Debio 0932 is an orally active inhibitor of HSP90 (IC50s: 100 and 103 nM for HSP90α and HSP90β, respectively).

HSP90 α:100 nM, HSP90 β:103 nM

Debio 0932 also displays inhibitory activities against the proliferation of 40 cancer cell lines (containing 34 solid and 6 hematologic tumor-derived lines) (IC50 ranging from 40 to 900 nM) (mean IC50, 220 nM) [1]. Debio 0932 binds to the tumor HSP90 complex( a mean IC50: 48.8 nM). Debio 0932 (1 μM) promotes degradation of multiple HSP90 client proteins in cancer cell lines. Debio 0932 potently binds to cancer-derived HSP90 complex (IC50: 61.2 nM in H1975 cells and 74.2 nM in H1993 cells, respectively). Debio 0932 (CUDC-305, 1 μM) durably induces oncoprotein degradation in NSCLC cell lines with mutations that can confer resistance to erlotinib [3].

Debio 0932 is able to cross the blood-brain barrier. Debio 0932 (30 mg/kg, p.o.) exhibits favorable pharmacokinetic profiles in tumor-bearing nude mice. Debio 0932 (80 mg/kg, p.o.) significantly alleviates psoriasis by day 11 and decreases epidermal thickness in psoriasis xenograft transplantation model [2]. Debio 0932 (160 mg/kg, p.o.) causes degradation of HSP90 client proteins, suppresses tumor growth, and also prolongs survival in various animal models of U87MG glioblastoma. Debio 0932 (160 mg/kg, p.o.) also promotes antitumor activity in the erlotinib-resistant H1975 subcutaneous tumor model. Debio 0932 (40, 80, or 160 mg/kg, p.o.) also dose-dependently inhibits tumor growth in the U87MG s.c. tumor model by every-other-day (q2d) dosing [1]. Debio 0932 (80, 120, and 160 mg/kg, p.o.) displays dose-dependent inhibition of tumor growth in the H1975 subcutaneous tumor model [3].