Expanding the Repertoire for "Large Small Molecules": Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
22
01
2021
revised:
15
02
2021
accepted:
15
03
2021
pubmed:
1
4
2021
medline:
27
1
2022
entrez:
31
3
2021
Statut:
ppublish
Résumé
Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (
Identifiants
pubmed: 33785651
pii: 1535-7163.MCT-21-0077
doi: 10.1158/1535-7163.MCT-21-0077
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Prodrugs
0
Sulfonamides
0
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
999-1008Informations de copyright
©2021 American Association for Cancer Research.
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