A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis.
GI locally activating
Janus kinase (JAK) inhibitors
machine learning (ML)
structure-tissue selectivity-activity-relationship (STAR)
ulcerative colitis
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
received:
07
08
2023
revised:
11
10
2023
accepted:
06
11
2023
pubmed:
19
11
2023
medline:
19
11
2023
entrez:
18
11
2023
Statut:
aheadofprint
Résumé
In this study, we integrated machine learning (ML), structure-tissue selectivity-activity-relationship (STAR), and wet lab synthesis/testing to design a gastrointestinal (GI) locally activating JAK inhibitor for ulcerative colitis treatment. The JAK inhibitor achieves site-specific efficacy through high local GI tissue selectivity while minimizing the requirement for JAK isoform specificity to reduce systemic toxicity. We used the ML model (CoGT) to classify whether the designed compounds were inhibitors or noninhibitors. Then we used the regression ML model (MTATFP) to predict their IC
Identifiants
pubmed: 37979913
pii: S0021-9258(23)02495-X
doi: 10.1016/j.jbc.2023.105467
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105467Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The University of Michigan filed a patent for these compounds, where some authors are inventors. All other authors declare that they have no conflicts of interest with the contents of this article.