2. Academic Validation
  3. Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells

Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells

  • Eur J Med Chem. 2020 Oct 1;203:112621. doi: 10.1016/j.ejmech.2020.112621.
Ramatoulie Camara 1,  Deborah Ogbeni 1,  Lisa Gerstmann 1,  Mehrnoosh Ostovar 1,  Ellie Hurer 1,  Mark Scott 1,  Nasir G Mahmoud 2,  Tomasz Radon 2,  Tatjana Crnogorac-Jurcevic 2,  Pryank Patel 1,  Louise S Mackenzie 3,  David Y S Chau 4,  Stewart B Kirton 1,  Sharon Rossiter 5
Affiliations

Affiliations

  • 1 School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK.
  • 2 Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
  • 3 School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK; School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK.
  • 4 School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK; Eastman Dental Institute, University College London, 256 Grays Inn Rd, London, WC1X 8LD, UK.
  • 5 School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK. Electronic address: [email protected].
PMID: 32707527 DOI: 10.1016/j.ejmech.2020.112621
Abstract

S100P, a calcium-binding protein, is known to advance tumor progression and metastasis in pancreatic and several other cancers. Herein is described the in silico identification of a putative binding pocket of S100P to identify, synthesize and evaluate novel small molecules with the potential to selectively bind S100P and inhibit its activation of cell survival and metastatic pathways. The virtual screening of a drug-like database against the S100P model led to the identification of over 100 clusters of diverse scaffolds. A representative test set identified a number of structurally unrelated hits that inhibit S100P-RAGE interaction, measured by ELISA, and reduce in vitro cell invasion selectively in S100P-expressing pancreatic Cancer cells at 10 μM. This study establishes a proof of concept in the potential for rational design of small molecule S100P inhibitors for drug candidate development.

Keywords

Calcium-binding protein; Inhibitor; Metastasis; Pancreatic cancer; S100P; Virtual screen.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-146695
    99.74%, S100P Inhibitor