BRD4 Degrader

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.

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.

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))

PROTAC BRD4 Degrader-3 is a VHL-recruiting PROTAC degrader that targets BRD4. PROTAC BRD4 Degrader-3 consists of a VHL E3 ubiquitin ligase ligand and a BRD4 inhibitor linked by a connector.

J594 is a BRD4 molecular glue degrader targeting RNF126, with DC₅₀ values of 0.077 μM (long-form BRD4 in HEK293T cells) and 0.26 μM (short-form BRD4 in HEK293T cells), respectively. J594 induces proteasome- and RNF126-dependent degradation of BRD4.

Pomalidomide-C5-Dovitinib is a heterobifunctional PROTAC that recruits KEAP1 E3 ligase to degrade BRD4 and BRD3, but not BRD2.

AB3145 is a selective Brd4 BromoTag PROTAC degrader (DC₅₀: 120-140 pM). AB3145 promotes the ubiquitination and degradation of Brd4. AB3145 can be used in cancer research.

NEP108 is a GID4 E3 ligase-based BRD4 PROTAC degrader, with its DC₅₀ value approximately 3.8 μM. NEP108 has a strong affinity for GID4, with a K_D value of 0.22 μM, and the K_D value of its trimeric complex is 2.85 μM. NEP108 can be used for cancer research.

PROTAC BRD4 Degrader-22 is a BRD4 PROTAC degrader with a DC₅₀ of 0.59 nM. At high concentrations, PROTAC BRD4 Degrader-22 induces partial degradation of BRD3 and BRD2, but exhibits selectivity for IKZF3. PROTAC BRD4 Degrader-22 can be used in leukemia-related research.

Hyp-dBET1 is a hypoxia-activated BRD4 PROTAC degrader. The IC₅₀ of Hyp-dBET1 for reducing cell viability under hypoxic conditions is approximately 153 nM to 192 nM, while it shows low activity under normoxic conditions (IC₅₀ of approximately 2.8 μM to 3.8 μM). Hyp-dBET1 induces BRD4 degradation under hypoxic conditions, converts to dBET1 in hypoxic environments, and downregulates the expression level of ZFP-91. Hyp-dBET1 can be used in studies related to breast cancer, cervical cancer and solid tumors.

PROTAC BRD4 Degrader-41 (Compound A5) is a BRD4 PROTAC degrader with a DC₅₀ of 0.97 nM. PROTAC BRD4 Degrader-41 exhibits potent anti-proliferative activity against various types of cancer cells such as AML, lymphoma, breast cancer, ovarian cancer, and non-small cell lung cancer. PROTAC BRD4 Degrader-41 can induce G0/G1 phase arrest and apoptosis in MV4-11 cells. PROTAC BRD4 Degrader-41 downregulates the transcriptional level of c-Myc.

PROTAC BRD4 Degrader-35 (Compound 17) is a PROTAC degrader targeting BRD4, which is formed by coupling a BRD4 inhibitor active moiety with an HSP90-binding fragment via a linker. PROTAC BRD4 Degrader-35 can be used in cancer-related research.

PROTAC BRD4 Degrader-39 is a selective targeting Bromodomain protein 4 (BRD4) degrader with an DC₅₀ value of 24.66 nM. PROTAC BRD4 Degrader-39 conjugates BRD PROTAC (ARV-771) (HY-100972) with carbohydrate. PROTAC BRD4 Degrader-39 selectively delivers to tumor cells with high GLUT1 expression, followed by GSH-triggered release of ARV-771 and degrades BRD4. PROTAC BRD4 Degrader-39 can inhibit tumor growth and show no significant toxicity. PROTAC BRD4 Degrader-39 can be used for the research of cancer, such as breast cancer.

ZX079 is a dual BRD4 and CBP PROTAC degrader with a BRD4 DC₅₀ value of 0.035 nM and a CBP DC₅₀ value of < 0.02 nM. ZX079 induces dose- and time-dependent degradation of BRD4 and CBP proteins through recruitment of the cereblon E3 ligase. ZX079 induces apoptosis in MV4-11 and MOLM-13 cells, reduces tumor growth in an acute myeloid leukemia xenograft model. ZX079 can be used for the research of acute myeloid leukemia.

K2-B4-3e is a BRD4 PROTAC degrader with a DC₅₀ of 66 nM. K2-B4-3e binds to KLHDC2 to form a ternary complex with BRD4, inducing degradation dependent on the ubiquitin-proteasome system. K2-B4-3e is applicable for cancer-related research.

PROTAC BRD4 Degrader-51 is a PROTAC-class degrader targeting BRD4, which degrades BRD4 via the ubiquitin-proteasome pathway. PROTAC BRD4 Degrader-51 degrades BRD4 (long) and BRD4 (short) isoforms with DC₅₀ values of 27.92 nM and 20.03 nM, respectively. PROTAC BRD4 Degrader-51 exhibits antiproliferative activity against tumor cells. It can be used in research related to various cancers such as leukemia and breast cancer.

Gal-ARV-771 is a galactose-modified derivative of ARV-771 (HY-100972). Gal-ARV-771 is activated in cells expressing SA-β-Gal, thereby releasing ARV-771. Gal-ARV-771 selectively induces Apoptosis. ARV-771 is a BET PROTAC degrader. Gal-ARV-771 can be used in the research of lung adenocarcinoma (Gal+linker: Gal-PAB (HY-188142); PROTAC: ARV-771 (HY-100972)).

JQ1-JX5 is a DCAF16-based BRD4 PROTAC degrader. JQ1-JX5 covalently modifies Cys58 of DCAF16, promotes ternary complex formation with BRD4, enables BRD4 ubiquitination and proteasomal degradation. JQ1-JX5 induces time-dependent degradation of BRD4 long and short isoforms in AGS cells with DC₅₀ of 43.97 and 16.77 nM. JQ1-JX5 can be used for the research of cancer, such as acute myeloid leukemia.