Debio 0932 (CUDC-305) is a heat shock protein 90 (Hsp90) inhibitor that targets the n-terminal atp-binding pocket to promote apoptosis, and has the advantage of being orally available and able to cross the blood-brain barrier (BBB) for the treatment of cancers such as non-small-cell lung cancer (NSCLC) and neuroblastoma.

MDA-MB-231 cells:10.66 µm, H1299 cells:20.33±5.39 µM, MCF-7 cells:6.19 µM, A549 cells:3.26±2.82 µM, HSP90 α:100 nM, HSP90 β:103 nM

Debio 0932 exhibits dose- and time-dependent proliferation inhibition in MCF-7 and MDA-MB-231 cells, with IC50 values of 6.19 µM and 10.66 µM at 48 hours, respectively. It promotes apoptosis by upregulating Bax/Bcl-2, activating Caspase-9, and inhibiting HUVEC migration [1]. In NSCLC, the IC50 values against A549, H1299, and H1975 cells are 3.26±2.82 µM, 20.33±5.39 µM, and 3.16±1.04 µM, respectively. It induces cell cycle arrest and apoptosis, and targets Hsp90 with an IC50 value of 70 nmol/L, leading to the degradation of mutant EGFR and K-RAS, thus reversing erlotinib resistance [2,3].

In a psoriasis xenograft model, treatment with Debio 0932 (80 mg/kg, orally daily) for 3 weeks resulted in a significant clinical improvement by day 11, with a marked reduction in epidermal thickness [4]. In the U87MG glioblastoma mouse model, treatment with Debio 0932 (160 mg/kg, every other day) induced tumor regression. In an acute myeloid leukemia (AML) mouse model, after 3 weeks of treatment with Debio 0932 (160 mg/kg, every other day), complete tumor regression was observed, with good drug safety [5].