ALFACALCIDOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H44O2
Molecular Weight	400.6371
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3\C[C@@H](O)C[C@H](O)C3=C)[C@H](C)CCCC(C)C

InChI

InChIKey=OFHCOWSQAMBJIW-AVJTYSNKSA-N

InChI=1S/C27H44O2/c1-18(2)8-6-9-19(3)24-13-14-25-21(10-7-15-27(24,25)5)11-12-22-16-23(28)17-26(29)20(22)4/h11-12,18-19,23-26,28-29H,4,6-10,13-17H2,1-3,5H3/b21-11+,22-12-/t19-,23-,24-,25+,26+,27-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf
Curator's Comment: Description was created based on several sources, including http://www.sciencedirect.com/science/article/pii/B9780080552323611845 | https://www.ncbi.nlm.nih.gov/pubmed/19924035

Alfacalcidol (1-hydroxyvitamin D3) is a synthetic analog of vitamin D introduced clinically in the early 1970s. A prodrug for calcitriol (1,25-dihydroxyvitamin D3), it is one of the most potent and rapidly acting compounds currently used in the prevention and treatment of vitamin D deficiency states and hypocalcemia. The clinical benefit of alfacalcidol is related to the stimulation of calcium and phosphorus absorption, reversal of myopathy, promotion of mineralization in bone and the ability to reabsorb fully mineralized bone. Similar marketed vitamin D compounds include calcitriol and ergocalciferol. Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.drugbank.ca/drugs/DB01436#targets \| http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/19924035	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Renal osteodystrophy 11 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8429	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Hyperparathyroidism 1 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8429	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Hypoparathyroidism 5 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8429	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Rickets 3 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8429	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Osteomalacia 2 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8429	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia

PubMed

Title	Date	PubMed
[Transient vitamin-D dependent rickets? a case report differential diagnosis (author's transl)].	1982	6285251
Aspirin inhibition of 1 alpha-hydroxyvitamin D3 or parathyroid hormone induced hypercalcemia in vivo in rats. A mechanism independent of prostaglandin biosynthesis inhibition.	1985 Jun 1	4004906
Alfacalcidol as a modulator of growth of low grade non-Hodgkin's lymphomas.	1985 Oct 26	2996693
1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia.	1987 Jul	3037475
Possible role for vitamin D in controlling breast cancer cell proliferation.	1989 Jan 28	2563099
Danazol-induced hypercalcaemia in alphacalcidol-treated hypoparathyroidism.	1989 Nov	2616424
Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.	1991 Oct	1746944
Increase of renal 25-hydroxyvitamin D3-24-hydroxylase activity and its messenger ribonucleic acid level in 1 alpha-hydroxyvitamin D3-administered rats: possibility of the presence of two forms of 24-hydroxylase.	1993 Apr	8410379
Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: results of a preliminary study.	1996	8840326
Effect of 1 alpha-hydroxyvitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves' disease.	1997 Oct	9322804
Chronotherapy with active vitamin D3 in aged stroke-prone spontaneously hypertensive rats, a model of osteoporosis.	2001 Oct 5	11675047
Kidney microsomal 25- and 1alpha-hydroxylase in vitamin D metabolism: catalytic properties, molecular cloning, cellular localization and expression during development.	2002 Feb 28	11880238
Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia.	2004	15044820
1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro.	2005 Apr 20	15946915
Autosomal dominant hypocalcemia caused by an activating mutation of the calcium-sensing receptor gene: the first case report in Korea.	2010 Feb	20119591
Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats.	2010 Nov	20069278

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose for all indications: Adults: 1 microgram/day Dosage in the elderly: 0.5 microgram/day Neonates and premature infants: 0.05 – 0.1 microgram/kg/day Children under 20kg bodyweight: 0.05 microgram/kg/day Children over 20kg bodyweight: 1 microgram/day

Route of Administration: Oral

In Vitro Use Guide

Preincubation of aortic rings with alfacalcidol 10 uM significantly inhibited phenylephrine-induced contractions

Name

Type

Language

ALFACALCIDOL

Official Name

English

1.ALPHA.-HYDROXYCHOLECALCIFEROL [MI]

Common Name

English

1-HYDROXYVITAMIN D3

Common Name

English

ETALPHA

Brand Name

English

1.ALPHA.-HYDROXYCHOLECALCIFEROL

Common Name

English

1.ALPHA.-HYDROXYVITAMIN D3

Common Name

English

1-ALPHA-VITAMIN D

Common Name

English

1.ALPHA.(OH)D3

Common Name

English

1-HYDROXYCHOLECALCIFEROL

Common Name

English

(5Z,7E)-9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1.ALPHA.,3.BETA.-DIOL

Common Name

English

UN ALFA

Brand Name

English

1.ALPHA-HYDROXYCHOLECALCIFEROL

Common Name

English

UN ALPHA

Brand Name

English

ALFACALCIDOL [MART.]

Common Name

English

BONDIOL

Brand Name

English

ALFACALCIDOL [JAN]

Common Name

English

1,3-CYCLOHEXANEDIOL, 5-((2E)-2-((1R,3AS,7AR)-1-((1R)-1,5-DIMETHYLHEXYL)OCTAHYDRO-7A-METHYL-4H-INDEN-4-YLIDENE)ETHYLIDENE)-4-METHYLENE-, (1R,3R)-

Common Name

English

ALPHA D3

Brand Name

English

ALPHAROL

Brand Name

English

ALSIODOL

Brand Name

English

TEVABONE

Common Name

English

ALFACALCIDOL [EP MONOGRAPH]

Common Name

English

EINSALPHA

Brand Name

English

ALFAROL

Brand Name

English

OXYDEVIT

Brand Name

English

.ALPHA.-CALCIDOL

Common Name

English

alfacalcidol [INN]

Common Name

English

ALPHACALCIDOL

Brand Name

English

Alfacalcidol [WHO-DD]

Common Name

English

9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1,3-DIOL, (1.ALPHA.,3.BETA.,5Z,7E)-

Common Name

English

Classification Tree Code System Code

WHO-ATC

M05BB06