HDAC6 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.

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.

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.

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.

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.

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.

XY-09-36 is a HDAC8 PROTAC degrader with a DC₅₀ value of 30 nM (HEK 293T eGFP.HDAC8-IRES-mCherry reporter cells, 24 h). XY-09-36 binds HDAC8 and recruits VHL E3 ubiquitin ligase, inducing HDAC8 ubiquitination and proteasomal degradation; the IC₅₀ values of XY-09-36 against HDAC8 and HDAC6 are 2.03 μM and 7.21 μM, respectively. XY-09-36 selectively reduces the viability of STAG2-mutant Ewing sarcoma cells. XY-09-36 increases acetylated SMC3 levels. XY-09-36 can be used for research on Ewing sarcoma.

PROTAC HDAC6 degrader 12 is a PROTAC and a selective HDAC6 degrader consists of a non-selective HDAC inhibitor and thalidomide-type E3 ligase ligand. HDAC6 degrader-4 can be used for cancer research.

HDAC-IN-97 is a PROTAC HDAC6 degrader-6that can be used for synthesis of PROTACs, such as HDAC6 degrader-6 (HY-177758). HDAC6 degrader-6 is a potent HDAC6 PROTAC degrader with anticancer activity.

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.

HDAC1 Degrader-1 is a HDAC1 degrader with an IC₅₀ of 192.3 nM. HDAC1 Degrader-1 induces degradation of HDAC1 in multiple myeloma cells via the proteasome system and enhances apoptosis of multiple myeloma cells. HDAC1 Degrader-1 can be used for research on multiple myeloma.

YL633 is a selective CRBN-recruiting HDAC8 PROTAC degrader with DC₅₀ = 3.3 nM. YL633 binds to the CRBN E3 ubiquitin ligase and mediates HDAC8 degradation. YL633 inhibits HDAC3 enzymatic activity with IC₅₀ of 342.9 nM, and induces degradation of HDAC6 and HDAC7. YL633 inhibits DLBCL cell proliferation. YL633 can be used in research related to diffuse large B-cell lymphoma.

PROTAC HDAC6 degrader 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.

PROTAC HDAC6 degrader 8 is a potent and selective HDAC6 PROTAC degrader with a DC₅₀ of 1.94 nM. PROTAC HDAC6 degrader 8 induces HDAC6 degradation in cancer cells with a hook effect, and exerts no impact on other HDAC subtypes, IKZF1, IKZF3 or GSPT1. PROTAC HDAC6 degrader 8 can be used in studies related to multiple myeloma.

PROTAC HDAC6 degrader 10 is a highly efficient, safe and selective HDAC6 PROTAC degrader with a pIC₅₀ of 8.75 and a pDC₅₀ of 9.2 in BEAS-2B cells. PROTAC HDAC6 degrader 10 recruits cereblon to form a ternary complex with HDAC6, thereby achieving the degradation of HDAC6. PROTAC HDAC6 degrader 10 significantly induces hyperacetylation of α-tubulin without affecting the acetylation of H3, and achieves sustained HDAC6 knockdown in mouse lung tissues. PROTAC HDAC6 degrader 10 exhibits high bioavailability after subcutaneous administration in mice. PROTAC HDAC6 degrader 10 enables the study of HDAC6 pharmacology via chemical knockdown of HDAC6 in vitro and in vivo, and can be used for research on pulmonary diseases.

FF2039 is a pan-HDAC PROTAC degrader that binds to DCAF11, acting on HDAC6, HDAC1, HDAC2 and HDAC4. FF2039 recruits the DCAF11 E3 ligase and mediates the polyubiquitination and degradation of HDACs via the ubiquitin-proteasome system. FF2039 induces cell cycle arrest, apoptosis, cytotoxicity and antiproliferative activity in cancer cells, and reduces the clonogenic capacity of cancer cells. FF2039 is applicable to research related to multiple myeloma, triple-negative breast cancer and glioblastoma.