From magic bullets to designed multiple ligands.
Increasingly, it is being recognised that a balanced modulation of several targets can provide a superior therapeutic effect and side effect profile compared to the action of a selective ligand. Rational approaches in which structural features from selective ligands are combined have produced designed multiple ligands that span a wide variety of targets and target classes. A key challenge in the design of multiple ligands is attaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. An analysis of literature examples reveals trends and insights that might help medicinal chemists discover the next generation of these types of compounds.
Medicinal Chemistry Department, Organon Laboratories, Newhouse, Lanarkshire ML1 5SH, UK. r.morphy@organon.co.uk
Richard
R
Morphy
Corinne
C
Kay
Zoran
Z
Rankovic
D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D004359:Drug Therapy, Combination; D006801:Humans; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D004364:Pharmaceutical Preparations