Vitamin D3
Explore a selection of our essential drug information below, or:
Identification
- Summary
Vitamin D3 is a form of Vitamin D used in the treatment of specific medical conditions such as refractory rickets, hypoparathyroidism, and familial hypophosphatemia, as well as osteoporosis and chronic kidney disease.
- Brand Names
- Adrovance, Animi-3 With Vitamin D, Citranatal B-calm Kit, Citranatal Harmony, Fosamax Plus D, Fosavance, Infuvite, Infuvite Pediatric, Mvc-fluoride, Natafort, Pregvit, Vidextra
- Generic Name
- Cholecalciferol
Commonly known or available as Vitamin D3 - DrugBank Accession Number
- DB00169
- Background
Vitamin D, in general, is a secosteroid generated in the skin when 7-dehydrocholesterol located there interacts with ultraviolet irradiation - like that commonly found in sunlight 9. Both the endogenous form of vitamin D (that results from 7-dehydrocholesterol transformation), vitamin D3 (cholecalciferol), and the plant-derived form, vitamin D2 (ergocalciferol), are considered the main forms of vitamin d and are found in various types of food for daily intake 9. Structurally, ergocalciferol differs from cholecalciferol in that it possesses a double bond between C22 and C23 and has an additional methyl group at C24 9. Finally, ergocalciferol is pharmacologically less potent than cholecalciferol, which makes vitamin D3 the preferred agent for medical use 9.
Appropriate levels of vitamin D must be upheld in the body in order to maintain calcium and phosphorus levels in a healthy physiologic range to sustain a variety of metabolic functions, transcription regulation, and bone metabolism 4,9,10,11,12,13,14. However, studies are also ongoing to determine whether or not cholecalciferol may also play certain roles in cancer, autoimmune disorders, cardiovascular disease, and other medical conditions that may be associated with vitamin D deficiency 9.
- Type
- Small Molecule
- Groups
- Approved, Nutraceutical
- Structure
- Weight
- Average: 384.6377
Monoisotopic: 384.33921603 - Chemical Formula
- C27H44O
- Synonyms
- (+)-vitamin D3
- (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol
- (5Z,7E)-(3S)-9,10-secocholesta-5,7,10(19)-trien-3-ol
- Activated 7-dehydrocholesterol
- Calciol
- CC
- Cholecalciferol
- Cholecalciferolum
- Colecalciferol
- Colecalciferolum
- Oleovitamin D3
- Vitamin D-3
- Vitamin D3
- External IDs
- NSC-375571
Pharmacology
- Indication
Cholecalciferol use is indicated for the treatment of specific medical conditions like refractory rickets (or vitamin D resistant rickets), hypoparathyroidism, and familial hypophosphatemia 12,13.
Concurrently, as one of the most commonly utilized forms of vitamin D, cholecalciferol is also very frequently used as a supplement in individuals to maintain sufficient vitamin d levels in the body or to treat vitamin D deficiency, as well as various medical conditions that can be associated directly or indirectly with vitamin d insufficiency like osteoporosis and chronic kidney disease, among others 2,3,15.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Calcium and vitamin d deficiencies Combination Product in combination with: Calcium carbonate (DB06724) •••••••••••• •••••• ••••••• Used in combination to prevent Deficiency, vitamin a Combination Product in combination with: Vitamin A (DB00162) •••••••••••• •••••••••• •••••••• Used in combination to treat Deficiency, vitamin a Combination Product in combination with: Vitamin A (DB00162) •••••••••••• •••••••••• •••••••• Used in combination to treat Deficiency, vitamin a Combination Product in combination with: Vitamin A (DB00162) •••••••••••• •••••••• • ••••• Used in combination to treat Deficiency, vitamin d Combination Product in combination with: Vitamin A (DB00162) •••••••••••• •••••••• • ••••• - Associated Therapies
- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D 12,13,14. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization 12,13,14. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules 12,13,14. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys 12,13,14. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys 12,13,14.
- Mechanism of action
Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight 9,12,13,14.
Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease 1. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone 4. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus 4. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions 4.
Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet 4. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation 4,1. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma 4,1.
In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively 9. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts 9. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels 9. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys 9.
Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements 9. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome 9. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency 9. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions 9.
Target Actions Organism AVitamin D3 receptor agonistHumans - Absorption
Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal 12,13,14. Moreover, bile is necessary for absorption as well 12,13,14.
In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol 7.
- Volume of distribution
Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L 5.
- Protein binding
The protein binding documented for cholecalciferol is 50 to 80% 8. Specifically, in the plasma, vitamin D3 (from either diet or the skin) is bound to vitamin D-binding protein (DBP) produced in the liver, for transport to the liver. Ultimately, the form of vitamin D3 reaching the liver is 25-hydroxylated, and such 25-hydroxycholecalciferol is bound to DBP (α2-globulin) whilst circulating in the plasma 14.
- Metabolism
Within the liver, cholecalciferol is hydroxylated to calcifediol (25-hydroxycholecalciferol) by the enzyme vitamin D-25-hydroxylase 12,13,14. At the kidney, calcifediol subsequently serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3 12,13,14.
Hover over products below to view reaction partners
- Route of elimination
It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces 8.
- Half-life
At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days 8 while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days 10.
Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals 6.
- Clearance
Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day 5.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae 12,13,14. Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia 12,13,14. Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures 12,13,14.
Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established 12,13,14. Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus, and other effects 12,13,14. Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures 12,13,14.
Vitamin D is deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of Vitamin D3 in excess of 10 µg daily should not be administered daily to nursing women.
- Pathways
Pathway Category Lovastatin Action Pathway Drug action Cerivastatin Action Pathway Drug action Hypercholesterolemia Disease Chondrodysplasia Punctata II, X-Linked Dominant (CDPX2) Disease Smith-Lemli-Opitz Syndrome (SLOS) Disease Mevalonic Aciduria Disease Simvastatin Action Pathway Drug action Pravastatin Action Pathway Drug action Rosuvastatin Action Pathway Drug action Zoledronate Action Pathway Drug action Pamidronate Action Pathway Drug action Fluvastatin Action Pathway Drug action Lysosomal Acid Lipase Deficiency (Wolman Disease) Disease Cholesteryl Ester Storage Disease Disease Steroid Biosynthesis Metabolic Ibandronate Action Pathway Drug action Alendronate Action Pathway Drug action Risedronate Action Pathway Drug action Atorvastatin Action Pathway Drug action Desmosterolosis Disease CHILD Syndrome Disease Hyper-IgD Syndrome Disease Wolman Disease Disease - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Cholecalciferol can be increased when it is combined with Abametapir. Acebutolol The metabolism of Acebutolol can be decreased when combined with Cholecalciferol. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Cholecalciferol. Acetyldigitoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Cholecalciferol is combined with Acetyldigitoxin. Alfacalcidol The risk or severity of adverse effects can be increased when Cholecalciferol is combined with Alfacalcidol. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Delta-D / Micro-D / Optimal-D (RV Nutritional, LLC) / Vigantol
