Expanding Bioactive Fragment Space with the Generated Database GDB-13s.

Buehler, Ye; Reymond, Jean-Louis (2023). Expanding Bioactive Fragment Space with the Generated Database GDB-13s. Journal of chemical information and modeling, 63(20), pp. 6239-6248. American Chemical Society 10.1021/acs.jcim.3c01096

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Identifying innovative fragments for drug design can help medicinal chemistry address new targets and overcome the limitations of the classical molecular series. By deconstructing molecules into ring fragments (RFs, consisting of ring atoms plus ring-adjacent atoms) and acyclic fragments (AFs, consisting of only acyclic atoms), we find that public databases of molecules (i.e., ZINC and PubChem) and natural products (i.e., COCONUT) contain mostly RFs and AFs of up to 13 atoms. We also find that many RFs and AFs are enriched in bioactive vs inactive compounds from ChEMBL. We then analyze the generated database GDB-13s, which enumerates 99 million possible molecules of up to 13 atoms, for RFs and AFs resembling ChEMBL bioactive RFs and AFs. This analysis reveals a large number of novel RFs and AFs that are structurally simple, have favorable synthetic accessibility scores, and represent opportunities for synthetic chemistry to contribute to drug innovation in the context of fragment-based drug discovery.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Buehler, Ye, Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

ISSN:

1549-9596

Publisher:

American Chemical Society

Language:

English

Submitter:

Pubmed Import

Date Deposited:

19 Sep 2023 09:20

Last Modified:

24 Oct 2023 00:15

Publisher DOI:

10.1021/acs.jcim.3c01096

PubMed ID:

37722101

BORIS DOI:

10.48350/186386

URI:

https://boris.unibe.ch/id/eprint/186386

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