Epigenetic Reader Domain Degrader

PROTAC BRD9 Degrader-12 is a BRD9 PROTAC degrader, with DC₅₀ values of 57 pM and 62 pM against BRD9 and IKZF1, respectively. PROTAC BRD9 Degrader-12 promotes CRL-CRBN-dependent ubiquitination and proteasome-mediated BRD9 degradation by simultaneously binding to BRD9 and CRBN, and concurrently recruits IKZF1 as a neosubstrate via CRBN to induce its degradation. PROTAC BRD9 Degrader-12 selectively degrades BRD9 and IKZF1. The synergistic degradation of BRD9/IKZF1 downregulates MYC-related signaling, induces apoptosis and S-phase cell cycle arrest, and thereby inhibits the proliferation of hematological malignant cells. PROTAC BRD9 Degrader-12 is used for research related to hematological malignancies.

PROTAC FLT3/JAK2/BRD4 Degrader-1 is a FLT3/JAK2/BRD4 PROTAC degrader with DC₅₀ values of 5.23, 0.68, and 1.17 nM, respectively. PROTAC FLT3/JAK2/BRD4 Degrader-1 induces cereblon- and proteasome-dependent degradation of FLT3, JAK2, and BRD4 via the ubiquitin-proteasome system. PROTAC FLT3/JAK2/BRD4 Degrader-1 is used in studies related to FLT3 inhibitor-resistant leukemia and acute myeloid leukemia.

PROTAC BRD4 Degrader-26 is a light-regulated BRD4 PROTAC degrader. PROTAC BRD4 Degrader-26 induces targeted degradation of BRD4 via the ubiquitin-proteasome system. PROTAC BRD4 Degrader-26 is a degrader that can be inactivated in response to ultraviolet light. PROTAC BRD4 Degrader-26 can be used in breast cancer-related research.

phoBET1 is a photolabile PROTAC molecule that, upon photoactivation, functions as a BRD4 PROTAC degrader to trigger BRD4 degradation via the ubiquitin-proteasome system. Activated phoBET1 induces cancer cell apoptosis and inhibits tumor growth in xenograft mouse models. In its inactive caged state, phoBET1 exhibits only extremely low antiproliferative activity against cancer cells. phoBET1 can be applied in studies related to acute myeloid leukemia.

PROTAC BRD4 Degrader-17 (compound 13i) is a potent PROTAC BRD4 Degrader, with IC₅₀ values of 29.54 nM (BRD4 (BD1)) and 3.82 nM (BRD4 (BD2)). PROTAC BRD4 Degrader-17 significantly attenuates G2/M progression associated Cyclin B1 expression. PROTAC BRD4 Degrader-17 significantly induces apoptosis in MV-4-11 cells.

PROTAC BRD3 degrader-1 (compound D072) is a potent and selective PROTAC BRD3 degrader. PROTAC BRD3 degrader-1 selectively degrades BRD3 in mice, leading to the downregulation of H3K18ac without affecting BRD2 or BRD4. PROTAC BRD3 degrader-1 reduces intraocular inflammation in the experimental autoimmune uveitis (EAU) mouse mode and inhibits proinflammatory microglia in both uveitis retina and LPS (HY-D1056) treated mouse microglia cell line BV2. PROTAC BRD3 degrader-1 can be used for uveitis research.

TKP-5 is a PROTAC protein degrader targeting BRD4. TKP-5 can binds to BRD2, BRD3, BRD4 and BRDT, with K_d values of 150 nM, 100 nM and 150 nM for the first three proteins respectively. TKP-5 inhibits the production of thymic stromal lymphopoietin and suppresses the expression of IL-33 mRNA. TKP-5 is applicable to studies related to tape-stripping induced skin injury.

ZZ7-23-022 (ZZ7) is a selective BRD9 molecule glue degrader. ZZ7-23-022 effectively degrades BRD9 in synovial sarcoma cells, but does not affect cardiomyocytes. ZZ7-23-022 can be used for the research of cancer.

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.

BTR2038 is a BTR2000-based heterobifunctional PROTAC that induces the degradation of BRD9 by recruiting the CUL3^KLHL20 E3 ubiquitin ligase. BTR2038 consists of a BRD9 bromodomain ligand derived from a BI-7273 analog, a linker, and the macrocyclic KLHL20 ligand BTR2000. BTR2038 is applicable for research related to KLHL20-recruited targeted protein degradation and BRD9 modulation.

BI 7271 is a BRD9 ligand, which can be used for the synthesis of PROTACs, such as PROTAC BRD9 Degrader-7 (HY-155361).

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 ).

Cath-L-dBET1 is a PROTAC degrader targeting BRD4. Cath-L-dBET1 has an IC₅₀ value of 2.8 μM in MDA-MB-231 cells. Cath-L-dBET1 can be activated by cathepsin L (Cath-L) and recruit the E3 ubiquitin ligase and degrade BRD4 through ubiquitin-proteasome system. Hyp-dBET1 can be used for anti-tumor study.

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.