Version 1
: Received: 9 October 2024 / Approved: 10 October 2024 / Online: 12 October 2024 (07:21:18 CEST)
How to cite:
Gong, X.; Xia, G. Preclinical Pharmacokinetics studies of SPH5030, a Novel, Selective, Potent, and Irreversible HER2 Inhibitor. Preprints2024, 2024100856. https://doi.org/10.20944/preprints202410.0856.v1
Gong, X.; Xia, G. Preclinical Pharmacokinetics studies of SPH5030, a Novel, Selective, Potent, and Irreversible HER2 Inhibitor. Preprints 2024, 2024100856. https://doi.org/10.20944/preprints202410.0856.v1
Gong, X.; Xia, G. Preclinical Pharmacokinetics studies of SPH5030, a Novel, Selective, Potent, and Irreversible HER2 Inhibitor. Preprints2024, 2024100856. https://doi.org/10.20944/preprints202410.0856.v1
APA Style
Gong, X., & Xia, G. (2024). Preclinical Pharmacokinetics studies of SPH5030, a Novel, Selective, Potent, and Irreversible HER2 Inhibitor. Preprints. https://doi.org/10.20944/preprints202410.0856.v1
Chicago/Turabian Style
Gong, X. and Guangxin Xia. 2024 "Preclinical Pharmacokinetics studies of SPH5030, a Novel, Selective, Potent, and Irreversible HER2 Inhibitor" Preprints. https://doi.org/10.20944/preprints202410.0856.v1
Abstract
SPH5030 is developed to improve the selectivity of irreversible HER2 inhibitors, which shows excellent activity and better HER2 selectivity against four common HER2 mutants than neratinib and pyrotinib, and consumed to attenuate the off-target adverse events in patients. To comprehensively evaluate SPH5030, the preclinical pharmacokinetic studies of SPH5030 were systematically completed, including in vivo pharmacokinetic, tissue distribution and excretion in Sprague Dawley rats and Cynomolgus monkeys, as well as in vitro drug-drug interaction assessment and metabolite identification in different species. The results showed low clearance, reasonable bioavailability and widely tissues distributed properties, and mainly excreted in the feces in rats. In vitro studies SPH5030 showed stable metabolism and metabolized mainly by CYP3A4/5 and CYP2C8, with no or weak inhibitory potential on CYP450 enzymes and efflux transporters. In Phase I clinical trials, SPH5030 also showed well tolerated at doses ranging from 50 to 600mg and is expected to have an ideal clinical application prospect in the future.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
