Epigenetic Reader Domain Degrader

PROTAC BET Degrader-14 is a highly efficient PROTAC targeting BET (bromodomain and extra-terminal domain). PROTAC BET Degrader-14 can degrade all BET (BRD2, BRD3, BRD4) family proteins. PROTAC BET Degrader-14 potently degrades BET proteins in U2OS osteosarcoma cell lines (BRD4 DC₅₀ = 130 nM) and KYSE180 esophageal squamous cell carcinoma cell lines (DC₅₀ = 40 nM). PROTAC BET Degrader-14’s dependence on the ubiquitin-proteasome system. PROTAC BET Degrader-14 decreases levels of BET-regulated gene products c-Myc, RUNX2, and KRT14. PROTAC BET Degrader-14 can be used for the study of osteosarcoma.

JP-2-196 is a molecular glue that covalently targets the RING family E3 ligase RNF126. JP-2-196 also binds to RNF40, MID2, RNF219, RNF14, and LRSAM1. JP-2-196 induces the formation of ternary complexes between RNF126 and target proteins (e.g., BRD4, AR-V7), thereby promoting their ubiquitination and proteasomal degradation. JP-2-196 has potential for cancer research (such as prostate cancer and leukemia).

BRD4 RIMTAC-1 is a BRD4 PROTAC degrader based on the RIPK1-mediated targeted chimera (RIMTAC) technology. It hijacks the endogenous RIPK1-VHL complex via the RIPK1 inhibitor moiety to indirectly recruit the VHL E3 ligase, forming a BRD4-Compound 10-RIPK1-VHL quaternary complex, and degrades BRD4 through the ubiquitin-proteasome system (UPS). BRD4 RIMTAC-1 exhibits selectivity over other BET proteins, induces concentration- and time-dependent, reversible post-translational degradation of BRD4 without altering the target mRNA level. BRD4 RIMTAC-1 potently induces endogenous BRD4 degradation in RAW264.7 and HEK-293T cells, with DC₅₀ values of 179.1 nM and 54.12 nM, respectively. BRD4 RIMTAC-1 can be used for the research of cancer and inflammation-related diseases.

JP-2-196 hydrochloride is a molecular glue that covalently targets the RING family E3 ligase RNF126. JP-2-196 hydrochloride also binds to RNF40, MID2, RNF219, RNF14, and LRSAM1. JP-2-196 hydrochloride induces the formation of ternary complexes between RNF126 and target proteins (e.g., BRD4, AR-V7), thereby promoting their ubiquitination and proteasomal degradation. JP-2-196 hydrochloride has potential for cancer research (such as prostate cancer and leukemia).

PROTAC BET Degrader-18 is a PROTAC targeting BET, with a DC₅₀ of 0.676 nM in HEK293-BRD4-HiBiT-KI cells. PROTAC BET Degrader-18 mainly targets and degrades BRD4 (EC₅₀ = 59.91 nM), and exhibits weak degradation activity against BRD2. PROTAC BET Degrader-18 inhibits the expression of downstream oncoprotein c-Myc, thereby inducing cell cycle arrest and apoptosis, while suppressing oncoprotein expression. PROTAC BET Degrader-18 shows antiproliferative activity against acute myeloid leukemia cells and triple-negative breast cancer cells. PROTAC BET Degrader-18 demonstrates antitumor efficacy in xenograft mouse models. PROTAC BET Degrader-18 can be used for the research of acute myeloid leukemia and triple-negative breast cancer.

Hsp70TAC BRD4 Degrader-1 is a degrader targeting BRD4, with a K_D value of 0.22 μM. Hsp70TAC BRD4 Degrader-1 forms a ternary complex with Hsp70 (K_D: 5.13 μM), and specifically and efficiently degrades intracellular BRD4 via the ubiquitin-proteasome pathway. Hsp70TAC BRD4 Degrader-1 exhibits potent anti-tumor proliferative activity. Hsp70TAC BRD4 Degrader-1 can be used in studies related to triple-negative breast cancer and glioblastoma multiforme. (Pink: BRD4 ligand (HY-78695); Blue: HSP70 ligand (HY-182979); Black: linker (HY-B0236)).

AB3067 is a PROTAC degrader of BET that simultaneously recruits the E3 ligase activities of CRBN and VHL. The DC₅₀ values of AB3067 against BRD2, BRD3, BRD4^Short and BRD4^Long are 15 nM, 1.6 nM, 2.1 nM and 2.3 nM, respectively. AB3067 induces additive protein ubiquitination and proteasomal degradation, and minimizes the cross-degradation of E3 ligases. AB3067 can be used in colon cancer-related studies.

dBET6 (Standard) is the analytical standard of dBET6 (HY-112588). This product is intended for research and analytical applications. dBET6 is a highly potent, selective and cell-permeable PROTAC connected by ligands for Cereblon and BET, with an IC₅₀ of 14 nM, and has antitumor activity.

ARV-771 (Standard) is the analytical standard of ARV-771 (HY-100972). This product is intended for research and analytical applications. ARV-771 is a BET PROTAC degrader, with K_d values of 34, 4.7, 8.3, 7.6, 9.6 and 7.6 nM against BRD2 (1), BRD2 (2), BRD3 (1), BRD3 (2), BRD4 (1) and BRD4 (2) , respectively. ARV-771 inhibits the transcription of AR/AR-v7 and its downstream target genes. By degrading BRD4 protein, ARV-771 enhances the sensitivity of prostate cancer cells to ferroptosis, suppresses cancer cell viability, and induces apoptosis. ARV-771 downregulates the levels of BRD4, c-MYC and AR-V7 in tumor tissues and inhibits tumor tissue growth. ARV-771 can be used in prostate cancer-related research.

BI-7273 acid, BI-7273 (HY-100351) derivative, is a BRD9 PROTAC ligand. BI-7273 acid can be conjugated with E3 ligase Ligand Thalidomide (HY-14658) and linker to synthesize BRD9 PROTAC degrader dBRD 9-A (HY-148739).

BRD4 degrader-8 is a BRD4-targeting degrader. BRD4 degrader-8 induces degradation of BRD4 protein via the ubiquitin-proteasome pathway. BRD4 degrader-8 can be used for the research of hematologic tumors, gastrointestinal stromal tumors, histiocytic lymphoma, non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell carcinoma, colorectal cancer, kidney cancer, gastric cancer, head and neck cancer, nasopharyngeal cancer.