DT-Web

DB02300 - Calcipotriol


Identification
Name Calcipotriol
Accession Number DB02300 (EXPT02131)
Type small molecule
Description Calcipotriol (INN) or calcipotriene (USAN) is a sythetic derivative of calcitriol or Vitamin D.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 412.6047
Groups approved
Monoisotopic Weight 412.297745146
Pharmacology
Indication For the treatment of moderate plaque psoriasis in adults.
Mechanism of action 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.
Absorption 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.
Protein binding Not Available
Biotransformation 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.
Toxicity Topically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of calcipotriene.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Alfacalcidol Vitamin D Analogs may enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use.
Aluminum hydroxide Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid chronic and/or excessive use of aluminum and aluminum-containing products in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
Cholecalciferol Vitamin D Analogs may enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). hough not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
Orlistat Orlistat may decrease the serum concentration of fat soluble vitamins like vitamin D. Hence, this applies to calcipotriol, a synthetic derivative of vitamin D. Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Avoid concomitant administration due to the risk of impaired vitamin absorption. Similar precautions do not apply to parenterally administered fat soluble vitamins.
Sucralfate Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid chronic and/or excessive use of aluminum and aluminum-containing products (such as sucralfate) in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
Food Interactions Not Available

Targets


Vitamin D3 receptor
Name Vitamin D3 receptor
Gene Name VDR
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.2629

Enzymes


Myeloperoxidase
Name Myeloperoxidase
Gene Name MPO
Actions inhibitor
References
  • Sato H, Ogino Y, Takagi H, Hata J, Asano S, Ohta T, Komoriya K: Pharmacological profiles of high-concentration (20 microg/g) tacalcitol ointment: effects on cutaneous inflammation, epidermal proliferation, and differentiation in mice. J Dermatol. 2003 Jul;30(7):510-24. - Pubmed
DTHybrid score 0.3792
Cytochrome P450 24A1, mitochondrial
Name Cytochrome P450 24A1, mitochondrial
Gene Name CYP24A1
Actions substrate
References
  • Jones G, Byford V, West S, Masuda S, Ibrahim G, Kaufmann M, Knutson JC, Strugnell S, Mehta R: Hepatic activation and inactivation of clinically-relevant vitamin D analogs and prodrugs. Anticancer Res. 2006 Jul-Aug;26(4A):2589-95. - Pubmed
DTHybrid score 0.7119

