膵管腺癌におけるLXR受容体を介した阻害機構：分子ドッキング・分子動力学・分子間接触解析を統合した計算科学的アプローチ
Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis owing to its aggressive biology and limited options at advanced stages. Liver X receptors (LXRα and LXRβ), nuclear receptors governing cholesterol, lipid, and glucose metabolism as well as inflammatory signaling, have been identified as candidate targets in PDAC. This in silico study evaluated three natural compounds—Baicalein, Beta-Sitosterol, and Polydatin—as potential LXR inhibitors using molecular docking, molecular dynamics simulations, and post-MD intermolecular hydrogen-bond contact analyses. Baicalein demonstrated broad inhibitory activity against both LXRα and LXRβ, whereas Beta-Sitosterol showed particularly strong binding affinity for LXRβ. The authors propose that these findings provide a mechanistic basis for subsequent in vitro and in vivo studies aimed at clarifying how LXR suppression may impede PDAC progression.
Baicalein is proposed to inhibit both LXRα and LXRβ through direct receptor binding, while Beta-Sitosterol selectively targets LXRβ; suppression of these nuclear receptors is expected to downregulate cholesterol and lipid metabolism gene expression, thereby impeding PDAC cell proliferation.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/38156844