PXD057282-1

PXD057282 is an original dataset announced via ProteomeXchange.

Title	Impact of Variation in CYP3A and CYP2C8 on Tucatinib Metabolic Clearance in Human Liver Microsomes
Description	Tucatinib is a tyrosine kinase inhibitor (TKI) indicated for HER2 positive breast cancer. It is metabolized primarily by cytochrome P450 (CYP) 2C8 and CYP3A. Given the interindividual variability in the pharmacokinetics of some TKIs, this study explored how variability in CYP2C8 and CYP3A activities and concentrations can influence variability in overall tucatinib metabolic clearance. Tucatinib depletion, CYP activities, and CYP concentrations were measured in human liver microsomes from 21 donors (males n = 11, females n = 10). Specifically, CYP2C8, CYP3A4, and CYP3A5 protein concentrations were measured using quantitative targeted absolute proteomics (QTAP), and the raw data for this, including peak area data, are deposited here. Tucatinib clearance was significantly correlated with both CYP2C8 and CYP3A enzyme activities and protein concentrations in the donor cohort. A multiple linear regression model was developed to determine the most significant parameters influencing tucatinib clearance. The model including only CYP2C8 and CYP3A activities provided the best fit, indicating a strong predictive ability. Overall, CYP3A activity was the most significant predictor of tucatinib clearance in the human liver microsomal samples tested.
HostingRepository	PRIDE
AnnounceDate	2025-04-17
AnnouncementXML	Submission_2025-04-16_19:21:22.515.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Fallon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q TRAP

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-29 04:59:22	ID requested
⏵ 1	2025-04-16 19:21:22	announced

10.1016/J.DMD.2025.100061;

submitter keyword: Quantitative Proteomics, M-Class Acquity, kinase inhibitor, triple quadrupole 7500

Klarissa Jackson
contact affiliation	Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA
contact email	klarissa.jackson@unc.edu
lab head
John Fallon
contact affiliation	Eshelman School of Pharmacy, University of North Carolina at Chapel Hill
contact email	jfallon@email.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD057282

PRIDE project URI

• PRIDE
  1. PXD057282
     1. Label: PRIDE project
     2. Name: Impact of Variation in CYP3A and CYP2C8 on Tucatinib Metabolic Clearance in Human Liver Microsomes