Occurrence of "Natural Selection" in Successful Small Molecule Drug Discovery.
J Med Chem
; 67(13): 11226-11241, 2024 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-38949112
ABSTRACT
Published compounds from ChEMBL version 32 are used to seek evidence for the occurrence of "natural selection" in drug discovery. Three measures of natural product (NP) character were applied, to compare time- and target-matched compounds reaching the clinic (clinical compounds in phase 1-3 development and approved drugs) with background compounds (reference compounds). Pseudo-NPs (PNPs), containing NP fragments combined in ways inaccessible by nature, are increasing over time, reaching 67% of clinical compounds first disclosed since 2010. PNPs are 54% more likely to be found in post-2008 clinical versus reference compounds. The majority of target classes show increased clinical compound NP character versus their reference compounds. Only 176 NP fragments appear in >1000 clinical compounds published since 2008, yet these make up on average 63% of the clinical compound's core scaffolds. There is untapped potential awaiting exploitation, by applying nature's building blocksâ"natural intelligence"âto drug design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Bibliotecas de Moléculas Pequenas
/
Descoberta de Drogas
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2024
Tipo de documento:
Article