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image D-tabs Tablet 10000 unit Oral Laboratoire Riva Inc. 1992-12-31 Not applicable Canada Luxa-D Capsule 5000 unit Oral Orimed Pharma Corporation 2015-10-20 Not applicable Canada Luxa-D Capsule 50000 unit Oral Orimed Pharma Corporation 2015-10-20 Not applicable Canada Luxa-D Capsule 10000 unit Oral Orimed Pharma Corporation 2015-10-20 Not applicable Canada Luxa-D Capsule 25000 unit Oral Orimed Pharma Corporation 2015-07-31 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ag-vitamine D Capsule 10000 unit Oral Angita Pharma Inc. Not applicable Not applicable Canada Ag-vitamine D Tablets Tablet 10000 unit Oral Angita Pharma Inc. 2020-12-21 Not applicable Canada Euro D 10 000 Capsule 10000 unit Oral Euro Pharm International Canada Inc 2017-08-16 Not applicable Canada Euro-D 10000 Iu Capsule 10000 unit Oral Euro Pharm International Canada Inc 2011-08-29 Not applicable Canada Euro-D 5000 Iu Capsule 5000 unit Oral Euro Pharm International Canada Inc Not applicable Not applicable Canada - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image BLACKMORES VITAMIN D3 1000IU CAPSULES Capsule 1000 IU Oral BLACKMORES (MALAYSIA) SDN. BHD. 2020-09-08 Not applicable Malaysia D Caps 400 Units Capsule 400 unit Oral Twin Laboratories Inc. 1995-12-31 1999-11-10 Canada D Vi Sol Infants Drops 400unit/0.6ml Solution / drops 400 unit / .6 mL Oral Mead Johnson Nutritionals 1985-12-31 1998-09-28 Canada GNC Vitamin D-3 400 Tablet 400 IU Oral GNC LIVEWELL MALAYSIA SDN. BHD. 2020-09-08 Not applicable Malaysia Growth Supportpatch, Hautuki Patch 0.2 mg/100g Topical CUSTICS 2023-05-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 21st Century Maxi Cal Tablet Cholecalciferol (200 IU) + Calcium (600 mg) Tablet Oral 21ST CENTURY PRODUCTS SDN. BHD. 2020-09-08 Not applicable Malaysia 24 Multivitamins + Minerals Cholecalciferol (400 unit) + Ascorbic acid (150 mg) + Beta carotene (10000 unit) + Biotin (25 mcg) + Calcium (130 mg) + Choline bitartrate (25 mg) + Chromium (20 mcg) + Copper (1 mg) + Cyanocobalamin (25 mcg) + Ferrous fumarate (15 mg) + Folic acid (.8 mg) + Inositol (25 mg) + Magnesium (65 mg) + Manganese cation (2 mg) + Molybdenum (20 mcg) + Niacin (25 mg) + Calcium pantothenate (25 mg) + Potassium (15 mg) + Potassium Iodide (.1 mg) + Pyridoxine hydrochloride (25 mg) + Racemethionine (25 mg) + Riboflavin (25 mg) + Selenium (20 mcg) + Thiamine hydrochloride (25 mg) + Vanadium (20 mcg) + Vitamin A palmitate (5000 unit) + Vitamin E (50 unit) + Zinc (10 mg) Tablet Oral Stanley Pharmaceuticals, A Division Of Vita Health Products Inc. 1997-04-30 2002-07-31 Canada 50 Plus Multiple Vitamins & Minerals Cholecalciferol (400 unit) + Ascorbic acid (90 mg) + Biotin (45 mcg) + Calcium (200 mg) + Chromium (10 mcg) + Copper (2 mg) + Cyanocobalamin (25 mcg) + Folic acid (0.4 mg) + Magnesium (100 mg) + Manganese cation (5 mg) + Molybdenum (25 mcg) + Nicotinamide (40 mg) + Pantothenic acid (10 mg) + Potassium Iodide (0.15 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin (3.2 mg) + Selenium (25 mcg) + Thiamine mononitrate (2.25 mg) + Vanadium (10 mcg) + Vitamin A palmitate (6000 unit) + Zinc (15 mg) Tablet Oral Gfr Pharma Ltd. 2002-10-20 2004-06-15 Canada A + D Ointment Cholecalciferol (500 unit / g) + Vitamin A palmitate (2000 unit / g) Ointment Topical National Care Products Ltd. 1993-12-31 2002-10-10 Canada A.R.T.H. Away Formula Cholecalciferol (45 unit) + Calcium (24 mg) + Copper (0.232 mg) + Folic acid (0.025 mg) + Manganese cation (0.58 mg) + Pyridoxine hydrochloride (0.5 mg) + Selenium (1.54 mcg) + Zinc (0.63 mg) Capsule Oral Abundance Naturally Ltd 1999-02-01 2006-06-16 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Abavite Cholecalciferol (0.025 mg/1) + Ascorbic acid (60 mg/1) + DL-alpha tocopheryl acetate (13.5 mg/1) + Ferrous sulfate (30 mg/1) + Folic acid (1 mg/1) + Magnesium oxide (25 mg/1) + Mecobalamin (0.5 mg/1) + Niacin (15 mg/1) + Calcium pantothenate (5 mg/1) + Potassium Iodide (0.25 mg/1) + Riboflavin (1.8 mg/1) + Thiamine mononitrate (1.6 mg/1) + Vitamin A palmitate (0.33 mg/1) + Zinc oxide (15 mg/1) Tablet Oral ABACOS HEALTH 2021-03-31 