Drug Details

General Information of the Drug (ID: DR3078)
Name
1,25-dihydroxyvitamin D3
Synonyms
calcitriol; Rocaltrol; 32222-06-3; Calcijex; Topitriol; 1alpha,25-Dihydroxyvitamin D3; Silkis; Soltriol; 1alpha,25-Dihydroxycholecalciferol; Calcitriolum; Dihydroxyvitamin D3; 1,25-DHCC; 1,25-Dihydroxyvitamin D; Vectical; 1,25-DIHYDROXYCHOLECALCIFEROL; 1,25-Dihydroxyvitamin D3; 1alpha,25-Dihydroxyvitamin D; 1-alpha,25-Dihydroxyvitamin D3; Calcitriolum [INN-Latin]; UNII-FXC9231JVH; 1alpha,25(OH)2D3; DN-101; 1,25-Dihydroxycholecaliferol; CCRIS 5522; Ro 21-5535; HSDB 3482; 1-alpha,25-Dihydroxycholecalciferol; EINECS 250-963-8; DN 101; Calcitriol (chemotherapy-induced alopecia); Calcitriol (chemotherapy-induced alopecia), Cytotech Labs; Calcitriol (API-31543, drug-induced alopecia), Cytotech Labs; 1alpha,25 dihydroxyvitamin D(3)
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Molecular Type
Small molecule
Disease Congenital alopecia [ICD-11: LC30] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C27H44O3
PubChem CID
5280453
Canonical SMILES
CC(CCCC(C)(C)O)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C
InChI
1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1
InChIKey
GMRQFYUYWCNGIN-NKMMMXOESA-N
CAS Number
CAS 32222-06-3
TTD Drug ID
D0T2PL
DrugBank ID
DB15557
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Low-dose 1,25-dihydroxyvitamin D3 combined with arsenic trioxide synergistically inhibits proliferation of acute myeloid leukemia cells by promoting apoptosis.
          Beta carotene      Daucus carota     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model EC9706 CVCL_E307 Esophageal squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 These two agents in combination synergistically inhibited cell growth and induced apoptosis.
          Bufalin      Bufo gargarizans     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CYP24A1  Molecule Info 
Pathway MAP
Up-regulation Expression VDR  Molecule Info 
Pathway MAP
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Bufalin in combination with 1,25(OH)(2)D(3) enhanced the expression of VDR target genes, such as CYP24A1 and cathelicidin antimicrobial peptide, and effectively induced differentiation phenotypes.
          Carnosic acid      Salvia rosmarinus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Phosphorylation c-RAF  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation MEK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RSK1  Molecule Info 
Pathway MAP
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha,25-dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CYP24A1  Molecule Info 
Pathway MAP
Down-regulation Expression CYP27B1  Molecule Info 
Pathway MAP
Up-regulation Expression GPX1  Molecule Info 
Pathway MAP
Down-regulation Expression ITGB3  Molecule Info 
Pathway MAP
                    In-vitro Model MBCDF Breast cancer Homo sapiens
                    Experimental
                    Result(s)		 The concomitant administration of calcitriol with curcumin synergistically promoted anticancer effects in vitro and in vivo.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CYP24A1  Molecule Info 
Pathway MAP
Up-regulation Expression VDR  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Genistein potentiates the antiproliferative actions of 1,25(OH)2D3 in DU145 cells by two mechanisms: (i) an increase in the half-life of 1,25(OH)2D3 due to the direct inhibition of CYP24 enzyme activity and (ii) an amplification of the homologous up-regulation of VDR.
          Yomogin + Tretinoin     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Yomogin may be useful in combination with 1,25-(OH)(2) D(3) or all- trans-RA in the differentiation therapy for myeloid leukemias.
    β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Silibinin      Carduus marianus     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression SNAI1  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI2  Molecule Info 
Pathway MAP
Up-regulation Expression VDR  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
SW480R CVCL_AT68 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Silibinin restored 1,25D responsiveness in vitamin D-resistant colon cancer cells by downregulation of Snail1 and Snail2 and upregulation of vitamin D receptor.
Target and Pathway
Target(s) Vitamin D3 receptor (VDR)  Molecule Info  [10]
KEGG Pathway Endocrine and other factor-regulated calcium reabsorption Click to Show/Hide
2 Mineral absorption
3 Tuberculosis
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
Panther Pathway Vitamin D metabolism and pathway Click to Show/Hide
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Direct p53 effectors
3 RXR and RAR heterodimerization with other nuclear receptor
4 Retinoic acid receptors-mediated signaling
5 Validated transcriptional targets of deltaNp63 isoforms
6 Validated transcriptional targets of TAp63 isoforms
Reactome Nuclear Receptor transcription pathway Click to Show/Hide
WikiPathways Ovarian Infertility Genes Click to Show/Hide
2 Nuclear Receptors in Lipid Metabolism and Toxicity
3 Nuclear Receptors Meta-Pathway
4 Vitamin D Receptor Pathway
5 Drug Induction of Bile Acid Pathway
6 Nuclear Receptors
7 Vitamin D Metabolism
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2779).
Reference 2 Low-dose 1,25-dihydroxyvitamin D(3) combined with arsenic trioxide synergistically inhibits proliferation of acute myeloid leukemia cells by promoting apoptosis. Oncol Rep. 2013 Jul;30(1):485-91.
Reference 3 Inhibition of proliferation and induction of apoptosis by the combination of Beta-carotene and 1,25-dihydroxyvitamin D3 in human esophageal cancer EC9706 cells. Asian Pac J Cancer Prev. 2012;13(12):6327-32.
Reference 4 Increased nuclear expression and transactivation of vitamin D receptor by the cardiotonic steroid bufalin in human myeloid leukemia cells. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):144-51.
Reference 5 Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha,25-dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium. Cancer Res. 2003 Mar 15;63(6):1325-32.
Reference 6 Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts. Cancers (Basel). 2019 Nov 6;11(11):1739.
Reference 7 Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: role of the direct inhibition of CYP24 enzyme activity. Mol Cell Endocrinol. 2005 Sep 28;241(1-2):49-61.
Reference 8 Restoration of the anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells. Cancer Lett. 2015 Jul 1;362(2):199-207.
Reference 9 Synergistic induction of 1,25-dihydroxyvitamin D(3)- and all-trans-retinoic acid-induced differentiation of HL-60 leukemia cells by yomogin, a sesquiterpene lactone from Artemisia princeps. Planta Med. 2002 Oct;68(10):886-90.
Reference 10 Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94.
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