Publication

Functionalized pyrrolidine inhibitors of human alpha- mannosidases II in cancer: optimizing the fit to the active site

Sandrine Gerber, Hélène Fiaux
2008
Journal Articles

Abstract

Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi α- mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of α-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.

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https://infoscience.epfl.ch/entities/publication/4442f88d-868a-4703-b35a-28a73d4f3bee

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Sandrine Gerber, Hélène Fiaux
2008
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/4442f88d-868a-4703-b35a-28a73d4f3bee

About this result

Related concepts (27)

Lead compound

A lead compound (ˈliːd, i.e. a "leading" compound, not to be confused with various compounds of the metallic element lead) in drug discovery is a chemical compound that has pharmacological or biological activity likely to be therapeutically useful, but may nevertheless have suboptimal structure that requires modification to fit better to the target; lead drugs offer the prospect of being followed by back-up compounds. Its chemical structure serves as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.

Lead

Lead is a chemical element with the symbol Pb (from the Latin plumbum) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cut, lead is a shiny gray with a hint of blue. It tarnishes to a dull gray color when exposed to air. Lead has the highest atomic number of any stable element and three of its isotopes are endpoints of major nuclear decay chains of heavier elements.

Hit to lead

Hit to lead (H2L) also known as lead generation is a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO).

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