Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis
Michael G. Thomas, Stephen Brand, Manu De Rycker, Fabio Zuccotto, Iva Lukač, Peter G. Dodd, Eun Jung Ko, Sujatha Manthri, Kate McGonagle, Maria Osuna‐Cabello, Jennifer Riley, Caterina Pont, Frederick R. C. Simeons, Laste Stojanovski, John Thomas, Stephen Thompson, Elisabet Viayna, José M. Fiandor, Julio Martín, Paul G. Wyatt, Timothy J. Miles, Kevin D. Read, María Marco, Ian H. Gilbert
Abstract
profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.
Topics & Concepts
ChemistryScaffoldProteasomeVisceral leishmaniasisPharmacologyLeishmaniasisBiochemistryImmunologyBiologyMedicineBiomedical engineeringResearch on Leishmaniasis StudiesTrypanosoma species research and implicationsBiochemical and Molecular Research