HDAC6/HSP90-IN-2 (compound 6e) is a dual inhibitor of HDAC6 and Hsp90 with IC50 values of 105.7 nM and 61 nM, respectively, primarily used in cancer research [1].

HDAC6:106 nM, HDAC7:1691 nM, HDAC3:1539 nM, HDAC1:654.5 nM

HDAC6/HSP90-IN-2 (compound 6e), in concentrations from 0.05 to 2 μM over 24 hours, dose-dependently affects HSP90, HDAC6, and Hsp90-regulated signaling pathways, promoting HSP90 acetylation at 2 μM. It inhibits H1975 non-small cell lung cancer cell growth (0-100 μM, 24-72 hours) and induces apoptosis (0-2 μM, 24 hours). Western blot analyses show dose-dependent inhibition of Hsp90 and HDACs, increased Hsp70 and Hsp90 expression likely via HSF1 activation (0.05, 0.1, 0.5, 1, 2 μM, 24 hours), and enhanced Hsp90 K294 acetylation at 2 μM. Apoptosis assays reveal dose-dependent early and late apoptosis in H1975 cells (0, 0.5, 1, 2 μM, 24 hours). Cell viability assays indicate a GI50 value of 1.7 μM.

HDAC6/HSP90-IN-2 (compound 6e), administered at a dosage of 25-50 mg/kg via intraperitoneal injection on weekdays for six weeks, demonstrated significant antitumor activity in NOD-scid IL2Rgammanull (NSG) mice xenografted with H1975 cells. The treatment not only delayed tumor growth after two weeks but also effectively reduced tumor growth rates in the mice [1].