Departamento de Química Orgánica, Laboratorio de Investigación Ignacio Ribas, Universidad de Santiago de Compostela, Avda das Ciencias s/n, 15782 Santiago de Compostela, Spain.
LEO Pharma, Open Innovation, Industriparken 55, 2750 Ballerup, Denmark.
Bioorg Chem. 2021 Oct;115:105202. doi: 10.1016/j.bioorg.2021.105202. Epub 2021 Jul 22.
A high number of biologically active and low-calcemic secosteroidal ligands of the vitamin D receptor (VDR) have been developed, some of which are already used clinically although with limited success in the treatment of hyperproliferative diseases because the required pharmaceutical dosages induce toxicity. We describe here the in silico design, synthesis, structural analysis and biological evaluation of two novel active lithocholic acid derivatives hydroxylated at the side chain as highly potent inhibitors of atopic dermatitis-relevant keratinocyte inflammation of potential therapeutic interest.
已经开发出了大量具有生物活性和低钙cemic 的维生素 D 受体 (VDR) 的甾体配体，其中一些已经在临床上使用，尽管在治疗过度增生性疾病方面取得的成功有限，因为所需的药物剂量会引起毒性。我们在这里描述了两种新型活性胆酸衍生物的计算机设计、合成、结构分析和生物学评价，这些衍生物在侧链上羟基化，是潜在治疗相关角蛋白细胞炎症的潜在治疗靶点。
