Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Despite the established exposure-pharmacodynamic relationships for many TKIs, the mechanisms underlying the agents' unpredictable pharmacokinetic profiles remain poorly understood. We report here that the disposition of many TKIs depends on hepatic transport by OATP1B1, a process that has toxicologic ramifications for agents that are associated with hepatotoxicity.
Authors
- Mahesh R. Nepal (ORCID: https://orcid.org/0000-0001-7259-2699)
- Kevin M. Huang (ORCID: https://orcid.org/0000-0001-6561-3295)
- Thomas Drabison
- Xiaolin Cheng (ORCID: https://orcid.org/0000-0002-7396-3225)
- Peter de Bruijn (ORCID: https://orcid.org/0000-0003-3372-5756)
- Navjotsingh Pabla (ORCID: https://orcid.org/0000-0001-9408-0539)
- Alex Sparreboom (ORCID: https://orcid.org/0000-0003-2660-6644)
- Josie A. Silvaroli (ORCID: https://orcid.org/0000-0002-4505-3670)
- Eric D. Eisenmann (ORCID: https://orcid.org/0000-0003-1176-675X)
- Ron H.J. Mathijssen (ORCID: https://orcid.org/0000-0001-5667-5697)
- Sharyn D. Baker (ORCID: https://orcid.org/0000-0003-3062-3252)
- Shuiying Hu (ORCID: https://orcid.org/0000-0002-9806-7734)
- Mike Boeckman
- Zahra Talebi (ORCID: https://orcid.org/0000-0001-9166-5160)
- Yan Yang (ORCID: https://orcid.org/0000-0001-5608-5785)
- Anika T. Chowdhury
Institutions
- Erasmus MC (NL)
- Erasmus MC Cancer Institute (NL)
- The Ohio State University (US)
Publication Details
- Journal
- Cancer Research Communications
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1158/2767-9764.crc-24-0332
- Citations
- 6
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 1.70
Funders
- Eli Lilly and Company
- Ohio State University
- Pelotonia
- National Institutes of Health