Doxercalciferol

HCID 5281107
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Basic information

CAS
54573-75-0
Standard SMILES
C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@@H]23)C[C@@H](O)C[C@@H]1O
InChIKey
HKXBNHCUPKIYDM-CGMHZMFXSA-N
Molecular formula
C28H44O2
Average molar mass
412.6 g/mol
Monoisotopic mass
412.33413065

Overview

Doxercalciferol is a hydroxy seco-steroid and synthetic vitamin D2 analogue that undergoes metabolic activation in vivo to form 1alpha,25-dihydroxyvitamin D2 (1alpha,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. It is used to treat secondary hyperparathyroidism, a condition in which the body produces excess parathyroid hormone (PTH; a natural substance needed to control the amount of calcium in the blood) in certain people with chronic kidney disease. It has a role as a provitamin, a bone density conservation agent and a prohormone. It is a vitamin D and a hydroxy seco-steroid.

Names & identifiers

Preferred name
Doxercalciferol
IUPAC
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
English name
Doxercalciferol
Molecular formula
C28H44O2
Molecular weight
412.65

Names & synonyms

Doxercalciferol54573-75-0Hectorol1-Hydroxyergocalciferol1alpha-Hydroxyergocalciferol1alpha-hydroxyvitamin D21-alpha-Hydroxyvitamin D21-alpha-hydroxyergocalciferolDoxercalciferolum3DIZ9LF5Y9(1S,3R,5Z,7E,22E)-9,10-Secoergosta-5,7,10,22-tetraene-1,3-diol(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Show more names
C08211TSA 8401α-OHD2ERCALCIDOLDocalcitol1ALPHA-OH-D2DoxecalciferolDoxercalcifero
TSA-840GZ427397CHEBI:4712doxacalciferol9,10-Secoergosta-5,7,10(19),22-tetraene-1,3-diol, (1alpha,3beta,5Z,7E,22E)-1alpha-OHD21alpha(OH)2D2H05BX03

Database identifiers

CAS
54573-75-0
PubChem CID
5281107
DTXSID
DTXSID1034214
ChEMBL
CHEMBL1200810
ChEBI
CHEBI:4712
UNII
3DIZ9LF5Y9
EC Number
643-005-9
Nikkaji
J527.612H

Properties

Computed structural properties

XLogP
6.3
Topological polar surface area
40.5 Ų
Hydrogen bond donors
2
Hydrogen bond acceptors
2
Rotatable bonds
5
Heavy atoms
30

Experimental & physicochemical properties

LipidsLipids -> Sterol Lipids [ST] -> Secosteroids [ST03] -> Vitamin D2 and derivatives [ST0301]
SolubilityRelatively insoluble
Human Drugs · 2 items

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Physicochemical properties

Melting point
138 · 138-140°C
Boiling point
538.7 · 538.7±50.0 °C(Predicted)
Density
1.01 · 1.01±0.1 g/cm3(Predicted)
storage temp.
-20 °C · Sealed in dry,Store in freezer, under -20°C
solubility
10 mg/mL · DMSO: >10mg/mL
form
White crystalline solid

Safety & regulation

GHS classification

GHS Classification · 4 items

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 51 reports by companies from 2 notifications to the ECHA C&L Inventory.

Hazard information

Hazard Classes and CategoriesAcute Tox. 1 (100%)

Toxicology

Drug Induced Liver Injury · 6 items

Drug Induced Liver Injury Rank (DILIrank 2.0)

Doxercalciferol

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Safety data

wgk
3
rtecs
VS2950000
ridadr
UN 2811 6.1 / PGIII
hs_code
2936299055
Toxicity
LD50 orally in rats: 3.5-6.5 mg/kg (Sjden)
risk_code
28

Chemistry & industry

Pharmacology

ATC Code · 2 items

H - Systemic hormonal preparations, excl. sex hormones and insulins

QH - Systemic hormonal preparations, excl. sex hormones and insulin

Mechanism of Action · 1 item

Calcitriol (1α,25-(OH)2D3) and 1α,25-(OH)2D2 regulate blood calcium at levels required for essential body functions. Specifically, the biologically active vitamin D metabolites control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. They act directly on bone cells (osteoblasts) to stimulate skeletal growth, and on the parathyroid glands to suppress PTH (parathyroid hormone) synthesis and secretion. These functions are mediated by the interaction of these biologically active metabolites with specific receptor proteins in the various target tissues. In patients with chronic kidney disease (CKD), deficient production of biologically active vitamin D metabolites (due to lack of or insufficient 25-hydroxyvitamin D-1-alpha-hydroxylase activity) leads to secondary hyperparathyroidism, which contributes to the development of metabolic bone disease.

Biological Half-Life32 to 37 hours.
Metabolism/Metabolites · 1 item

Doxercalciferol is absorbed from the gastrointestinal tract and activated by CYP 27 in the liver to form 1α,25-(OH)2D2 (major metabolite) and 1α,24-dihydroxyvitamin D2 (minor metabolite). Activation of doxercalciferol does not require the involvement of the kidneys.

FDA Pharmacological Classification · 6 items

3DIZ9LF5Y9

DOXERCALCIFEROL

Chemical Structure [CS] - Ergocalciferols

Established Pharmacologic Class [EPC] - Vitamin D2 Analog

Doxercalciferol is a Vitamin D2 Analog.

DOXERCALCIFEROL

MeSH Pharmacological Classification · 2 items

Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.

Applications · 2 items

DescriptionDoxercalciferol is a synthetic vitamin D2 analog introduced in the US as Hectorol for the treatment of secondary hyperparathyroidism (SHPT) in patients with end-stage renal failure. It is actually 1-alpha-hydroxyvitamin D2 (one-alpha- D2) and can be synthesized by direct hydroxylation of vitamin D2 tosylate or in 5 steps from ergosterol. Doxercalciferol itself is inactive until metabolized by the liver into active 1,24-dihydroxyvitamin D2, showing a pharmacokinetic profile similar to calcitriol. During placebo-controlled clinical trials, patients with moderate to severe SHPT were treated with 1-alpha-D2 (10 μg doses) for 16 to 24 weeks; in 9 patients out of 10, blood levels of parathyroid hormone were considerably reduced, so maintaining a good control of the parathyroid hyperplasia. Moreover, only a moderate tendency to raise calcium and phosphate was observed. Doxercalciferol is orally-active and less toxic than other vitamin D analogs like alfacalcidol; it shows differentially controlled effects and has an improved safety profile compared to calcitriol.

UsesSynthetic vitamin D prohormone. A new active Vitamin D analog which inhibits growth of human neuroblastoma. Antihyperparathyroid

Upstream & downstream products

Suppliers100 total

北京华美互利生物化工010-56205725 · [email protected]
上海阿拉丁生化科技股份有限公司400-6206333 13167063860 · [email protected]
上海策嵘生物科技有限公司[email protected]
济南百隆化学有限公司[email protected] · [email protected]
成都彼样生物科技有限公司18108052721 · [email protected]
Additional notes · 1 item

DefinitionChEBI: Doxercalciferol is a hydroxy seco-steroid and synthetic vitamin D2 analogue that undergoes metabolic activation in vivo to form 1alpha,25-dihydroxyvitamin D2 (1alpha,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. It is used to treat secondary hyperparathyroidism, a condition in which the body produces excess parathyroid hormone (PTH; a natural substance needed to control the amount of calcium in the blood) in certain people with chronic kidney disease. It has a role as a provitamin, a bone density conservation agent and a prohormone. It is a vitamin D and a hydroxy seco-steroid.

Related reactions

5 records
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Compound notes

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