A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

Abstract

Drug repurposing is a strategy consisting of finding new indications for already known marketed drugs used in various clinical settings or highly characterized compounds despite they can be failed drugs. Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. The success rate of drugs repurposing approach accounts for approximately 30% of new FDA approved drugs and vaccines in recent years.This review focuses on the status of drugs repurposing approach for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases.Efforts have been made to provide structural features and mode of actions of drugs.Keywords: Cancer, drug repositioning, drug reprofiling, recycling of drugs, drug discovery, inflammation, neurodegenerative diseases, skin diseases. since clinical and pre-clinical studies of the re-purposed candidates are already being documented in the original indication(s). Thus, it reduces the time and cost needed to reach the market and risk intrinsic to any research and development program. Moreover, the risk of clinical failure is also low. As an added advantage, this approach gives a possibility to widen the market and to prolong the application of the patent life of a drug. There are mainly two ways to proceed drug-repositioning approach such as experimental strategies and computational strategies.Experimental repurposing strategies include binding assays and phenotypic screening methods, which can be to find binding interactions of drug molecules to assay components and to identify lead compounds from a vide range of compound libraries, respectively [10].Computational approaches are categorized into target-/mechanism based, knowledge-based, pathway-and network-based approaches. These approaches are proven economic in discovering novel therapeutic ligands. Most notably, computational methods augment the drug discovery process by effectively utilizing cheminformatics, bioinformatics, network biology and systems biology. More specifically, these methods exploit known targets, drugs, disease biomarkers or pathways to establish novel methods and accelerate the planning of crucial clinical trials [11].In this perspective, we focused on the status of drugs repurposing approaches for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases. Efforts have been made to provide structural features, and modes of action of drugs, which are exclusively small molecules, peptidomimetics, and macrocyclic compounds.Antibodies, vaccines, and any other biological drugs are not discussed. Drugs repositioning for skin whitening activity.Melanin is a collection of natural pigments that primarily determine the skin, hair and hair color of the human. Melanocytes, which are found in the basal layer of the epidermis, produce melanin by the process called melanogenesis upon the skin exposure to the ultra...

Ofloxacin as a Disruptor of Actin Aggresome “Hirano Bodies”: A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases

“…Drug repositioning is a new approach that has been emerging recently for the treatment of various diseases as any lead molecule under a de novo drug discovery program, which takes around 10–15 years to come into the market and probably has a success rate of less than 10%. It has been a known fact that the FDA has approved different molecules against 400 human proteins ( Pillaiyar et al, 2020 ). These proteins are classified under the umbrella of enzymes, transporters, G protein-coupled receptors (GPCRs), cluster of differentiation (CD) markers, voltage-gated ion channels, and nuclear receptors ( Pillaiyar et al, 2020 ).…”

“…It has been a known fact that the FDA has approved different molecules against 400 human proteins ( Pillaiyar et al, 2020 ). These proteins are classified under the umbrella of enzymes, transporters, G protein-coupled receptors (GPCRs), cluster of differentiation (CD) markers, voltage-gated ion channels, and nuclear receptors ( Pillaiyar et al, 2020 ). Actin is one of the globular proteins with an ATPase binding cleft and an intrinsic property to polymerize ( Oda et al, 2009 ; McKayed and Simpson, 2013 ).…”

Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic?

“…In the history of drug production and discovery, often a molecule that is characterized with a well-defined function can, with new studies, be employed for a new purpose. This practice is called drug repositioning [10]. In helminthology, some drugs that were not originally used against helminths have shown high efficacy against some worms, such as mefloquine for Echinococcus multilocularis [11].…”

Ketamine can be produced by Pochonia chlamydosporia: an old molecule and a new anthelmintic?

“…In the history of drug production and discovery, often a molecule that is characterized with a well-de ned function can, with new studies, be employed for a new purpose. This practice is called drug repositioning [10]. In helminthology, some drugs that were not originally used against helminths have shown high e cacy against some worms, such as me oquine for Echinococcus multilocularis [11].…”