Preclinical Pharmacokinetics, Toxicity and Therapeutic Evaluation of QD502
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This preclinical study evaluates the pharmacokinetics, tolerability, and anticancer efficacy of QD502, a novel quinazolinone-based compound, in rodent models. Pharmacokinetic assessments were performed in male BALB/c mice and Sprague-Dawley rats after oral and intravenous administration. QD502's stability in plasma and simulated gastrointestinal fluids, as well as its potential to inhibit human cytochrome P450 (CYP450) enzymes, was also assessed. Acute (14-day) and chronic (28-day) toxicity studies determined the maximum tolerated dose (MTD) and safety profile. In vitro, QD502 showed potent cytotoxicity across various cancer cell lines with sub-micromolar IC50 values. Pharmacokinetic analysis revealed favorable characteristics, including stability in biological matrices and minimal interaction with major CYP450 isoforms. QD502 was well-tolerated at the tested doses, with no significant adverse effects observed. In a colorectal xenograft model, QD502 delayed tumor growth via both oral and intravenous administration without notable toxicity. These results suggest that QD502 possesses promising pharmacokinetic properties, strong anticancer activity, and limited toxicity, highlighting its potential for future cancer treatments.