Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates

被引：40

作者：

Braggio, Simone ^{[1
]}

Montanari, Dino ^{[1
]}

Rossi, Tino ^{[2
]}

Ratti, Emiliangelo

机构：

[1] GlaxoSmithKline R&D, Neurosci Ctr Excellence Drug Discovery, Discovery DMPK, I-37135 Verona, Italy

[2] GlaxoSmithKline R&D, Neurosci Ctr Excellence Drug Discovery, Preclin DD & Enabling Tech, I-37135 Verona, Italy

来源：

EXPERT OPINION ON DRUG DISCOVERY | 2010年 / 5卷 / 07期

关键词：

ADMET; biophase; CNS; developability; drug discovery; ligand efficiency; pharmacodynamics; pharmacokinetics; physicochemical properties; volume of distribution; DISCOVERY;

D O I：

10.1517/17460441.2010.490553

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

As a result of their wide acceptance and conceptual simplicity, drug-like concepts are having a major influence on the drug discovery process, particularly in the selection of the 'optimal' absorption, distribution, metabolism, excretion and toxicity and physicochemical parameters space. While they have an undisputable value when assessing the potential of lead series or in evaluating inherent risk of a portfolio of drug candidates, they result much less useful in weighing up compounds for the selection of the best potential clinical candidate. We introduce the concept of drug efficiency as a new tool both to guide the drug discovery program teams during the lead optimization phase and to better assess the developability potential of a drug candidate.

引用

页码：609 / 618

页数：10

共 20 条

[1] Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors:: Identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist [J].