CALCIFEDIOL ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H44O2
Molecular Weight	400.6371
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3\C[C@@H](O)CCC3=C)[C@H](C)CCCC(C)(C)O

InChI

InChIKey=JWUBBDSIWDLEOM-DTOXIADCSA-N

InChI=1S/C27H44O2/c1-19-10-13-23(28)18-22(19)12-11-21-9-7-17-27(5)24(14-15-25(21)27)20(2)8-6-16-26(3,4)29/h11-12,20,23-25,28-29H,1,6-10,13-18H2,2-5H3/b21-11+,22-12-/t20-,23+,24-,25+,27-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/4310770

Calcifediol (25-Hydroxyvitamin D3 or 25-hydroxycholecalciferol) is a biologically active vitamin D3 metabolite. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D3 into calcifediol. Calcifediol is a prohormone of the active form of vitamin D3, calcitriol (1,25-dihydroxyvitamin D3). Calcifediol is converted to calcitriol by cytochrome P450 27B1 (CYP27B1), also called 1-alpha hydroxylase, primarily in the kidney. Calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis. RAYALDEE (calcifediol) extended-release capsules is indicated for the treatment of secondary hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19944755	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208010s000lbl.pdf	Primary	Approved 8429	RAYALDEE Approved Use Calcifediol indicated for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL Launch Date 2016
Hypocalcemia, chronic 3 Sources: https://www.drugs.com/mmx/calderol.html	Primary	Approved 8429	CALDEROL Approved Use Unknown Launch Date 1980
Hypophosphatemia 30 Sources: https://www.drugs.com/mmx/calderol.html	Primary	Approved 8429	CALDEROL Approved Use Unknown Launch Date 1980
Osteodystrophy 3 Sources: https://www.drugs.com/mmx/calderol.html	Primary	Approved 8429	CALDEROL Approved Use Unknown Launch Date 1980

C_max

Value	Dose	Co-administered	Analyte	Population
73.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24516879/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CALCIFEDIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1704.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24516879/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CALCIFEDIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24516879/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CALCIFEDIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24516879/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CALCIFEDIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED

Doses

Dose	Population	Adverse events
30 ug 1 times / day multiple, oral (starting) Dose: 30 ug, 1 times / day Route: oral Route: multiple Dose: 30 ug, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208010s000lbl.pdf	unhealthy, 66 years (range: 25-85 years) n = 285 Health Status: unhealthy Condition: secondary hyperparathyroidism Age Group: 66 years (range: 25-85 years) Sex: M+F Population Size: 285 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208010s000lbl.pdf	Other AEs: Anemia, Nasopharyngitis... Other AEs: Anemia (4.9%) Nasopharyngitis (4.9%) Blood creatinine increased (4.9%) Dyspnea (4.2%) Cough (3.5%) Cardiac failure congestive (3.5%) Constipation (3.2%) Bronchitis (2.8%) Hyperkalemia (2.5%) Osteoarthritis (2.1%) Hyperuricemia (1.8%) Contusion (1.8%) Pneumonia (1.4%) Chronic obstructive pulmonary disease (1.4%) Calcium increased serum (4.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208010s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP27B1 3 UGT enzymes 27

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208010Orig1s000ClinPharmR.pdf Page: 9.0	likely
CYP27B1 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208010Orig1s000PharmR.pdf Page: 31.0	yes

