYC, relieves the repression of canonical BCL6 target loci (including CDKN1A (p21)), and mediates the selective recruitment of BRD9 to BCL6. ZD-1-186 can be used for research on diffuse large B-cell lymphoma.

CFT-743, a PROTAC-based heterobifunctional degrader and BET inhibtor, is a degrader of BRD4 bromodomain 1 (BD1) with a DC₅₀ of 4.3 nM. CFT-743's antitumor activitiy is dependent on BET degradation and can be attenuated by Pomalidomide (HY-10984), which is a CRBN binding molecule. CFT-743 induces ubiquitination of BRD4 BD1. CFT-743 can be used for cancer research.

BRD9 Degrader-3 is a selective BRD9 BRD9 molecular glue degrader degrader. BRD9 Degrader-3 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-3 can be used in cancer research, including studies of malignant rhabdoid tumors, specific sarcomas, and acute myeloid leukemia.

PROTAC BRD4 Degrader-29 is a potent BRD4 PROTAC degrader with a DC₅₀ of 89.4 nM. PROTAC BRD4 Degrader-29 mediates proteasomal degradation of BRD4 by bridging BRD4 and the CRBN E3 ubiquitin ligase. PROTAC BRD4 Degrader-29 can be used in cancer research.

MS479 is a PROTAC degrader targeting BRD4, BRD3 and BRD2. MS479 recruits the E3 ligase SPOP by bridging the protein GLP, thereby promoting polyubiquitination modification and subsequent 26S proteasomal degradation. MS479 inhibits the proliferation of colorectal cancer cells and can be used for research on colorectal cancer and triple-negative breast cancer.

BRD9 Degrader-1 is a selective BRD9 PROTAC degrader with a DC₅₀ of 108 nM. BRD9 Degrader-1 induces the formation of a ternary complex between BRD9 and VHL, with an EC₅₀ of 17 nM, and shows no hook effect at high concentrations. BRD9 Degrader-1 can be used for the research of synovial sarcoma.

PROTAC BRD9 Degrader-8 is a selective, orally active BRD9 PROTAC degrader with a DC₅₀ of 16 pM.\nPROTAC BRD9 Degrader-8 induces cell cycle arrest at the G1 phase and promotes apoptosis. PROTAC BRD9 Degrader-8 can be used for research on acute myeloid leukemia and diffuse large B-cell lymphoma.

LO-3-61, a JQ-1 (HY-13030) analog bearing a truncated fumaramide handle, is a PROTAC (proteolysis-targeting chimeras)-like BRD4 degrader. LO-3-61 degrades both the long and short isoforms of BRD4 CUL4DcAr16-dependently in cells. LO-3-61 shows selectivity for BRD3 and BRD4 degradation in MDA-MB-231 cells.

BT-PROTAC is a bioorthogonally activatable BRD4/BRD3 PROTAC degrader prodrug. BT-PROTAC is inactive when present alone, but upon activation by tetrazine compounds, it promotes the degradation of BRD4 and BRD3 via the ubiquitin-proteasome system, inhibits c-Myc expression, activates caspase-3, and induces apoptosis in breast cancer cells. BT-PROTAC can be used for breast cancer research.

PROTAC BRD4 Degrader-43 is a BRD4 PROTAC degrader. PROTAC BRD4 Degrader-43 recruits the DCAF1-DDB1-Cul4A E3 ligase complex via a Vpr-derived peptide moiety to induce BRD4 ubiquitination and degradation through the ubiquitin-proteasome system. PROTAC BRD4 Degrader-43 exhibits potent HIV latency-reversing activity. PROTAC BRD4 Degrader-43 can be used for the research of HIV-1 latent infection. (Pink: BRD4 ligand (HY-13030); Blue: Cul4A-DDB1-DCAF1 ligand (HY-P11640); Black: conjugate of PEG linker + cell-penetrating peptide (HY-P2483))