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.
Morphy
Richard
R
Medicinal Chemistry Department, Organon Laboratories, Newhouse, Lanarkshire ML1 5SH, UK. r.morphy@organon.co.uk
Kay
Corinne
C
Rankovic
Zoran
Z
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