Related Experiment Video
Updated: Apr 8, 2026

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
Published on: January 11, 2017
1,8-Naphthalimide derivatives: new leads against dynamin I GTPase activity
Mohammed K Abdel-Hamid1, Kylie A Macgregor, Luke R Odell
1Centre for Chemical Biology, Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia. Adam.McCluskey@newcastle.edu.au.
Abstract:
Fragment-based in silico screening against dynamin I (dynI) GTPase activity identified the 1,8-naphthalimide framework as a potential scaffold for the design of new inhibitors targeting the GTP binding pocket of dynI. Structure-based design, synthesis and subsequent optimization resulted in the development of a library of 1,8-naphthalimide derivatives, called the Naphthaladyn™ series, with compounds 23 and 29 being the most active (IC50 of 19.1 ± 0.3 and 18.5 ± 1.7 μM respectively). Compound 29 showed effective inhibition of clathrin-mediated endocytosis (IC50(CME) 66 μM). The results introduce 29 as an optimised GTP-competitive lead Naphthaladyn™ compound for the further development of naphthalimide-based dynI GTPase inhibitors.
Related Concept Videos
Pinching-off of Coated Vesicles
GTPases and their Regulation
Large G-proteins,...
GTPases and their Regulation
Actin Filament Depolymerization
In F-actin, the ADF/cofilin proteins...
Destabilization of Microtubules
Rab Proteins
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...

