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Background <p>Histone deacetylases (HDAC) are involved in chromatin remodelling, and histone deacetylases inhibitors have become the interest of research and shown promising antitumor effects against various cancer.</p> Methods <p>In the current study, an attempt was made to characterize the preclinical ADME properties of a novel hydroxamic based HDAC inhibitor, PAT-1102, with the help of in vitro assays and in vivo pharmacokinetic experiments in rats.</p> Results <p>PAT-1102 showed high aqueous solubility and high Caco-2 permeability in the in vitro assays. It was found to be not a substrate of efflux protein P-gp, found stable in metabolism experiments with incubations of rat and human liver microsomes. Inhibition experiments of human recombinant CYP enzymes revealed that PAT-1102 was not considerably inhibited the major CYP enzymes. PAT-1102 exhibited low plasma protein binding of 58.1% and 54.5% in humans and rats, respectively. In vivo pharmacokinetic studies of PAT-1102 in male and female rats showed bioavailability of 3.7% and 3.0% by oral route, respectively. Previous research findings suggested that PAT-1102 is a potent pan-HDAC inhibitor with good preclinical efficacy.</p> Conclusion <p>Considering the overall ADME and pharmacokinetic profile of PAT-1102, as indicated by in vitro and in vivo experiments, the PAT-1102 could be considered as a potential candidate for the advancement of cancer therapy.</p>

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Preclinical pharmacokinetics and in vitro ADME properties of PAT-1102: a novel HDAC inhibitor for cancer therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月24日

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  • Chandrashekar Mataguru Doreswamy,
  • Srinivas Seekallu,
  • Suresh Babu Venkataramaiah,
  • Mohan Cheluru Umesh,
  • C. Subathra Devi

摘要

Background

Histone deacetylases (HDAC) are involved in chromatin remodelling, and histone deacetylases inhibitors have become the interest of research and shown promising antitumor effects against various cancer.

Methods

In the current study, an attempt was made to characterize the preclinical ADME properties of a novel hydroxamic based HDAC inhibitor, PAT-1102, with the help of in vitro assays and in vivo pharmacokinetic experiments in rats.

Results

PAT-1102 showed high aqueous solubility and high Caco-2 permeability in the in vitro assays. It was found to be not a substrate of efflux protein P-gp, found stable in metabolism experiments with incubations of rat and human liver microsomes. Inhibition experiments of human recombinant CYP enzymes revealed that PAT-1102 was not considerably inhibited the major CYP enzymes. PAT-1102 exhibited low plasma protein binding of 58.1% and 54.5% in humans and rats, respectively. In vivo pharmacokinetic studies of PAT-1102 in male and female rats showed bioavailability of 3.7% and 3.0% by oral route, respectively. Previous research findings suggested that PAT-1102 is a potent pan-HDAC inhibitor with good preclinical efficacy.

Conclusion

Considering the overall ADME and pharmacokinetic profile of PAT-1102, as indicated by in vitro and in vivo experiments, the PAT-1102 could be considered as a potential candidate for the advancement of cancer therapy.