25-HYDROXYCHOLECALCIFEROL, 5-TRANS-

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 of 25-HYDROXYCHOLECALCIFEROL, 5-TRANS-

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-WIFPIRAHSA-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
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
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
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
Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.	2006 Jul-Aug	16886665

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

25-HYDROXYCHOLECALCIFEROL, 5-TRANS-

Common Name

English

9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-3,25-DIOL, (3.BETA.,5E,7E)-

Common Name

English

CALCIFEDIOL MONOHYDRATE IMPURITY D [EP IMPURITY]

Common Name

English

(3S,5E,7E)-9,10-secocholesta-5,7,10(19)-triene-3,25-diol

Systematic Name

English

5,6-TRANS-25-HYDROXY VITAMIN D3

Common Name

English

25-HYDROXY-5,6-TRANS-CHOLECALCIFEROL

Common Name

English

Code System Code Type Description

FDA UNII

SN331791VY