Details of the Drug

General Information of Drug (ID: DM6FG1P)

Drug Name
Doxercalciferol
Synonyms
Doxcercalciferol; Hectorol; Doxercalciferol [INN]; TSA 840; BCI-101; Doxercalciferol (INN); Hectorol (TN); (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; (5Z,7E,22E)-9,10-Secoergosta-5,7,10(19),22-tetraene-1alpha,3beta-diol; 1-Hydroxyergocalciferol; 1-alpha-Hydroxyvitamin D2; 1alpha-Hydroxyergocalciferol; 1alpha-OH-D2; 9,10-Secoergosta-5,7,10(19),22-tetraene-1,3-diol,(1-alpha,3-beta,5Z,7E,22E)
Indication
Disease Entry ICD 11 Status REF
Chronic kidney disease GB61 Approved [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 412.6
Logarithm of the Partition Coefficient (xlogp) 6.3
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 32 - 37 hours [2]
Metabolism
The drug is metabolized via the CYP27 in the liver to form 1,25-(OH)2D2 (major metabolite) and 1,24-dihydroxyvitamin D2 (minor metabolite) []
Chemical Identifiers
Formula
C28H44O2
IUPAC Name
(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
Canonical SMILES
C[C@H](/C=C/[C@H](C)C(C)C)[C@H]1CC[C@@H]\\2[C@@]1(CCC/C2=C\\C=C/3\\C[C@H](C[C@@H](C3=C)O)O)C
InChI
InChI=1S/C28H44O2/c1-18(2)19(3)9-10-20(4)25-13-14-26-22(8-7-15-28(25,26)6)11-12-23-16-24(29)17-27(30)21(23)5/h9-12,18-20,24-27,29-30H,5,7-8,13-17H2,1-4,6H3/b10-9+,22-11+,23-12-/t19-,20+,24+,25+,26-,27-,28+/m0/s1
InChIKey
HKXBNHCUPKIYDM-CGMHZMFXSA-N
Cross-matching ID
PubChem CID
5281107
ChEBI ID
CHEBI:4712
CAS Number
54573-75-0
DrugBank ID
DB06410
TTD ID
D0G5CF
INTEDE ID
DR1757
ACDINA ID
D00214

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Vitamin D3 receptor (VDR) TTK59TV VDR_HUMAN Antagonist [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Vitamin D(3) 25-hydroxylase (CYP27A1)
Main DME 		DEBS639 CP27A_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [5]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Post-Translational Modifications [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Post-Translational Modifications [5]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Biotransformations [6]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Chronic kidney disease
ICD Disease Classification GB61
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Vitamin D3 receptor (VDR) DTT VDR 1.69E-02 -0.23 -0.66
Vitamin D(3) 25-hydroxylase (CYP27A1) DME CYP27A1 2.63E-08 -1.47E+00 -1.99E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Doxercalciferol (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Pexidartinib DMS2J0Z Moderate Increased metabolism of Doxercalciferol caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [7]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Doxercalciferol caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [8]
PF-06463922 DMKM7EW Moderate Increased metabolism of Doxercalciferol caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [9]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Doxercalciferol caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [10]
Abametapir DM2RX0I Moderate Decreased metabolism of Doxercalciferol caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [11]
Lefamulin DME6G97 Moderate Decreased metabolism of Doxercalciferol caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [12]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Doxercalciferol caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [13]
⏷ Show the Full List of 7 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Allura red AC dye E00338 33258 Colorant
Isopropyl alcohol E00070 3776 Antimicrobial preservative; Solvent
Quinoline yellow WS E00309 24671 Colorant
Sunset yellow FCF E00255 17730 Colorant
Ammonia E00007 222 Alkalizing agent
Butyl alcohol E00011 263 Flavoring agent; Solvent
Butylhydroxyanisole E00308 24667 Antimicrobial preservative; Antioxidant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Glycerin E00026 753 Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Medium-chain triglyceride E00640 Not Available Emollient; Lubricant; Surfactant
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Water E00035 962 Solvent
⏷ Show the Full List of 14 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Doxercalciferol 0.0005 mg capsule 0.0005 mg Oral Capsule Oral
Doxercalciferol 0.001 mg capsule 0.001 mg Oral Capsule Oral
Doxercalciferol 0.0025 mg capsule 0.0025 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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: 2790).
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
4 Efficacy and safety of oral doxercalciferol in the management of secondary hyperparathyroidism in chronic kidney disease stage 4. Indian J Nephrol. 2013 Jul;23(4):271-5.
5 KML001 and doxercalciferol induce synergistic antileukemic effect in acute lymphoid leukemia cells. Oncol Rep. 2017 Jul;38(1):481-487. doi: 10.3892/or.2017.5688. Epub 2017 Jun 1.
6 CYP3A4 is a human microsomal vitamin D 25-hydroxylase. J Bone Miner Res. 2004 Apr;19(4):680-8.
7 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
8 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
9 Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
10 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
11 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
12 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
13 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.