Sourcing

Vendor/Aggregator	ID	URL
AHH Chemical co.,ltd	MT-48884	http://www.ahhchemical.com/product/MT-48884.html
Achemtek	0102-017034	http://www.achemtek.com/19356-17-3
ApexBio Technology	B2140	http://www.apexbt.com/calcifediol-26843.html
ApexBio Technology	B1056	http://www.apexbt.com/calcifediol-d6.html
Aurora Fine Chemicals LLC	A17.876.862	http://online.aurorafinechemicals.com/info?ID=A17.876.862
Aurum Pharmatech LLC	W-5159	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5159
AvaChem Scientific	2558	http://www.avachem.com/productSearch.asp?2558
BioCrick	BCC4949	http://www.biocrick.com/Calcifediol-BCC4949.html
BioSynth	W-201718	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-201718.html
Boerchem	BC219279	http://www.boerchem.com/?product_36973.html
Capot Chemical	18824	http://www.capotchem.com/en/18824.htm
Capot Chemical	PubChem18824	http://www.capotchem.com/en/18824.htm
Chem Scene	CS-0800	http://www.chemscene.com/19356-17-3.html
ChemFaces	CFN94017	http://www.chemfaces.com/natural/25-Hydroxycholecalciferol-monohydrate-CFN94017.html
ChemMol	44005951	http://www.chemmol.com/chemmol/44005951.html
Chemspace	CSSB00032005042	https://chem-space.com/CSSB00032005042
Chiralblock Biosciences	CB11410	http://www.chiralblock.com/products/63283-36-3.html
EMD Biosciences	679102	http://www.emdbiosciences.com/product/679102
EMD Millipore	679102	http://www.emdbiosciences.com/product/679102
Glentham Life Sciences	GV7732	http://www.glentham.com/products/product/GV7732/
Lab Network	LN00197433	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00197433
MedChem Express	HY-32351	https://www.medchemexpress.com/Calcifediol.html
MuseChem	R028208	https://www.musechem.com/product/R028208.html
OChem	8414	http://www.ocheminc.com/index.php?act=psearch&pid=356C173
Parchem	28428	http://www.parchem.com/chemical-supplier-distributor/Calcifediol-018428.aspx
Selleck Chemicals	S1469	http://www.selleckchem.com/products/Calcifediol.html
Sigma-Aldrich	739642_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/739642?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	739650_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/739650?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	739669_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/739669?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	17938_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/17938?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1086108_USP	https://www.sigmaaldrich.com/catalog/product/usp/1086108?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Tocris	4036	https://www.tocris.com/products/calcifediol_4036
VladaChem	VL273145-10MG	https://www.vladachem.com/product.php?products=19356-17-3
Yuhao Chemical	XJ4467	http://www.chemyuhao.com/19356-17-3.html
abcr GmbH	AB503647	http://www.abcr.com/shop/en/AB503647
abcr GmbH	AB443287	http://www.abcr.de/shop/en/AB443287
eNovation Chemicals	D699759	https://www.enovationchem.com/ProductDetails.asp?ProductID=D699759
eNovation Chemicals	D763693	https://www.enovationchem.com/ProductDetails.asp?ProductID=D763693
eNovation Chemicals	Y0974281	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974281
iChemical	EBD2201904	http://www.ichemical.com/products/19356-17-3.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Determination of vitamin D and its metabolites in plasma from normal and anephric man.	1979 Jul 15	227368
Interrelationship of serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D in juvenile renal osteodystrophy after therapy with 25-hydroxyvitamin D3.	1982	6897822
Tubular aggregates in a case of osteomalacic myopathy due to anticonvulsant drugs.	1984 Jan-Feb	6705322
Hypercalcemia in 25 OH D3 treated patients receiving a calcium exchange resin.	1985 Jun	4018932
The effect of vitamin D status on cutaneous sterologenesis in vivo and in vitro.	1987 Sep 14	3040120
Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3.	1990 Nov	2127346
1 alpha,25-dihydroxyvitamin D3 inhibits productive infection of human monocytes by HIV-1.	1991 Apr 30	1673842
Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages.	1993 Feb	8383166
Proteins in the heat shock-70 family specifically bind 25-hydroxyvitamin D3 and 17beta-estradiol.	1998 Apr	9543154
A pilot study to assess the safety and efficacy of topical calcipotriol treatment in childhood psoriasis.	1999 Jul-Aug	10469423
Kidney microsomal 25- and 1alpha-hydroxylase in vitamin D metabolism: catalytic properties, molecular cloning, cellular localization and expression during development.	2002 Feb 28	11880238
De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase.	2003 Sep 26	12867411
Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients.	2004	15384827
Overview of general physiologic features and functions of vitamin D.	2004 Dec	15585789
Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.	2005 Aug 1	16061850
Retinoic acid via RARalpha inhibits the expression of 24-hydroxylase in human prostate stromal cells.	2005 Dec 30	16289102
Androgen enhances the antiproliferative activity of vitamin D3 by suppressing 24-hydroxylase expression in LNCaP cells.	2006 Apr	16524720
Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.	2006 Jul-Aug	16886665
Functional evolution of the vitamin D and pregnane X receptors.	2007 Nov 12	17997857
Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile.	2010 Mar 30	20079722
The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species.	2011 Feb 3	21291553

Patents

Sample Use Guides

In Vivo Use Guide

The initial dose of RAYALDEE (calcifediol) extended-release capsules is 30 mcg administered orally once daily at bedtime. Serum calcium should be below 9.8 mg/dL before initiating treatment. Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and intact parathyroid hormone (PTH) 3 months after starting therapy or changing dose. Increase the dose to 60 mcg once daily after 3 months if intact PTH is above the treatment goal. Ensure serum calcium is below 9.8 mg/dL, phosphorus is below 5.5 mg/dL and 25-hydroxyvitamin D is below 100 ng/mL before increasing the dose. Suspend dosing if intact PTH is persistently abnormally low, serum calcium is consistently above the normal range or serum 25 hydroxyvitamin D is consistently above 100 ng/mL

Route of Administration: Oral

In Vitro Use Guide

Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory monocyte-derived macrophages, and only when used at high doses (>100 nM for Calcifediol).

Name

Type

Language

CALCIFEDIOL ANHYDROUS

Common Name

English

CALCIDIOL

Common Name

English

CALCIFEDIOL, ANHYDROUS

Common Name

English

CALCIFEDIOL,ANHYDROUS

Common Name

English

CALCIFEDIOL [MI]

Common Name

English

calcifediol [INN]

Common Name

English

CALCIFEDIOL,ANHYDROUS [VANDF]

Common Name

English

Classification Tree Code System Code

LOINC

83071-1