HDAC 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.

HDAC6 degrader-1 is the PROTAC degrader for HDAC6 with a DC₅₀ of 3.8 nM in cell MM.1S.

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.

TO-1187 TFA is a selective HDAC6 PROTAC degrader (DC₅₀: 5.81 nM). TO-1187 TFA promotes the ubiquitination and degradation of HDAC6 and can be used in the study of hematological malignancies and solid tumors.

SZUH280 is a potent and selective PROTAC HDAC8 degrader with a DC₅₀ of 0.58 μM in A549 cells. SZUH280 induces cancer cell apoptosis. SZUH280 hampers DNA damage repair in cancer cells, promoting cellular radiosensitization.

PROTAC HDAC6 degrader 3 is a selective HDAC6 PROTAC degrader with an IC₅₀ of 0.686 μM and shows high selectivity for HDAC6 over HDAC1-4. PROTAC HDAC6 degrader 3 recruits cereblon (CRBN) to trigger HDAC6 ubiquitination and subsequent proteasomal degradation. PROTAC HDAC6 degrader 3 selectively elevates acetylated α-tubulin levels in cancer cells, and does not induce histone H3 hyperacetylation or obvious loss of cell viability. PROTAC HDAC6 degrader 3 is applicable for research on multiple myeloma.

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).

PROTAC HDAC degrader-2 TFA is the trifluoroacetate salt of PROTAC HDAC degrader-2. PROTAC HDAC degrader-2 is a selective IIb HDACs PROTAC degrader, with DC₅₀s of 13 nM for HDAC6, 29 nM for HDAC10, respectively. PROTAC HDAC degrader-2 exhibits low cytotoxicity against hematological and solid cancer cell lines. PROTAC HDAC degrader-2 can be used for the chemical knockdown of class IIb HDACs.

TO-1187 is a selective HDAC6 PROTAC degrader with a DC₅₀ value of 5.81 nM. TO-1187 degrades HDAC6 via the ubiquitin-proteasome pathway. TO-1187 can be used in the research of multiple myeloma, neuroblastoma, and cervical cancer.

PROTAC HDAC degrader-2 is a selective IIb HDACs PROTAC degrader, with DC₅₀s of 13 nM for HDAC6, 29 nM for HDAC10, respectively. PROTAC HDAC degrader-2 exhibits low cytotoxicity against hematological and solid cancer cell lines. PROTAC HDAC degrader-2 can be used for the chemical knockdown of class IIb HDACs.

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.

HDAC6 ligand-5 is a binding ligand of HDAC6 and can be used to synthesize PROTACs such as PROTAC HDAC6 degrader 5.

Degrader-1 (compound Z16) is a potent and selective HDAC8 PROTAC degrader with an DC₅₀ of 0.27 nM in A549 cells.

PROTAC HDAC8 Degrader-3 (Compound BP6) is an efficient, selective and low-toxicity HDAC8 PROTAC degrader with a DC₅₀ of 80 nM. PROTAC HDAC8 Degrader-3 exhibits IC₅₀ of PROTAC for HDAC8 and CRBN of 0.26 and 30 μM respectively. PROTAC HDAC8 Degrader-3 increases the level of Ac-SMC3, stabilizes p53 and sensitizes targeted reagents (such as Idasanutlin (HY-15676)), demonstrating its great potential in combination therapy.

PROTAC HDAC6 degrader 6 (Compound 12) is a selective HDAC6-targeting photochemically targeting chimeras (PHOTACs) (subset of PROTAC) degrader with a ～50% D_max only upon activation to its cis-state with 390 nm light irradiation.

PROTAC HDAC6 degrader 9 is a selective HDAC6 PROTAC degrader. PROTAC HDAC6 degrader 9 can be used for the research cancers related to HDAC6 abnormalities, such as multiple myeloma.

Tubastatin A-C6-NHBoc is a conjugate of a target protein ligand and a linker, which can be used to synthesize PROTACs, such as PROTAC HDAC degrader-2 (HY-174444).

PROTAC HDAC8 Degrader-3 (Compound BP1) is an efficient and selective HDAC8 PROTAC degrader with a DC₅₀ of 20 nM. PROTAC HDAC8 Degrader-3 exhibits IC₅₀ for HDAC8 and CRBN of 0.46 and 7.5 μM, respectively. PROTAC HDAC8 Degrader-3 exhibits potent anti-proliferative activity against MM.1S and HL-60 cells. PROTAC HDAC8 Degrader-3 can be used for research on multiple myeloma and acute myeloid leukemia.