Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.
Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples.
Bionics Innovation Center (Hungary). matyus.peter@pharma.semmelweis-univ.hu.|Department of Organic Chemistry, Semmelweis University, Hőgyes E. u. 7, 1092, Budapest, Hungary. matyus.peter@pharma.semmelweis-univ.hu.
Péter
P
Mátyus
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore. phacllc@nus.edu.sg.
Christina L L
CL
Chai
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism; D014150:Antipsychotic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy; D003024:Clozapine / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015195:Drug Design; D004357:Drug Synergism; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D008024:Ligands; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D014150:Antipsychotic Agents; D015815:Cell Adhesion Molecules; D007189:Indans; D008024:Ligands; D004364:Pharmaceutical Preparations; D043643:Receptor, Muscarinic M1; C031967:rasagiline; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D003024:Clozapine
active metabolites; designed multiple ligands (DMLs); drug design; metabolism-activated multitargeting (MAMUT); synergism