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], [2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

412.6

Topological Polar Surface Area (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 [3]
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) [4]

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	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Vitamin D(3) 25-hydroxylase (CYP27A1)_{Main DME}	DEBS639	CP27A_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

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)

MEA Detail

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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]	[18]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Doxercalciferol caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[19]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Doxercalciferol caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[20]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Doxercalciferol caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[21]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Doxercalciferol caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[22]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Doxercalciferol caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[23]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Doxercalciferol caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[24]
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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
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⏷ 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	Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5	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.
6	Chemoprevention of prostate cancer by cholecalciferol (vitamin D3): 25-hydroxylase (CYP27A1) in human prostate epithelial cells. Clin Exp Metastasis. 2005;22(3):265-73.
7	Kidney microsomal 25- and 1alpha-hydroxylase in vitamin D metabolism: catalytic properties, molecular cloning, cellular localization and expression during development. Biochim Biophys Acta. 2002 Feb 28;1580(2-3):133-44.
8	Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos. 2006 Apr;34(4):513-20.
9	Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41.
10	Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94.
11	Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr;9(4):345-59.
12	Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3. Bioorg Med Chem. 2000 Aug;8(8):2157-66.
13	In vivo metabolism of the vitamin D analog, dihydrotachysterol. Evidence for formation of 1 alpha,25- and 1 beta,25-dihydroxy-dihydrotachysterol metabolites and studies of their biological activity. J Biol Chem. 1993 Jan 5;268(1):282-92.
14	[Vitamin D2 or vitamin D3]. Rev Med Interne. 2008 Oct;29(10):815-20.
15	New acquisitions in therapy of secondary hyperparathyroidism in chronic kidney disease and peritoneal dialysis patients: role of vitamin D receptor... Contrib Nephrol. 2009;163:219-226.
16	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
17	Evidence for tissue- and cell-type selective activation of the vitamin D receptor by Ro-26-9228, a noncalcemic analog of vitamin D3. J Cell Biochem. 2003 Feb 1;88(2):267-73.
18	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
19	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
20	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
21	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
22	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
23	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
24	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.