17β-Hydroxysteroid Dehydrogenase Type 1 Inhibition: A Potential Treatment Option for Non-Small Cell Lung Cancer.
Gargano EM, Mohamed A, Abdelsamie AS, Mangiatordi GF, Drzewiecka H, Jagodziński PP, Mazzini A, van Koppen CJ, Laschke MW, Nicolotti O, Carotti A, Marchais-Oberwinkler S, Hartmann RW, Frotscher M.
In the face of the clinical challenge posed by non-small cell lung cancer (NSCLC), the present need for new therapeutic approaches is genuine. Up to now, no proof existed that 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a viable target for treating this disease. Synthesis of a rationally designed library of 2,5-disubstituted furan derivatives followed by biological screening led to the discovery of 17β-HSD1 inhibitor <b>1</b>, capable of fully inhibiting human NSCLC Calu-1 cell proliferation. Its pharmacological profile renders it eligible for further <i>in vivo</i> studies. The very high selectivity of <b>1</b> over 17β-HSD2 was investigated, revealing a rational approach for the design of selective inhibitors. 17β-HSD1 and <b>1</b> hold promise in fighting NSCLC.