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

Debio 0932 is an orally active HSP90 inhibitor, with IC50s of 100 and 103 nM for HSP90α and HSP90β, respectively. Debio 0932 (CUDC-305) binds to the tumor HSP90 complex with a mean IC50 of 48.8 nM. Debio 0932 (1 uM) promotes degradation of multiple HSP90 client proteins in cancer cell lines. Debio 0932 also shows inhibitory activities against the proliferation of 40 cancer cell lines (containing 34 solid and 6 hematologic tumor-derived lines) with an IC50 ranging from 40 to 900 nM (mean IC50, 220 nM)[1]. Debio 0932 strongly binds to cancer-derived HSP90 complex with an IC50 of 61.2 nM in H1975 cells and 74.2 nM in H1993 cells, respectively. Debio 0932 (CUDC-305, 1 uM) durably induces oncoprotein degradation in NSCLC cell lines with mutations that can confer resistance to erlotinib[3].

Debio 0932 (CUDC-305, 30 mg/kg, p.o.) exhibits favorable pharmacokinetic profiles in tumor-bearing nude mice. 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 (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 mg/kg, p.o.) significantly alleviates psoriasis by day 11 and decreases epidermal thickness in psoriasis xenograft transplantation model[2]. Debio 0932 (CUDC-305) is able to cross the blood-brain barrier. Debio 0932 (80, 120, and 160 mg/kg, p.o.) shows dose-dependent inhibition of tumor growth in the H1975 subcutaneous tumor model. Debio 0932 (160 mg/kg, p.o.) also promotes antitumor activity in the erlotinib-resistant H1975 subcutaneous tumor model[3].

References:

[1]. Bao R, et al. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res. 2009 Jun 15;15(12):4046-57.

[2]. Stenderup K, et al. Debio 0932, a new oral Hsp90 inhibitor, alleviates psoriasis in a xenograft transplantation model. Acta Derm Venereol. 2014 Nov;94(6):672-6.

[3]. Bao R, et al. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol Cancer Ther. 2009 Dec;8(12):3296-306.