25-nitro-20-epi-vitamin D analogue with anti-proliferative and cytoprotective properties: Biological and pharmacological evaluation

IF 4.1 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-02-23 DOI:10.1016/j.yexmp.2026.105036

Uxía Gómez-Bouzó , Carole Peluso-Iltis , Sandra Barreiro , Carlos Fernandes , Lieve Verlinden , Annemieke Verstuyf , Fernanda Borges , Natacha Rochel , Generosa Gómez , Yagamare Fall

{"title":"25-nitro-20-epi-vitamin D analogue with anti-proliferative and cytoprotective properties: Biological and pharmacological evaluation","authors":"Uxía Gómez-Bouzó , Carole Peluso-Iltis , Sandra Barreiro , Carlos Fernandes , Lieve Verlinden , Annemieke Verstuyf , Fernanda Borges , Natacha Rochel , Generosa Gómez , Yagamare Fall","doi":"10.1016/j.yexmp.2026.105036","DOIUrl":null,"url":null,"abstract":"<div><div>We report the synthesis and pharmacological evaluation of <strong>UG-635</strong>, a novel 25-nitro vitamin D analogue bearing a 20-epimeric configuration. Cytotoxicity studies in SH-SY5Y neuroblastoma and HepG2 hepatocarcinoma cells showed that <strong>UG-635</strong> is well tolerated at low concentrations but reduces viability at higher doses. Importantly, <strong>UG-635</strong> demonstrated protective effects against oxidative stress in neuronal cells and exhibited anti-proliferative activity in breast cancer (MCF7) and osteoblast (MC3T3-E1) models, with efficacy comparable to calcitriol. Structural and crystallographic analyses revealed efficient binding to the vitamin D receptor (VDR), stabilizing its active conformation through favorable interactions with anchoring histidines. These findings highlight <strong>UG-635</strong> as a promising vitamin D analogue with potential pharmacological relevance in cancer and neurodegenerative disease contexts, combining anti-proliferative and cytoprotective properties.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105036"},"PeriodicalIF":4.1000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and molecular pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014480026000158","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

We report the synthesis and pharmacological evaluation of UG-635, a novel 25-nitro vitamin D analogue bearing a 20-epimeric configuration. Cytotoxicity studies in SH-SY5Y neuroblastoma and HepG2 hepatocarcinoma cells showed that UG-635 is well tolerated at low concentrations but reduces viability at higher doses. Importantly, UG-635 demonstrated protective effects against oxidative stress in neuronal cells and exhibited anti-proliferative activity in breast cancer (MCF7) and osteoblast (MC3T3-E1) models, with efficacy comparable to calcitriol. Structural and crystallographic analyses revealed efficient binding to the vitamin D receptor (VDR), stabilizing its active conformation through favorable interactions with anchoring histidines. These findings highlight UG-635 as a promising vitamin D analogue with potential pharmacological relevance in cancer and neurodegenerative disease contexts, combining anti-proliferative and cytoprotective properties.

Abstract Image

查看原文本刊更多论文

具有抗增殖和细胞保护特性的25-硝基-20-外延维生素D类似物：生物学和药理学评价。

我们报道了UG-635的合成和药理学评价，UG-635是一种新型的25硝基维生素D类似物，具有20外聚体结构。SH-SY5Y神经母细胞瘤和HepG2肝癌细胞的细胞毒性研究表明，UG-635在低浓度下具有良好的耐受性，但在高剂量下会降低生存能力。重要的是，UG-635在神经元细胞中表现出抗氧化应激的保护作用，并在乳腺癌（MCF7）和成骨细胞（MC3T3-E1）模型中表现出抗增殖活性，其疗效与骨化三醇相当。结构和晶体学分析表明，它与维生素D受体（VDR）有效结合，通过与锚定组氨酸的有利相互作用稳定其活性构象。这些发现突出了UG-635作为一种有前途的维生素D类似物，在癌症和神经退行性疾病背景下具有潜在的药理意义，具有抗增殖和细胞保护特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Experimental and molecular pathology 医学-病理学

CiteScore

8.90

自引率

0.00%

发文量

审稿时长

11.5 weeks

期刊介绍： Under new editorial leadership, Experimental and Molecular Pathology presents original articles on disease processes in relation to structural and biochemical alterations in mammalian tissues and fluids and on the application of newer techniques of molecular biology to problems of pathology in humans and other animals. The journal also publishes selected interpretive synthesis reviews by bench level investigators working at the "cutting edge" of contemporary research in pathology. In addition, special thematic issues present original research reports that unravel some of Nature''s most jealously guarded secrets on the pathologic basis of disease. Research Areas include: Stem cells; Neoangiogenesis; Molecular diagnostics; Polymerase chain reaction; In situ hybridization; DNA sequencing; Cell receptors; Carcinogenesis; Pathobiology of neoplasia; Complex infectious diseases; Transplantation; Cytokines; Flow cytomeric analysis; Inflammation; Cellular injury; Immunology and hypersensitivity; Athersclerosis.