Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

Sonja Visentin; Giuseppe Ermondi; Claudio Medana; Nicoletta Pedemonte; Luis Galietta; Giulia Caron

doi:10.1016/j.ejmech.2012.07.017

Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

Sonja Visentin, Giuseppe Ermondi, Claudio Medana, Nicoletta Pedemonte, Luis Galietta, Giulia Caron

Istituto "Giannina Gaslini"

Research output: Contribution to journal › Article › peer-review

Abstract

The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.

Original language	English
Pages (from-to)	188-194
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	55
DOIs	https://doi.org/10.1016/j.ejmech.2012.07.017
Publication status	Published - Sep 2012

Keywords

3D-QSAR
ADME-Tox
CFTR potentiators
DHP
GRIND
VolSurf+

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Pharmacology

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10.1016/j.ejmech.2012.07.017

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title = "Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators",

abstract = "The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.",

keywords = "3D-QSAR, ADME-Tox, CFTR potentiators, DHP, GRIND, VolSurf+",

author = "Sonja Visentin and Giuseppe Ermondi and Claudio Medana and Nicoletta Pedemonte and Luis Galietta and Giulia Caron",

year = "2012",

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doi = "10.1016/j.ejmech.2012.07.017",

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T1 - Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

AU - Visentin, Sonja

AU - Ermondi, Giuseppe

AU - Medana, Claudio

AU - Pedemonte, Nicoletta

AU - Galietta, Luis

AU - Caron, Giulia

PY - 2012/9

Y1 - 2012/9

N2 - The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.

AB - The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.

KW - 3D-QSAR

KW - ADME-Tox

KW - CFTR potentiators

KW - DHP

KW - GRIND

KW - VolSurf+

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AN - SCOPUS:84865734788

VL - 55

SP - 188

EP - 194

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -

Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

Abstract

Keywords

ASJC Scopus subject areas

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