Bhutani, PriyadeepJoshi, GauravRaja, NivethithaBachhav, NamrataRajanna, Prabhakar K.Bhutani, HemantPaul, Atish T.Kumar, Raj2024-01-212024-08-132024-01-212024-08-132021-02-2222262310.1021/acs.jmedchem.0c01786https://kr.cup.edu.in/handle/32116/3514In the present work, we report compilation and analysis of 245 drugs, including small and macromolecules approved by the U.S. FDA from 2015 until June 2020. Nearly 29% of the drugs were approved for the treatment of various types of cancers. Other major therapeutic areas of focus were infectious diseases (14%); neurological conditions (12%); and genetic, metabolic, and cardiovascular disorders (7-8% each). Itemization of the approved drugs according to the year of approval, sponsor, target, chemical class, major drug-metabolizing enzyme(s), route of administration/elimination, and drug-drug interaction liability (perpetrator or/and victim) is presented and discussed. An effort has been made to analyze the pharmacophores to identify the structural (e.g., aromatic, heterocycle, and aliphatic), elemental (e.g., boron, sulfur, fluorine, phosphorus, and deuterium), and functional group (e.g., nitro drugs) diversity among the approved drugs. Further, descriptor-based chemical space analysis of FDA approved drugs and several strategies utilized for optimizing metabolism leading to their discoveries have been emphasized. Finally, an analysis of drug-likeness for the approved drugs is presented. � 2021 American Chemical Society.en-USDrug ApprovalHumansOrganic ChemicalsUnited StatesUnited States Food and Drug Administrationagents acting on the genital systemagents acting on the peripheral nervous and neuromuscular systemsagents affecting metabolismantibody drug conjugateantiinfective agentantineoplastic agentbiologic factors and agents acting on the immune systemboroncardiovascular agentcentral nervous system agentsdermatological agentdeuteriumdiagnostic agentdrug metabolizing enzymefluorinefunctional groupgastrointestinal agentmiscellaneous drugs and agentsnutrition supplementphosphorusrespiratory tract agentsulfurorganic compoundautoimmune diseasecardiovascular diseasedrug approvaldrug indicationdrug interactiondrug metabolismdrug structureFood and Drug Administrationgastrointestinal diseasegenetic disorderinfectionmacromoleculemalignant neoplasmmetabolic disorderneurologic diseaseophthalmologypharmacophorerespiratory tract diseaseReviewUnited StateschemistryhumanReviewhttps://pubs.acs.org/doi/10.1021/acs.jmedchem.0c01786