Designed Multiple Ligands. An Emerging Drug Discovery Paradigm

Polycyclic Compounds: Ideal Drug Scaffolds for the Design of Multiple Mechanism Drugs?

“…[1][2][3][4] There has already been a move by some companies in the pharmaceutical industry to combine two compounds into one formulation, an expansion of the earlier concept inherent in polypharmacy (i.e., administering two or more drugs as separate medicines). Examples include the combination of a ␤-adrenergic agonist salmeterol with a steroid fluticasone (Advair, GlaxoSmithKline, London, UK) in the treatment of asthma or combining the cholesterol absorption inhibitor ezetimibe (Zetia, Merck & Co., Inc., NJ) with the HMG-CoA reductase enzyme inhibitor simvastatin (Zocor, Merck & Co., Inc.) to render Vytorin (Merck & Co., Inc./Schering-Plough Corporation, NJ).…”

“…5,6 To minimize adverse drug interactions, a drug candidate could be designed as one compound that targets multiple disease mechanisms. These multi-functional ligands may perform better in diseases with complex pathological pathways, in which a one "disease, one drug" 3 paradigm has not been met with success. In addition, some multifunctional drugs may work better at normalizing the pathology than a single targeted compound would.…”

“…3 This trend may have been initiated by a concurrent surge in neurodegenerative disease and cancer literature, which postulates that these complex diseases may need agents that target disease pathways at multiple points. Although none of these designed drugs have reached the market yet, recent literature suggests this approach to be very promising.…”

“…Although none of these designed drugs have reached the market yet, recent literature suggests this approach to be very promising. 3,4 One question for the medicinal chemist becomes "where to start?" In a review by Morphy and Rankovic, 3,4 the authors describe mechanisms of designing multifunctional drugs.…”

“…3,4 One question for the medicinal chemist becomes "where to start?" In a review by Morphy and Rankovic, 3,4 the authors describe mechanisms of designing multifunctional drugs. It is suggested that multifunctional drugs can be designed by starting from a single compound or from two compounds.…”