ArticleScientific reports2025
Pharmacokinetic analysis of selective TRPV2 inhibitor SET2 in rats.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The TRPV2 channel, which regulates calcium transients, has emerged as a potential therapeutic target in various diseases, including cardiovascular injury, neurodegeneration, and cancer. However, the absence of selective inhibitors has limited functional studies. Here, we report the in vivo pharmacokinetic profile of SET2, a selective TRPV2 inhibitor. Wistar rats received a single intraperitoneal dose of 25 mg/kg, and plasma and urine samples were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. SET2 reached a peak plasma concentration of 1428 ± 270 ng/ml (≈ 3.55 ± 0.67 µM) within 2 min, followed by a short mean residence time (70.5 ± 5.7 min). Approximately 4.24% of the administered dose was excreted unchanged in urine over 48 h, with renal clearance of 0.0097 ml/min. SET2 caused no significant changes in heart rate, blood pressure, or ECG parameters during peak levels and up to 2 h post-injection. Routine plasma markers remained stable, although a transient increase in plasma troponin I was observed. Our data suggest that SET2 has high plasma bioavailability, limited tissue distribution, and is rapidly cleared. While acute cardiovascular effects were minimal, the troponin I elevation warrants further safety evaluation in chronic studies.
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