HDAC3 Degrader

Thalidomide-4-OH (Cereblon ligand 2) is the Thalidomide-based Cereblon ligand used in the recruitment of CRBN protein. Thalidomide-4-OH (Cereblon ligand 2) can be connected to the ligand for protein by a linker to form PROTACs.

YX968 is a selective HDAC3/HDAC8 PROTAC dual degrader, with a DC₅₀ value of 1.7 nM against HDAC3 and 6.1 nM against HDAC8. YX968 inhibits cancer cell growth, induces apoptosis, prevents global histone hyperacetylation, and exerts effects via antiproliferative activity. YX968 can be used in research related to triple-negative breast cancer, non-small cell lung cancer, and multiple myeloma.

HD-TAC7 is a potent PROTAC HDAC degrader with IC₅₀ values of 3.6 μM, 4.2 μM and 1.1 μM for HDAC1, HDAC2 and HDAC3, respectively. HD-TAC7 can decreases NF-κB p65 in RAW 264.7 macrophages. HD-TAC7 can be used for the research of inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD).

FF2049 is a selective HDAC1-3 PROTAC degrader (with a DC₅₀ of 257 nM against HDAC1). FF2049 recruits the E3 ligase FEM1B to mediate ubiquitination and proteasomal degradation of HDAC1-3. FF2049 induces cell cycle arrest and Apoptosis in cells. FF2049 can be used in research related to multiple myeloma, acute monocytic leukemia, triple-negative breast cancer and glioblastoma.

JPS035 is a HDAC1, HDAC2 and HDAC3 PROTAC degrader, with a DC₅₀ value of 3.58 μM against HDAC1 and 1.38 μM against HDAC3. JPS035 recruits the VHL E3 ligase to mediate the ubiquitination and degradation of HDAC1, HDAC2 and HDAC3. JPS035 increases the acetylation level of histone H3 lysine 56 and regulates global gene expression. JPS035 can be used in colon cancer-related research.

HDAC3 degrader-1 (Compound Z8) is a selective HDAC3 degrader with a DC₅₀ of 2.42 μM. HDAC3 degrader-1 has almost no effect on HDAC1, HDAC2, and HDAC6. HDAC3 degrader-1 inhibits the activation of the NLRP3 inflammasome and reduces the secretion of IL-1β and caspase-1. HDAC3 degrader-1 shows significant efficacy in septic shock and colitis models. HDAC3 degrader-1 can be used in anti-inflammatory research.

JPS004 is a HDAC1-3 PROTAC degrader. JPS004 can induce degradation of HDAC1-3 and induce histone acetylation. JPS004 can induce cancer cells apoptosis. JPS004 can be used for the research of cancer.

PROTAC HDAC8 Degrader-2 is a HDAC6/8 PROTAC degrader, with IC₅₀ values of 0.042 μM and 0.147 μM against human HDAC8 and HDAC6, respectively, and exhibits selectivity over other class I HDAC isozymes. PROTAC HDAC8 Degrader-2 induces apoptosis (apoptosis) in leukemia cells, shows no obvious cytotoxicity to normal cells, and has favorable chemical stability. PROTAC HDAC8 Degrader-2 can be used in research related to acute myeloid leukemia.

PROTAC HDAC3 degrader-1 is a selective PROTAC degrader targeting HDAC3 with a DC₅₀ of 30.73 nM. PROTAC HDAC3 degrader-1 induces degradation of HDAC3 via the ubiquitin-proteasome system. PROTAC HDAC3 degrader-1 promotes apoptosis, induces DNA damage, and downregulates anti-apoptotic proteins Mcl-1 and Bcl-xL. PROTAC HDAC3 degrader-1 can be used for the research of acute myeloid leukemia.

PROTAC HDAC6 degrader 4 (Compound 17c) is the PROTAC degrader for HDAC6 with a DC₅₀ of 14 nM. PROTAC HDAC6 degrader 4 exhibits inhibitory activit against HDAC1, HDAC2, HDAC3 and HDAC6 with IC₅₀s of 2.2, 2.37, 0.61 and 0.295 μM, respectively. (Pink: ligand for target protein HDAC6 ligand-3 (HY-172360); Black: linker (HY-138387); Blue: ligand for cereblon E3 ligase (HY-W093272))