HDAC1 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.

PROTAC HDAC6 degrader 11 is a potent and selective HDAC6 degrader via ternary complex formation and the ubiquitin-proteasome pathway with a DC₅₀ value of 19.4 nM. PROTAC HDAC6 degrader 11 has IC₅₀s of 4.54 nM and 0.647 μM for HDAC6 and HDAC1, respectively. PROTAC HDAC6 degrader 11 causes strong hyperacetylation of α-tubulin.

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.

Naph-Se-TMZ is a PROTAC-like HDAC1 degrader. Naph-Se-TMZ induces ROS-dependent reduction in HDAC1 protein expression and total HDAC activity, and decreases cell viability in a dose-dependent manner. Naph-Se-TMZ exhibits activity in both TMZ-sensitive and TMZ-resistant glioma cells, and its cytotoxicity is reversed by the ROS scavenger N-acetylcysteine (HY-B0215). Naph-Se-TMZ can be used in studies related to glioblastoma.
Naph-Se-TMZ consists of a target protein ligand (red segment): Temozolomide (HY-17364), a DNA intercalator (blue segment): Nitro-Naphthalimide-C2-acylamide (HY-169437), and a molecular linker (black segment). Meanwhile, the activity control for the target protein ligand is Temozolomide-amino hydrochloride (HY-169439), and the DNA intercalator+linker is NNISC-2 (HY-169438).

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 HDAC6 degrader (Compound A6) is a potent and selective PROTAC HDAC6 degrader with a DC₅₀ of 3.5 nM. PROTAC HDAC6 degrader shows promising antiproliferative activity via inducing apoptosis in myeloid leukemia cell lines.

HDAC degrader-2 is a selective HDAC degrader with a DC₅₀ values of 2.55 μM against HDAC1. HDAC degrader-2 effectively induces the degradation of HDAC1 and HDAC2, but has no significant effect on the degradation of HDAC3, 4, 6 and 8. HDAC degrader-2 exerts potent antiproliferative effects against MM.1S and MCF-7 cells. HDAC degrader-2 induces apoptosis in myeloma cells. HDAC degrader-2 can be used for the study of myeloma.

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))