2. Academic Validation
  3. The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity

The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity

  • ACS Med Chem Lett. 2012 Mar 26;3(5):352-6. doi: 10.1021/ml200284s.
Mark J Robertson 1,  Gordana Hadzic 1,  Joseph Ambrus 1,  D Yuri Pomè 1,  Emily Hyde 1,  Ainslie Whiting 2,  Anna Mariana 2,  Lisa von Kleist 3,  Ngoc Chau 2,  Volker Haucke 3,  Phillip J Robinson 2,  Adam McCluskey 1
Affiliations

Affiliations

  • 1 Chemistry, The University of Newcastle , University Drive, Callaghan, NSW 2308, Australia.
  • 2 Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney , Sydney, NSW 2145, Australia.
  • 3 Leibniz Institut für Molekulare Pharmakologie & Freie Universität Berlin , 13125 Berlin, Germany.
PMID: 24900478 DOI: 10.1021/ml200284s
Abstract

Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential Dynamin I GTPase inhibitors. Twenty-six were more potent than the lead compound with 13 returning IC50 values ≤10 μM, making the Rhodadyn series among the most active Dynamin inhibitors reported. Two analogues were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with IC50(RME) = 7.0 ± 2.2 and 5.9 ± 1.0 μM, respectively. These compounds are equipotent with the best reported in-cell Dynamin inhibitors.

Keywords

Knoevengal condensation; dynamin inhibition; rhodanine.

Figures
Products