Forward or Backward: Lessons Learned from Small Molecule Drugs Approved by FDA from 2012 to 2022

Mingxiao Gu; Sudan Sun; Qidong You; Lei Wang

doi:10.3390/molecules28247941

Forward or Backward: Lessons Learned from Small Molecule Drugs Approved by FDA from 2012 to 2022

Molecules. 2023 Dec 5;28(24):7941. doi: 10.3390/molecules28247941.

Authors

Mingxiao Gu^{1

2}, Sudan Sun^{1

2}, Qidong You^{1

2}, Lei Wang^{1

2}

Affiliations

¹ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
² Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Abstract

At every juncture in history, the design and identification of new drugs pose significant challenges. To gain valuable insights for future drug development, we conducted a detailed analysis of New Molecular Entitiy (NME) approved by the Food and Drug Administration (FDA) from 2012 to 2022 and focused on the analysis of first-in-class (FIC) small-molecules from a perspective of a medicinal chemist. We compared the change of numbers between all the FDA-approved NMEs and FIC, which could be more visual to analyze the changing trend of FIC. To get a more visual change of molecular physical properties, we computed the annual average trends in molecular weight for FIC across various therapeutic fields. Furthermore, we consolidated essential information into three comprehensive databases, which covered the indications, canonical SMILES, structural formula, research and development (R&D) institutions, molecular weight, calculated LogP (CLogP), and route of administration on all the small-molecule pharmaceutical. Through the analysis of the database of 11 years of approvals, we forecast the development trend of NME approval in the future.

Keywords: first-in-class; new molecular entity; physical and chemical properties; small-molecule drugs.

Publication types

Review

MeSH terms

Databases, Factual
Drug Approval*
Drug Development*
Pharmaceutical Preparations
United States
United States Food and Drug Administration

Substances

Pharmaceutical Preparations

Grants and funding

This study was supported by projects 82173741, 82003582 and 81930100 of the National Natural Science Foundation of China; Project Program of State Key Laboratory of Natural Medicines (China Pharmaceutical University) No. SKLNMZZ2022; Young Elite Scientists Sponsorship Program by CAST (2021QNRC001). National Innovation and Entrepreneurship Training Program for Undergraduate (No. 202310316002Z).