TO-1187

TO-1187 is a selective HDAC6 PROTAC degrader (DC₅₀: 5.81 nM). TO-1187 promotes the ubiquitination and degradation of HDAC6 and can be used in the study of hematological malignancies and solid tumors (Pink: HDAC6 ligand (HY-173386); Blue: CRBN ligase ligand (HY-41547); Black: linker (HY-140212))^[1]. In Vitro:TO-1187 (100 nM, 6 h) highly selectively degrades HDAC6 in human multiple myeloma cells (MM.1S) (D_max: 94%, DC₅₀: 5.81 nM)^[1].
TO-1187 (100 nM, 72 h) does not show significant antiproliferative activity in MM.1S cells, indicating that it has low toxicity^[1].
TO-1187 (1-10000 nM) also exhibits a dose-dependent HDAC6 degradation ability in HeLa cells^[1].
TO-1187 (100 nM, Pre-treatment for 1 h, then treatment for 6 h) HDAC6 is degraded by CRBN E3 ligase and proteasome in MM.1S cells^[1].
TO-1187 (100 nM, 6 h) only degrades HDAC6 in MM.1S cells without affecting other proteins (such as CRBN novel substrates: IKZF1, IKZF3, CK1α, SALL4 and GSPT1), further confirming its high selectivity^[1].
In Vivo:TO-1187 (5 mg/kg, i.v. one dose) significantly reduces HDAC6 protein levels in the liver in a C57BL/6J mice model, indicating that it has good in vivo degradation activity^[1].