Reactome | VDR agonists bind VDR

VDR agonists bind VDR

Stable Identifier

R-HSA-9660192

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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The genomic mechanism of 1,25(OH)2D action involves the direct, high-affinity binding of 1,25(OH)2D-activated VDR/RXRA to specific vitamin D response elements (VDREs) in and around target genes resulting in either activation or repression of transcription (Christakos et al. 2016). Vitamin D receptor (VDR) agonist drugs function in the same way as 1,25(OH)2D, resulting in activation of gene transcription. VDR agonist drugs bind VDR and activate transcription of genes involved in calcium and bone homeostasis and proliferation and differentiation. These drugs are used to treat secondary hyperparathyroidism (SHPT), bone diseases such as osteoporosis, psoriasis and alopecia.

Paricalcitol (trade name Zemplar) is a VDR agonist drug used for the prevention and treatment of secondary hyperparathyroidism, SHPT, causing excessive secretion of parathyroid hormone associated with chronic renal failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol). However current evidence is not sufficient to demonstrate an advantage of paricalcitol over non-selective vitamin D derivatives for this indication (Cai et al. 2016, Xie et al. 2017). Doxercalciferol (trade name Hectorol) is a VDR agonist drug for secondary hyperparathyroidism and metabolic bone disease (Sprague & Ho 2002). It is a synthetic analog of ergocalciferol (vitamin D2). It suppresses parathyroid synthesis and secretion. Doxercalciferol needs a 25-hydroxylation step in the liver to become active and is independent of renal or extrarenal 1α-hydroxylase.

Eldecalcitol (trade name Edirol) is a VDR agonist drug used in Japan for the treatment of osteoporosis. Studies suggest Eldecalcitol reduces calcium reabsorption into the body from bones, therefore increasing bone mineral density, and increases calcium absorption in intestines (Matsumoto 2012, Noguchi et al. 2013). Calcipotriol (trade names Dovonex, Daivonex and Psorcutan) is a synthetic derivative of the active form of vitamin D, calcitriol. It is used in the long-term treatment of chronic plaque psoriasis (Salmhofer et al. 2000, Ito et al. 2016) and alopecia areata (Kim et al. 2012). Falecalcitriol (Ito et al. 2009) and maxacalcitol (Akizawa et al. 2015) are used to treat SHPT in Japan (Honda et al. 2014, Mizobuchi et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
26748501	Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials Cai, P, Li, Z, Ji, L, Tang, X, Qin, W	Int Urol Nephrol	2016
24569127	Active vitamin D analogs, maxacalcitol and alfacalcidol, as maintenance therapy for mild secondary hyperparathyroidism in hemodialysis patients - a randomized study Koiwa, F, Suzuki, R, Takahashi, K, Michihata, T, Shishido, K, Sekiguchi, T, Honda, H, Akizawa, T, Yamamoto, K, Ogata, H, Kinugasa, E, Ogawa, H, Kino, K, Kato, K, Mukai, M	Int J Clin Pharmacol Ther	2014
28005175	Research on kidney and mineral metabolism in Japan: past, present, and future Koiwa, F, Akizawa, T, Ogata, H, Kinugasa, E, Mizobuchi, M	Clin. Exp. Nephrol.	2017
22918710	Osteoporosis treatment by a new active vitamin D3 compound, eldecalcitol, in Japan Matsumoto, T	Curr Osteoporos Rep	2012
22879719	Successful treatment of alopecia areata with topical calcipotriol Kim, HM, Choi, SY, Lee, JW, Kim, DH, Kim, BJ, Kim, MN, Lim, YY, Kim, IS	Ann Dermatol	2012
25363733	Comparison of paricalcitol with maxacalcitol injection in Japanese hemodialysis patients with secondary hyperparathyroidism Hirakata, H, Fukagawa, M, Yokoyama, K, Akizawa, T, Zhang, W, Tominaga, Y, Kinugasa, E, Akiba, T, Suzuki, M, Linde, PG	Ther Apher Dial	2015
28841848	Comparative efficacy and safety of paricalcitol versus vitamin D receptor activators for dialysis patients with secondary hyperparathyroidism: a meta-analysis of randomized controlled trials Zhao, R, Li, L, Zhang, H, Su, P, Meng, L, Sun, Y, Xie, Y	BMC Nephrol	2017
24101867	Eldecalcitol for the treatment of osteoporosis Kawate, H, Noguchi, Y, Takayanagi, R, Nomura, M	Clin Interv Aging	2013
11234559	Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis Hödl, S, Maier, H, Soyer, HP, Hönigsmann, H, Salmhofer, W	Acta Derm Venereol Suppl (Stockh)	2000
12227689	Oral doxercalciferol therapy for secondary hyperparathyroidism in a peritoneal dialysis patient Ho, LT, Sprague, SM	Clin. Nephrol.	2002
19473635	Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial Takahashi, K, Ogata, H, Yamamoto, M, Ito, H, Kinugasa, E, Shishido, K, Taguchi, S, Takahashi, J	Clin. Nephrol.	2009
26434738	Proactive treatment with calcipotriol reduces recurrence of plaque psoriasis Tatematsu, S, Koga, M, Ito, K, Nakayama, J, Imafuku, S, Shibayama, Y	J. Dermatol.	2016