On the discovery of new potent human ...
Document type :
Article dans une revue scientifique
DOI :
PMID :
Permalink :
Title :
On the discovery of new potent human farnesyltransferase inhibitors: emerging pyroglutamic derivatives
Author(s) :
Homerin, Germain [Auteur]
Lipka, Emmanuelle [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Rigo, Benoit [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubois, Joelle [Auteur]
Ghinet, Alina [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lipka, Emmanuelle [Auteur]

Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Rigo, Benoit [Auteur]
Farce, Amaury [Auteur]

Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubois, Joelle [Auteur]
Ghinet, Alina [Auteur]

Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Journal title :
Organic & Biomolecular Chemistry
Abbreviated title :
Org. Biomol. Chem.
Volume number :
15
Pages :
8110-8118
Publication date :
2017-10-14
ISSN :
1477-0520
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford ...
Show more >In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford progeria syndrome), and in delta hepatitis, cardiovascular or neuroinflammatory diseases, we have just discovered a new series of powerful inhibitors. These molecules are pyroglutamic acid derivatives, and were evaluated on human farnesyltransferase in vitro then modeled in silico on the active site of the protein. Three main points of the pyroglutamic acid cycle have undergone chemical modulations pyroglutamides in position 5 (compounds 7a-h), constrained bicyclic analogues of pyrroloimidazoledione type (compounds 1a-h), modulation of the position 3 (compounds 2-5 and 8), and allowed the first SAR in the field. Five derivatives in the current work have IC values in the small nanomolar range (2-5 nM). These new lead compounds open the way for the next generation of farnesyltransferase inhibitors.Show less >
Show more >In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford progeria syndrome), and in delta hepatitis, cardiovascular or neuroinflammatory diseases, we have just discovered a new series of powerful inhibitors. These molecules are pyroglutamic acid derivatives, and were evaluated on human farnesyltransferase in vitro then modeled in silico on the active site of the protein. Three main points of the pyroglutamic acid cycle have undergone chemical modulations pyroglutamides in position 5 (compounds 7a-h), constrained bicyclic analogues of pyrroloimidazoledione type (compounds 1a-h), modulation of the position 3 (compounds 2-5 and 8), and allowed the first SAR in the field. Five derivatives in the current work have IC values in the small nanomolar range (2-5 nM). These new lead compounds open the way for the next generation of farnesyltransferase inhibitors.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:08:44Z