Recent advances in physicochemical and ADMET profiling in drug discovery.
The drastic increase in the cost for discovering and developing a new drug along with the high attrition rate of development candidates led to shifting drug-discovery strategy to parallel assessment of comprehensive drug physicochemical, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties alongside efficacy. With the proposal of a profiling paradigm and utilization of integrated risk assessment, one can exponentially enhance the predictive power of in vitro tools by taking into consideration the interplay among profiling parameters. In particular, this article will review recent advances in accurate assessment of solubility and other physicochemical parameters. The proper interpretation of these experimental data is crucial for rapid and meaningful risk assessment and rational optimization of drug candidates in drug discovery. The impact of these tools on assisting drug-discovery teams in establishing in vitro-in vivo correlation (IVIVC) as well as structure-property relationship (SPR) will be presented.
Wang
Jianling
J
ADME Profiling Cambridge, Metabolism and Pharmacokinetics, Novartis Institute for Biomedical Research, 250 Mass Ave, Cambridge, MA 02139, USA. jianling.wang@novartis.com
Skolnik
Suzanne
S
D000042:Absorption; D000818:Animals; D001711:Biotransformation; D002627:Chemistry, Physical / Q000379:methods*; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D012995:Solubility; D013816:Thermodynamics; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations