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 selective HDAC8 PROTAC degrader with a DC₅₀ of 0.58 μM. SZUH280 recruits the CRBN E3 ubiquitin ligase to mediate polyubiquitination and proteasomal degradation of HDAC8, and exhibits higher selectivity for HDAC8 over other HDAC family members. SZUH280 induces apoptosis and G2/M cell cycle arrest in cancer cells. SZUH280 impairs DNA damage repair and promotes radiosensitization in cancer cells. SZUH280 inhibits the proliferation of cancer cells. SZUH280 is used in research related to lung cancer and breast cancer.

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 PROTAC degrader targeting HDAC6, with a DC₅₀ of 19.39 nM in HL-60 leukemia cells. PROTAC HDAC6 degrader 11 can form a ternary complex with HDAC6 and the cereblon E3 ligase, inducing polyubiquitination and proteasomal degradation of HDAC6. PROTAC HDAC6 degrader 11 inhibits the enzymatic activity of HDAC1 and does not trigger HDAC1 degradation. PROTAC HDAC6 degrader 11 induces hyperacetylation of α-tubulin. PROTAC HDAC6 degrader 11 can be used in related research on leukemia.

HD-TAC7 is a selective HDAC3 PROTAC degrader with an IC₅₀ of 1.1 μM. By recruiting the CRBN E3 ligase, HD-TAC7 induces ubiquitin-proteasome degradation and selective downregulation of HDAC3, which in turn increases H3K27 acetylation levels and downregulates the NF-κB subunit p65, exerting anti-inflammatory activity. HD-TAC7 is used in research on COVID-19, SARS-CoV-2 infection, asthma, chronic obstructive pulmonary disease, and colon cancer.

PROTAC HDAC degrader-2 TFA is a selective class IIb dual histone deacetylase (HDAC6 and HDAC10) PROTAC degrader, with DC₅₀ values of 13 nM and 29 nM against HDAC6 and HDAC10, respectively. It does not degrade class I (HDAC1/8) and class IIa (HDAC4/7) histone deacetylases.

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 class IIb dual histone deacetylase (HDAC6 and HDAC10) PROTAC degrader, with DC₅₀ values of 13 nM and 29 nM against HDAC6 and HDAC10, respectively. It does not degrade class I (HDAC1/8) and class IIa (HDAC4/7) histone deacetylases.

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.

HDAC6 degrader-6 is a HyT degrader targeting HDAC6, with a DC₅₀ of 6.357 μM in MOLT-4 cells. HDAC6 degrader-6 induces apoptosis. HDAC6 degrader-6 can be used for research on leukemia.

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 is a HDAC6 PROTAC degrader that recruits CRBN, and also a photoactivatable photochemical targeting chimeric (PHOTAC). PROTAC HDAC6 degrader 6 switches between cis and trans conformations upon illumination, in which the cis conformation binds HDAC6 and CRBN to form a ternary complex, and induces HDAC6 degradation via ubiquitin-like modification, polyubiquitination and proteasomal pathways. PROTAC HDAC6 degrader 6 can be used in the research of multiple myeloma.

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).