Details of the Drug

General Information of Drug (ID: DM1237M)

Drug Name

Alfacalcidol

Synonyms

Alfacalcidol [INN:BAN:JAN]; Alfacalcidolum; Alfacalcidolum [INN-Latin]; Alfarol; Alpha D 3; Alphacalcidol; Alsiodol; Bondiol; EinsAlpha; One-Alpha; Oxydevit; Sinovul; URQ2517572; Un-Alpha; Vitamin D3, 1alpha-Hydroxy-; alfacalcidol; alpha-Calcidol; (5Z,7E)-9,10-Seco-5,7,10(19)-cholestatrien-1alpha,3beta-diol; 1-Hydroxycholecalciferol; 1-Hydroxyvitamin D3; 1alpha-Hydroxy-vitamin D3; 1alpha-Hydroxycholecalciferol; 1alpha-Hydroxyvitamin D3; 1alpha-OH-D3; 41294-56-8; CCRIS 3341; CHEBI:31186; UNII-URQ2517572

Indication

Disease Entry	ICD 11	Status	REF
Hyperparathyroidism	5A51	Approved	[1]
Hypoparathyroidism	5A50	Approved	[2]
Renal osteodystrophy	N.A.	Approved	[3]
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Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

400.6

Logarithm of the Partition Coefficient (xlogp)

6.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is passively and completely absorbed in the small intestine [4]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
Bioavailability: 71% of drug becomes completely available to its intended biological destination(s) [6]
Clearance: The drug present in the plasma can be removed from the body at the rate of 0.82 mL/min/kg [7]
Elimination: 8% of drug is excreted from urine in the unchanged form [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 48.6 hours [7]
Metabolism: The drug is metabolized via the liver [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00012 micromolar/kg/day [8]

Chemical Identifiers

Formula: C27H44O2
IUPAC Name: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Canonical SMILES: CC(C)CCCC(C)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C
InChI: OFHCOWSQAMBJIW-AVJTYSNKSA-N
InChIKey: 1S/C27H44O2/c1-18(2)8-6-9-19(3)24-13-14-25-21(10-7-15-27(24,25)5)11-12-22-16-23(28)17-26(29)20(22)4/h11-12,18-19,23-26,28-29H,4,6-10,13-17H2,1-3,5H3/b21-11+,22-12-/t19-,23-,24-,25+,26+,27-/m1/s1

Cross-matching ID

PubChem CID: 5282181
ChEBI ID: CHEBI:31186
CAS Number: 41294-56-8
DrugBank ID: DB01436
INTEDE ID: DR0060

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Vitamin D(3) 25-hydroxylase (CYP27A1)	DEBS639	CP27A_HUMAN	Substrate	[9]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[11]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Gene/Protein Processing	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Biotransformations	[13]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Gene/Protein Processing	[14]
Retinoic acid receptor RXR-alpha (RXRA)	OTP1TBDM	RXRA_HUMAN	Protein Interaction/Cellular Processes	[15]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Gene/Protein Processing	[14]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Drug Response	[16]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Gene/Protein Processing	[12]
Vitamin D3 receptor	OTFC7K35	VDR_HUMAN	Gene/Protein Processing	[17]

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Molecular Interaction Atlas (MIA)

MIA Detail

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References

1	X-Linked Hypophosphatemia. 2012 Feb 9 [updated 2023 Dec 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
2	Auditing the Efficacy and Safety of Alfacalcidol and Calcium Therapy in Idiopathic Hypoparathyroidism. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1325-1335.
3	Cross-linked C-terminal telopeptide of type I collagen in serum before and after treatment with alfacalcidol and calcium carbonate in early and moderate chronic renal failure. Nephron. 2002 Oct;92(2):304-8.
4	Summary of Product Characteristics: Alfacalcidol Aristo oral capsules
5	BDDCS applied to over 900 drugs
6	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
7	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9	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.
10	Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56.
11	Dermal fibroblasts pretreated with a sterol Delta7-reductase inhibitor produce 25-hydroxyvitamin D3 upon UVB irradiation. J Photochem Photobiol B. 2006 Oct 2;85(1):72-8.
12	Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia. Blood Purif. 2004;22(2):210-5. doi: 10.1159/000076855.
13	CYP3A4 is a human microsomal vitamin D 25-hydroxylase. J Bone Miner Res. 2004 Apr;19(4):680-8.
14	1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro. Eur J Med Res. 2005 Apr 20;10(4):179-82.
15	Hydrogen/deuterium exchange reveals distinct agonist/partial agonist receptor dynamics within vitamin D receptor/retinoid X receptor heterodimer. Structure. 2010 Oct 13;18(10):1332-41. doi: 10.1016/j.str.2010.07.007.
16	Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis. J Bone Miner Res. 2000 Mar;15(3):415-20. doi: 10.1359/jbmr.2000.15.3.415.
17	Functional evolution of the vitamin D and pregnane X receptors. BMC Evol Biol. 2007 Nov 12;7:222. doi: 10.1186/1471-2148-7-222.