Predictions


Id Partner name Gene Name Score
493 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial CYP27B1 0.319
4512 Cytochrome P450 3A4 CYP3A4 0.0958
6891 Mediator of RNA polymerase II transcription subunit 1 MED1 0.0935
581 Cytochrome P450 2R1 CYP2R1 0.0916
6228 Nuclear receptor coactivator 1 NCOA1 0.0897
606 Cytochrome P450 27, mitochondrial CYP27A1 0.0804
945 Adrenocorticotropic hormone receptor MC2R 0.0708
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0666
1992 Vitamin D-binding protein GC 0.0578
1566 Corticoliberin CRH 0.0536
66 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II HSD3B2 0.0479
290 Prostaglandin G/H synthase 2 PTGS2 0.0391
1736 Somatostatin SST 0.0311
4186 Neuropeptide Y receptor type 2 NPY2R 0.0311
20 Prostaglandin G/H synthase 1 PTGS1 0.0268
309 Antithrombin-III SERPINC1 0.0251
563 Thyroid peroxidase TPO 0.0238
153 Dopamine beta-hydroxylase DBH 0.0238
275 Arachidonate 5-lipoxygenase ALOX5 0.0215
503 Somatostatin receptor type 1 SSTR1 0.0214
723 Cytosolic phospholipase A2 PLA2G4A 0.021
3866 Serum amyloid A protein SAA1 0.0209
1932 Apolipoprotein E APOE 0.0208
1200 AMBP protein AMBP 0.0208
54 Prothrombin F2 0.0207
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0201
3872 Somatostatin receptor type 5 SSTR5 0.02
6008 Somatostatin receptor type 2 SSTR2 0.02
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.019
6020 Aldehyde oxidase AOX1 0.0188
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0183
239 Coagulation factor X F10 0.0167
4757 Cytochrome P450 2C9 CYP2C9 0.0165
115 Penicillin-binding protein 2 mrdA 0.016
6069 Penicillin-binding protein 2 mrdA 0.016
6118 Penicillin-binding protein 2 penA 0.016
6187 Penicillin-binding protein 2 pbpA 0.016
6686 Penicillin-binding protein 2 pbp2 0.016
6939 Penicillin-binding protein 2 mrdA 0.016
7163 Penicillin-binding protein 2 pbpA 0.016
867 Penicillin-binding protein 3 pbpC 0.016
6119 Penicillin-binding protein 3 pbp3 0.016
7154 Penicillin-binding protein 3 pbp3 0.016
7157 Penicillin-binding protein 3 LMHCC_2184 0.016
7162 Penicillin-binding protein 3 pbpB 0.016
7172 Penicillin-binding protein 3 pbp3 0.016
6012 Tryptophan 2,3-dioxygenase TDO2 0.0155
4200 Cytochrome P450 1A2 CYP1A2 0.0146
6165 Copper-transporting ATPase 1 ATP7A 0.0132
6163 Copper-transporting ATPase 2 ATP7B 0.0132
633 Penicillin-binding proteins 1A/1B pbpA 0.0132
6146 High affinity copper uptake protein 1 SLC31A1 0.0125
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0121
6270 Group IIE secretory phospholipase A2 PLA2G2E 0.0121
908 Glutathione S-transferase theta-1 GSTT1 0.0119
6024 Cytochrome P450 1A1 CYP1A1 0.0119
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0119
896 Glutathione S-transferase Mu 1 GSTM1 0.0105
6016 Cytochrome P450 2C19 CYP2C19 0.0104
118 Organic cation/carnitine transporter 2 SLC22A5 0.0103
3947 Xanthine dehydrogenase/oxidase XDH 0.0099
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0099
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0098
904 Glutathione S-transferase P GSTP1 0.0094
4924 Cytochrome P450 2C8 CYP2C8 0.0089
6030 Cytochrome P450 2B6 CYP2B6 0.0089
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0083
713 Sodium-dependent dopamine transporter SLC6A3 0.008
3941 Amine oxidase [flavin-containing] A MAOA 0.008
238 Peroxisome proliferator-activated receptor gamma PPARG 0.008
3939 Amine oxidase [flavin-containing] B MAOB 0.008
6182 Cytochrome P450 2J2 CYP2J2 0.0079
6013 Cytochrome P450 2E1 CYP2E1 0.0078
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0076
1729 Solute carrier family 22 member 6 SLC22A6 0.0075
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0075
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0071
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0069
109 Mitochondrial carnitine/acylcarnitine carrier protein CACL SLC25A29 0.0067
636 Mitochondrial carnitine/acylcarnitine carrier protein SLC25A20 0.0067
3601 Dihydropteroate synthase 1 folP1 0.0065
3807 Dihydropteroate synthase 1 folP1 0.0065
3808 Dihydropteroate synthase 2 folP2 0.0065
122 P2Y purinoceptor 12 P2RY12 0.0062
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.006
4119 Cytochrome P450 2D6 CYP2D6 0.006
6036 Eosinophil peroxidase EPX 0.0059
6168 Solute carrier family 22 member 16 SLC22A16 0.0058
200 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 0.0058
451 Carnitine O-palmitoyltransferase I, liver isoform CPT1A 0.0058
3830 Calreticulin CALR 0.0057
412 Peroxisomal carnitine O-octanoyltransferase CROT 0.0057
551 Carnitine O-acetyltransferase CRAT 0.0057
6034 Hydroxyindole O-methyltransferase ASMT 0.0055
6035 Nuclear receptor ROR-beta RORB 0.0055
1898 Cytochrome P450 1B1 CYP1B1 0.0053
6142 Solute carrier family 22 member 8 SLC22A8 0.0051
765 Indoleamine 2,3-dioxygenase IDO1 0.0047
6102 Arylamine N-acetyltransferase 2 NAT2 0.0045
362 Melatonin receptor type 1B MTNR1B 0.0045
571 Melatonin receptor type 1A MTNR1A 0.0045
6144 Solute carrier family 22 member 2 SLC22A2 0.0042
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0041
4604 Liver carboxylesterase 1 CES1 0.0037
833 Organic cation/carnitine transporter 1 SLC22A4 0.0035
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0033
6106 Cytochrome P450 2C18 CYP2C18 0.0033
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.003
465 Calmodulin CALM1 0.0029
6147 Solute carrier family 22 member 3 SLC22A3 0.0027
468 Cytochrome P450 4A11 CYP4A11 0.0026
6137 Multidrug resistance-associated protein 6 ABCC6 0.0026
3811 Cytochrome P450 19A1 CYP19A1 0.0026
6107 Cytochrome P450 3A7 CYP3A7 0.0024
136 Estrogen receptor ESR1 0.0024
6136 Multidrug resistance-associated protein 5 ABCC5 0.0024
4118 Cytochrome P450 3A5 CYP3A5 0.0023
6145 Solute carrier family 22 member 1 SLC22A1 0.0023
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0021
3923 Cholinesterase BCHE 0.0018
1588 Multidrug resistance protein 1 ABCB1 0.0013
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