MAXACALCITOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H42O4
Molecular Weight	418.6093
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)OCCC(C)(C)O

InChI

InChIKey=DTXXSJZBSTYZKE-ZDQKKZTESA-N

InChI=1S/C26H42O4/c1-17-20(15-21(27)16-24(17)28)9-8-19-7-6-12-26(5)22(10-11-23(19)26)18(2)30-14-13-25(3,4)29/h8-9,18,21-24,27-29H,1,6-7,10-16H2,2-5H3/b19-8+,20-9-/t18-,21+,22+,23-,24-,26+/m0/s1

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Description
Sources: https://chugai-pharm.jp/hc/ss/pr/drug/oxa_amp0100/shiori/PDF/en/oxa_s_en.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12617040 | https://www.chugai-pharm.co.jp/english/news/detail/20081128000000.html

Maxacalcitol (OXAROL®) is a derivative of vitamin D and is used to treat the secondary hyperparathyroidism of hemodialysis (HD) patients as an injection and psoriasis as an ointment. Secondary hyperparathyroidism is one of the complications in HD patients with hyperplasia of parathyroid glands and elevated serum parathyroid hormone (PTH) levels. Maxacalcitol (OXAROL®) suppresses synthesis and secretion of parathyroid hormone, and decreases a concentration of parathyroid hormone in blood. It also inhibits proliferation and induces differentiation of epidermal keratinocytes. Maxacalcitol (OXAROL®) used in patients with keratosis including psoriasis vulgaris, remarkably improving the symptoms.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12617040	Agonist 2678		37.9 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Secondary hyperparathyroidism 9 Sources: https://chugai-pharm.jp/hc/ss/pr/drug/oxa_amp0100/shiori/PDF/en/oxa_s_en.pdf	Primary	Approved 8429	OXAROL Approved Use It is usually used to treat secondary hyperparathyroidism of the patient on dialysis.
Psoriasis vulgaris 5 Sources: https://www.chugai-pharm.co.jp/english/news/detail/20081128000000.html	Palliative	Approved 8429	OXAROL Approved Use Treatment drug for keratosis including psoriasis vulgaris.
Palmoplantar pustulosis 1 Sources: https://www.chugai-pharm.co.jp/english/news/detail/20081128000000.html	Palliative	Approved 8429	OXAROL Approved Use Treatment of palmoplantar pustulosis.

PubMed

Title	Date	PubMed
A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia.	1991 Aug	1855478
Effects of two new vitamin D3 derivatives, 22-oxa-1 alpha-25-dihydroxyvitamin D3 (OCT) and 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71), on bone metabolism in organ culture.	1993	8443002
Differential effects of 1,25-(OH)2D3 and 22-oxacalcitriol on phosphate and calcium metabolism.	1993 Mar	8455354
Actions of vitamin D3, analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3.	1995 Jan	7530193
Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: results of a preliminary study.	1996	8840326
22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.	1999 Mar	10027919
Clinical effects of maxacalcitol on secondary hyperparathyroidism of uremic patients.	2001 Oct	11576942
Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic patient with diabetic nephropathy; a case report and analysis of the potential for hypercalcemia.	2003 Dec	14714959
Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines.	2005 Oct	16039115
Comparison of the efficacy of an oral calcitriol pulse or intravenous 22-oxacalcitriol therapies in chronic hemodialysis patients.	2005 Sep	16189633
Hypercalcemia caused by vitamin D3 analogs in psoriasis treatment.	2007 Dec	18173537
Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats.	2009 Aug	19297354

Patents

Sample Use Guides

In Vivo Use Guide

Inject Oxarol® at a venous side of dialysis circuit just before the completion of dialysis three times a week. Appropriate amount of Oxarol® product (ointment, lotion) should be applied to the affected area twice daily.

Route of Administration: Other

In Vitro Use Guide

To investigate the activation of the vitamin D receptor (VDR) by 20S,24R(OH)2D3 and 20S,24S(OH)2D3 together with their 1a-OH derivatives, two cell lines (HaCaT and Caco-2) were transduced by a lentiviral VDRE luciferase reporter vector. 1,25-(OH)2D3 and 22-oxa-1,25(OH)2D3 (maxacalcitol) were used as positive controls. Both 1,25-(OH)2D3 and maxacalcitol showed the expected strong activations of VDRE in both cell lines, with the EC50 values showing that maxacalcitol (HaCaT EC50=37.9 ± 1.2 nM, Caco-2 EC50=40.8 ± 1.7 nM) is more potent than 1,25(OH)2D3 (HaCaT EC50=321.5 ± 14.2 nM, Caco-2 EC50=515.2 ± 22.4 nM).

Name

Type

Language

MAXACALCITOL

Official Name

English

OXAROL

Brand Name

English

OCT

Code

English

22-OXACALCITRIOL

Common Name

English

MAXACALCITOL [JAN]

Common Name

English

(1S-(1.ALPHA.(R*),3A.BETA.,4E(1S*,3R*,5Z),7A.ALPHA.))-4-METHYLENE-5-(2-(OCTAHYDRO-1-(1-(3-HYDROXY-3-METHYLBUTOXY)ETHYL)-7A-METHYL-4H-INDEN-4-YLIDIENE)ETHYLIDENE-1,3-CYCLOHEXANEDIOL

Common Name

English

SCH209579

Code

English

MAXACALCITOL [USAN]

Common Name

English

(+)-(5Z,7E,20S)-20-(3-HYDROXY-3-METHYLBUTOXY)-9,10-SECOPREGNA-5,7,10(19)-TRIENE-1.ALPHA.,3.BETA.-DIOL

Common Name

English

maxacalcitol [INN]

Common Name

English

Maxacalcitol [WHO-DD]

Common Name

English

MAXACALCITOL [MI]

Common Name

English

MAXACALCITOL [MART.]

Common Name

English

SCH-209579

Code

English

PREZIOS

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C39713