Structure and the Anticancer Activity of Vitamin D Receptor Agonists

• Published in: International journal of molecular sciences Vol. 25; no. 12; p. 6624
• Main Authors: Powała, Agnieszka, Żołek, Teresa, Brown, Geoffrey, Kutner, Andrzej
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2024; MDPI
• Subjects: Alfacalcidol; Amino acids; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological activity; Calcifediol; calcitriol; Calcitriol - analogs & derivatives; Calcitriol - chemistry; Calcitriol - pharmacology; Cancer; Cell differentiation; Enzymes; Fish oils; Genes; Homeostasis; Humans; Hydrogen bonds; Immune system; Liver; Metabolism; Neoplasms - drug therapy; Neoplasms - metabolism; Phosphates; Physiological aspects; Physiology; Radiation; Receptors, Calcitriol - agonists; Receptors, Calcitriol - metabolism; Review; Rickets; Skin; Steroids; Structure-Activity Relationship; VDR ligand-binding domain; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - chemistry; Vitamin D - pharmacology; vitamin D anticancer analogs; vitamin D metabolites and analogs; vitamin D receptor (VDR); vitamin D anticancer analogs; vitamin D metabolites and analogs; VDR ligand-binding domain; calcitriol; vitamin D; vitamin D receptor (VDR)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126624

Vitamin D is a group of seco-steroidal fat-soluble compounds. The two basic forms, vitamin D (ergocalciferol) and vitamin D (cholecalciferol), do not have biological activity. They are converted in the body by a two-step enzymatic hydroxylation into biologically active forms, 1α,25-dihydroxyvitamin D [ercalcitriol, 1,25(OH) D ] and 1α,25-dihydroxyvitamin D [calcitriol, 1,25(OH) D ], which act as classical steroid hormones. 1,25(OH) D exerts most of its physiological functions by binding to the nuclear vitamin D receptor (VDR), which is present in most body tissues to provide support to a broad range of physiological processes. Vitamin D-liganded VDR controls the expression of many genes. High levels of 1,25(OH) D cause an increase in calcium in the blood, which can lead to harmful hypercalcemia. Several analogs of 1,25(OH) D and 1,25(OH) D have been designed and synthesized with the aim of developing compounds that have a specific therapeutic function, for example, with potent anticancer activity and a reduced toxic calcemic effect. Particular structural modifications to vitamin D analogs have led to increased anticancer activity and reduced calcemic action with the prospect of extending work to provide future innovative therapies.