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Spatially constrained hyperpolarized 13C MRI pharmacokinetic rate constant map estimation using a digital brain phantom and a U-Net.
J Magn Reson
January 2025
UC Berkeley - UCSF Graduate Program in Bioengineering, 1700 4th St, San Francisco, CA 94158, USA; Radiology and Biomedical Imaging, University of California, San Francisco, 1700 4th St, San Francisco, CA 94158, USA.
Fitting rate constants to Hyperpolarized [1-C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting.
View Article and Find Full Text PDFDelineating CYP2C19-Mediated Interactions: Network Pharmacology Investigation of Ilaprazole and Clopidogrel versus Conventional Proton Pump Inhibitors.
Curr Drug Discov Technol
December 2024
Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District, Tamilnadu, 603203, India.
Background: Clopidogrel, an antiplatelet drug commonly used in cardiovascular disease, is metabolized by the liver mainly through CYP2C19. Concomitant use of Proton pump inhibitors along with clopidogrel may affect the potency of clopidogrel by CYP2C19 inhibition. However, a novel PPI, ilaprazole is known to differ in its pharmacokinetic features, given the potential differences between ilaprazole's interactions and their metabolism with clopidogrel.
View Article and Find Full Text PDFPhytosome-Enhanced Secondary Metabolites for Improved Anticancer Efficacy: Mechanisms and Bioavailability Review.
Drug Des Devel Ther
January 2025
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia.
Purpose: Phytosome technology, an advanced lipid-based delivery system, offers a promising solution for enhancing the bioavailability and therapeutic efficacy of secondary metabolites, particularly in cancer treatment. These metabolites, such as flavonoids, terpenoids, and alkaloids, possess significant anticancer potential but are often limited by poor solubility and low absorption. This review aims to investigate how phytosome encapsulation improves the pharmacokinetic profiles and anticancer effectiveness of these bioactive compounds.
View Article and Find Full Text PDFDetailed Structural Elucidation of Antibody-Drug Conjugate Biotransformation Species Using High Resolution Multiple Reaction Monitoring Mass Spectrometry with Orthogonal Dissociation Methods.
ACS Pharmacol Transl Sci
January 2025
Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 121 Oyster Point Blvd, South San Francisco, California 94080, United States.
Antibody-drug conjugates (ADCs) are a promising drug modality substantially expanding in both the discovery space and clinical development. Assessing the biotransformation of ADCs and is important in understanding their stability and pharmacokinetic properties. We previously reported biotransformation pathways for the anti-B7H4 topoisomerase I inhibitor ADC, AZD8205, puxitatug samrotecan, that underpin its structural stability using an intact protein liquid chromatography-high resolution mass spectrometry (LC-HRMS) approach.
View Article and Find Full Text PDFA novel ROR1-targeting antibody-PROTAC conjugate promotes BRD4 degradation for solid tumor treatment.
Theranostics
January 2025
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Proteolysis Targeting Chimeras (PROTACs) are bifunctional compounds that have been extensively studied for their role in targeted protein degradation (TPD). The capacity to degrade validated or undruggable targets provides PROTACs with significant potency in cancer therapy. However, the clinical application of PROTACs is limited by their poor potency and unfavorable pharmacokinetic properties.
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