Calcipotriol

HCID 5288783

Grundinformationen

CAS
112828-00-9
Standard-SMILES
C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)/C=C/[C@@H](O)C4CC4)CC[C@@H]23)C[C@@H](O)C[C@@H]1O
InChIKey
LWQQLNNNIPYSNX-UROSTWAQSA-N
Summenformel
C27H40O3
Durchschnittliche Molmasse
412,6 g/mol
Monoisotopische Masse
412,29774514

Überblick

Calcipotriol is a seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. It has a role as an antipsoriatic and a drug allergen. It is a triol, a secondary alcohol, a seco-cholestane, a hydroxy seco-steroid and a member of cyclopropanes.

Namen und Bezeichner

Bevorzugter Name
Calcipotriol
IUPAC
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Englischer Name
Calcipotriene
Summenformel
C27H40O3
Molmasse
412.6

Namen und Synonyme

Calcipotriolcalcipotriene112965-21-6DovonexCalciptriolDaivonexCalcitreneMC-903Calcipotriol anhydrousPRI-2201DTXSID0046648CHEBI:50749
Weitere Namen anzeigen
Calcipotriol hydrateDaivobetcipotrieneCalcipotrio
143NQ3779B(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diolMC903(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol9,10-Secochola-5,7,10(19),22-tetraene-1,3,24-triol, 24-cyclopropyl-, (1alpha,3beta,5Z,7E,22E,24S)-DTXCID8026648calcipotriolocalcipotriolum

Datenbank-Bezeichner

CAS
112828-00-9、112965-21-6
PubChem CID
5288783
DTXSID
DTXSID0046648
ChEMBL
CHEMBL1200666
ChEBI
CHEBI:50749
UNII
143NQ3779B
EC Number
601-218-4、686-849-3
Nikkaji
J367.434G

Eigenschaften

Berechnete Struktureigenschaften

XLogP
4,3
Polarare Oberfläche (TPSA)
60,7 Ų
H-Brücken-Donoren
3
H-Brücken-Akzeptoren
3
Frei drehbare Bindungen
5
Schwere Atome
30

Experimentelle und physikochemische Eigenschaften

DrugsPharmaceuticals -> Listed in ZINC15
LipidsLipids -> Sterol Lipids [ST] -> Secosteroids [ST03] -> Vitamin D3 and derivatives [ST0302]
Solubility1.35e-02 g/L
Human Drugs · 4 Einträge

Breast Feeding; Lactation; Milk, Human; Dermatologic Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Dermatological medicines > Medicines affecting skin differentiation and proliferation

Physical DescriptionSolid

Physikochemische Eigenschaften

Schmelzpunkt
166 · 166-168°C
Siedepunkt
582 · 582.0±50.0 °C(Predicted)
Dichte
1.12 · 1.12±0.1 g/cm3(Predicted)
storage temp.
-20 °C · Desiccate at -20°C
Löslichkeit
15 mg/mL, · DMSO: soluble15mg/mL, clear
Aggregatzustand
powder

Sicherheit und Regulatorisches

GHS-Klassifizierung

GHS Classification · 6 Einträge

Danger

H300+H310 (16.7%): Fatal if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]

P203, P260, P261, P262, P263, P264, P264+P265, P270, P271, P272, P280, P284, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P320, P321, P330, P332+P317, P333+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 6 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

Gefahrenhinweise

Hazard Classes and Categories · 2 Einträge

Acute Tox. 2 (83.3%)

Acute Tox. 3 (100%)

Toxikologische Informationen

Exposure Routes · 1 Eintrag

Clinical studies with radiolabeled ointment indicate that approximately 6% (+3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (+2.6%, SO) when applied to normal skin.

Toxicity Summary · 1 Eintrag

The precise mechanism of calcipotriol in remitting psoriasis is not well-understood. However, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor, while being less than 1% as active as the calcitriol in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes.

Signs and SymptomsTopically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of calcipotriene.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

Sicherheitsdaten

wgk
3
ridadr
UN 2811 6.1 / PGIII
hs_code
2906195000
risk_code
36/37/38
Toxizität
dog,LD50,skin,> 1500ug/kg (1.5mg/kg),BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)MUSCULOSKELETAL: OTHER CHANGESGASTROINTESTINAL: NAUSEA OR VOMITING,Journal of Toxicological Sciences. Vol. 21(Suppl,
hazard_code
Xi

Chemie und Industrie

Pharmakologische Informationen

ATC Code · 4 Einträge

D05AX52

D - Dermatologicals

QD - Dermatologicals

D05AX02

PharmacodynamicsCalcipotriene is a synthetic analog of vitamin D. In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin.
Mechanism of Action · 1 Eintrag

The precise mechanism of calcipotriol in remitting psoriasis is not well-understood, however, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor while being less than 1% the activity in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis and are believed to undergo modulation of gene expression with binding of calcipotriol to the VDR. This modulation is thought to affect gene products related to cell differentiation and proliferation.

Metabolism/Metabolites · 2 Einträge

Hepatic. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound.

Hepatic. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound. Route of Elimination: The active form of the vitamin, 1,25-dihydroxy vitamin D3 (calcitriol), is known to be recycled via the liver and excreted in the bile. There is evidence that maternal 1,25-dihydroxy vitamin D3 (calcitriol) may enter the fetal circulation, but it is not known whether it is excreted in human milk.

FDA Pharmacological Classification · 6 Einträge

143NQ3779B

CALCIPOTRIENE

Chemical Structure [CS] - Vitamin D

Established Pharmacologic Class [EPC] - Vitamin D Analog

Calcipotriene is a Vitamin D Analog.

CALCIPOTRIENE

MeSH Pharmacological ClassificationDrugs used to treat or prevent skin disorders or for the routine care of skin.

Verwendung und Herstellung

Uses · 2 Einträge

Use (kg) in USA (2002): 4

For the treatment of moderate plaque psoriasis in adults.

Anwendungen · 2 Einträge

BeschreibungCalcipotriene also known as Calcipotriol, is a topical vitaminD3 derivative effective in the treatment of psoriasis vulgaris. The drug acts by binding to vitamin D3 receptors in the skin keratinocytes, producing an elevation in cell differentiation and a reduction in cell proliferation. Although its efficacy is comparable to calcitriol, calcipotriol exhibits at least 100 times less effect on calcium metabolism in rats.

VerwendenCalcipotriene is an antipsoriatic that is a vitamin D3 analogue with low calcemic activity. It works by regulating the production and growth of skin cells. In the United States, this drug was first marketed under the trade name Dovonex and is used mainly for the treatment of psoriasis. It is one of the most effective non glucocorticoid topical drugs for the treatment of localized psoriasis.This drug has many off-label applications that are alternative therapies for many dermatologic diseases.

Darstellung · 1 Eintrag

synthetischeA convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven Vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described.A Synthesis of calcipotriol via a Key Electroreductive Cross-coupling ApproachCalcipotriol is currently the most successful VitD analog and is prescribed for the treatment of psoriasis, an autoimmune skin disease.

Anbieter100 Anbieter

北京华美互利生物化工010-56205725 · [email protected]
天津始加生物医药科技有限公司15022261580 · [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]
Ergänzende Hinweise · 1 Eintrag

DefinitionChEBI: Calcipotriol is a seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. It has a role as a drug allergen and an antipsoriatic. It is a member of cyclopropanes, a secondary alcohol, a triol, a hydroxy seco-steroid and a seco-cholestane.

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