2. Academic Validation
  3. Hybrid dual aromatase-steroid sulfatase inhibitors with exquisite picomolar inhibitory activity

Hybrid dual aromatase-steroid sulfatase inhibitors with exquisite picomolar inhibitory activity

  • ACS Med Chem Lett. 2010 Dec 29;2(3):243-7. doi: 10.1021/ml100273k.
L W Lawrence Woo 1,  Christian Bubert 1,  Atul Purohit 2,  Barry V L Potter 1
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath , Claverton Down, Bath BA2 7AY, United Kingdom.
  • 2 Endocrinology and Metabolic Medicine, Imperial College London, Faculty of Medicine, St. Mary's Hospital , London W2 1NY, United Kingdom.
PMID: 24900302 DOI: 10.1021/ml100273k
Abstract

Single agents against multiple drug targets are highly topical. Hormone-dependent breast Cancer (HDBC) may be more effectively treated by dual inhibition of aromatase and Steroid Sulfatase (STS), and several dual aromatase-sulfatase inhibitors (DASIs) have been recently reported. The best compounds from two leading classes of DASI, 3 and 9, are low nanomolar inhibitors. In search of a novel class of DASI, core motifs of two leading classes were combined to give a series of hybrid structures, with several compounds showing markedly improved dual inhibitory activities in the picomolar range in JEG-3 cells. Thus, DASIs 14 (IC50: aromatase, 15 pM; STS, 830 pM) and 15 (IC50: aromatase, 18 pM; STS, 130 pM) are the first examples of an exceptional new class of highly potent dual inhibitor that should encourage further development toward multitargeted therapeutic intervention in HDBC.

Keywords

Hybrid; aromatase; cancer; dual inhibitors; sulfatase.

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