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 capable of penetrating the blood-brain barrier and demonstrates favorable pharmacokinetic properties in tumor-bearing nude mice at a dosage of 30 mg/kg orally. At 80 mg/kg orally, it significantly reduces symptoms of psoriasis by day 11 and lessens epidermal thickness in a psoriasis xenograft transplantation model [2]. Furthermore, a dose of 160 mg/kg orally leads to the degradation of HSP90 client proteins, inhibiting tumor growth and extending survival in various U87MG glioblastoma animal models. This dosage also enhances antitumor effects in an erlotinib-resistant H1975 subcutaneous tumor model. Dose-dependent suppression of tumor growth in the U87MG subcutaneous (s.c.) tumor model is observed with oral doses of 40, 80, or 160 mg/kg administered every other day (q2d) [1]. Additionally, oral doses of 80, 120, and 160 mg/kg exhibit a dose-dependent reduction of tumor growth in the H1975 subcutaneous tumor model [3].