Patel Rajiv, Kharkwal Harsha, Saha Moumita, Sankaranarayanan Murugesan, Sharma Saurabh, Chander Subhash
Amity Institute of Phytochemistry & Phytomedicine, Amity University Uttar Pradesh, Noida 201313, India.
Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida 201313, India.
Biomedicines. 2025 Apr 21;13(4):1002. doi: 10.3390/biomedicines13041002.
Vitamin D and its metabolites are essential in various physiological processes, including muscle strength, metabolism, antifibrotic activity, and immune regulation. Researchers are focusing on developing vitamin D derivatives with optimized receptor selectivity and reduced systemic toxicity, enhancing their therapeutic efficacy against cancer, autoimmune disorders, and inflammatory diseases. Several analogues, such as alfacalcidol, paricalcitol, and falecalcitriol, are used for managing CKD-related bone disorders, while eldecalcitol is effective for osteoporosis, and calcipotriol against psoriasis. Recent studies have explored their impact on metabolic pathways, parathyroid hormone secretion, asthma, and liver fibrosis, revealing their broad clinical potential. Despite enormous efforts in the past decades, translations of vitamin D-drugs are disproportionately limited, mainly due to toxicity due to calcemic effects and undesirable metabolic profile. This review discusses structural modifications in vitamin D3, their influence on VDR binding, transcriptional activity, and calcium homeostasis, along with their role in targeting pathways like EGFR, KRAS, and Hedgehog in cancers. Advanced analytical techniques such as LC/ESI-MS/MS facilitate precise detection of vitamin D metabolites, further improving pharmacokinetic profiling. Future research may enable the clinical approval of novel vitamin D-based therapeutics with minimal disruption to calcium-phosphorus balance.
维生素D及其代谢产物在多种生理过程中至关重要，包括肌肉力量、新陈代谢、抗纤维化活性和免疫调节。研究人员正致力于开发具有优化受体选择性和降低全身毒性的维生素D衍生物，以提高其对癌症、自身免疫性疾病和炎症性疾病的治疗效果。几种类似物，如阿法骨化醇、帕立骨化醇和度骨化醇，用于治疗与慢性肾脏病相关的骨疾病，而依替膦酸二钠对骨质疏松症有效，卡泊三醇对银屑病有效。最近的研究探讨了它们对代谢途径、甲状旁腺激素分泌、哮喘和肝纤维化的影响，揭示了它们广泛的临床潜力。尽管在过去几十年中付出了巨大努力，但维生素D药物的转化却极其有限，主要是由于其钙血症效应导致的毒性和不良的代谢特征。本综述讨论了维生素D3的结构修饰、它们对维生素D受体结合、转录活性和钙稳态的影响，以及它们在癌症中靶向表皮生长因子受体、KRAS和刺猬信号通路等途径中的作用。先进的分析技术，如液相色谱/电喷雾串联质谱，有助于精确检测维生素D代谢产物，进一步改善药代动力学特征。未来的研究可能会使新型维生素D类疗法在对钙磷平衡干扰最小的情况下获得临床批准。
