Pharmacokinetics, tissue distribution, and antitumor activity of a novel compound, NY-2, in non-small cell lung cancer

• DOI: 10.3389/fphar.2022.1074576
• Publication Date: 2023-01-16T04:40:26Z
• Authors: Yingshi Zhang; Chang Xu; Xiangbo Xu; Lingxiang Ma; Ruolan Li; Zihua Xu; Qingchun Zhao
• Keywords: Nephrotoxicity

Introduction: ZLDI-8, which has a relatively strong antitumor activity, is an inhibitor of ADAM-17 and acts on the Notch signaling pathway. To further optimize its structure improve series derivatives ZLDI-8 was synthesized. NY-2 most effective derivative based preliminary activity screening in vitro, with no obvious toxicity after administration vivo . Method: The study aimed to determine pharmacokinetics, tissue distribution, hepatotoxicity, nephrotoxicity, compound non-small cell lung cancer (NSCLC) vitro Results: pharmacokinetics parameters were better than those ZLDI-8. distribution analysis showed that tail vein injection 6 mg/kg rats resulted highest concentration lung, so we hypothesized might be treatment cancer. In assays significantly inhibited tumor colony formation, invasion, migration increased LDH apoptosis concentration-dependent manner cells. also formation metastases without significant major organs nude mice. Conclusion: Compared parent compound, safety higher. ADAM17 simultaneously affects downstream Notch1 integrinβ1 pathways resulting activity. Thus, could potential agent, inhibiting organization development