17β-Hydroxysteroid Dehydrogenase Type 1 Inhibition: A Potential Treatment Option for Non-Small Cell Lung Cancer

  • ACS Med Chem Lett. 2021 Nov 18;12(12):1920-1924. doi: 10.1021/acsmedchemlett.1c00462.
Emanuele M Gargano  1 ,  Abdelrahman Mohamed  1  2 ,  Ahmed S Abdelsamie  3  4 ,  Giuseppe F Mangiatordi  5 ,  Hanna Drzewiecka  6 ,  Paweł P Jagodziński  6 ,  Arcangela Mazzini  1 ,  Chris J van Koppen  7 ,  Matthias W Laschke  8 ,  Orazio Nicolotti  5 ,  Angelo Carotti  5 ,  Sandrine Marchais-Oberwinkler  1 ,  Rolf W Hartmann  1  3 ,  Martin Frotscher  1
Affiliations
  • 1. Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123 Saarbrücken, Germany.
  • 2. Pharmaceutical Organic Chemistry Department, Assiut University, Assiut 71526, Egypt.
  • 3. Department of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E81, D-66123 Saarbrücken, Germany.
  • 4. Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki, Cairo 12311, Egypt.
  • 5. Dipartimento di Farmacia Scienze del Farmaco, Università degli Studi di Bari, V. Orabona 4, I-70125 Bari, Italy.
  • 6. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Świȩcickiego 6 Street, 60-781 Poznan, Poland.
  • 7. ElexoPharm GmbH, Campus A12, D-66123 Saarbrücken, Germany.
  • 8. Institute for Clinical and Experimental Surgery, Saarland University, D-66421, Homburg, Saar, Germany.
PMID: 34917255 DOI: 10.1021/acsmedchemlett.1c00462
Abstract

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 1, capable of fully inhibiting human NSCLC Calu-1 cell proliferation. Its pharmacological profile renders it eligible for further in vivo studies. The very high selectivity of 1 over 17β-HSD2 was investigated, revealing a rational approach for the design of selective inhibitors. 17β-HSD1 and 1 hold promise in fighting NSCLC.

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