Not applicable US Active FE Cholecalciferol (400 [iU]/1) + Ascorbic acid (160 mg/1) + Beta carotene (2100 [iU]/1) + Cupric oxide (1 mg/1) + Cyanocobalamin (30 ug/1) + DL-alpha tocopheryl acetate (40 [iU]/1) + Folic acid (1250 ug/1) + Iron (75 mg/1) + Magnesium oxide (30 mg/1) + Nicotinamide (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (4 mg/1) + Thiamine hydrochloride (4 mg/1) + Zinc oxide (20 mg/1) Tablet Oral GM Pharmaceuticals, INC 2013-11-11 Not applicable US Active OB Cholecalciferol (400 [iU]/1) + Ascorbic acid (100 mg/1) + Cupric sulfate pentahydrate (2 mg/1) + Cyanocobalamin (30 ug/1) + D-alpha-Tocopherol acetate (30 [iU]/1) + Doconexent (320 mg/1) + Folic acid (1 mg/1) + Iron (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (4 mg/1) + Thiamine mononitrate (2 mg/1) + Zinc oxide (30 mg/1) Capsule, liquid filled Oral GM Pharmaceuticals, INC 2013-10-28 2017-03-31 US Animi-3 Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Folic acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1) Capsule Oral Pbm Pharmaceuticals Inc. 2011-06-01 Not applicable US Animi-3 with Vitamin D Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Folic acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1) Capsule Oral Pbm Pharmaceuticals Inc. 2011-06-01 Not applicable US
Categories
- ATC Codes
- M05BB09 — Ibandronic acid and colecalciferol
- M05BB — Bisphosphonates, combinations
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- M05BX — Other drugs affecting bone structure and mineralization
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- M05BB — Bisphosphonates, combinations
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- M05BB — Bisphosphonates, combinations
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- A11CC — Vitamin D and analogues
- A11C — VITAMIN A AND D, INCL. COMBINATIONS OF THE TWO
- A11 — VITAMINS
- A — ALIMENTARY TRACT AND METABOLISM
- M05BB — Bisphosphonates, combinations
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- A11CC — Vitamin D and analogues
- A11C — VITAMIN A AND D, INCL. COMBINATIONS OF THE TWO
- A11 — VITAMINS
- A — ALIMENTARY TRACT AND METABOLISM
- M05BB — Bisphosphonates, combinations
- M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
- M05 — DRUGS FOR TREATMENT OF BONE DISEASES
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Alimentary Tract and Metabolism
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Cholecalciferol, antagonists & inhibitors
- Cholestanes
- Cholestenes
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Diet, Food, and Nutrition
- Drugs Affecting Bone Structure and Mineralization
- Drugs for Treatment of Bone Diseases
- Food
- Fused-Ring Compounds
- Growth Substances
- Lipids
- Membrane Lipids
- Micronutrients
- Musculo-Skeletal System
- Physiological Phenomena
- Secosteroids
- Steroids
- Sterols
- Vitamin D and Analogues
- Vitamins
- Vitamins (Fat Soluble)
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as vitamin d and derivatives. These are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Vitamin D and derivatives
- Direct Parent
- Vitamin D and derivatives
- Alternative Parents
- Triterpenoids / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
- Substituents
- Alcohol / Aliphatic homopolycyclic compound / Cyclic alcohol / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound / Secondary alcohol / Triterpenoid
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- secondary alcohol, steroid hormone, seco-cholestane, hydroxy seco-steroid, D3 vitamins (CHEBI:28940) / Vitamin D3 and derivatives, Fat-soluble vitamins (C05443) / Vitamin D3 and derivatives (LMST03020000)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1C6V77QF41
- CAS number
- 67-97-0
- InChI Key
- QYSXJUFSXHHAJI-YRZJJWOYSA-N
- InChI
- InChI=1S/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26+,27-/m1/s1
- IUPAC Name
- (1S,3Z)-3-{2-[(1R,3aS,4E,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexan-1-ol
- SMILES
- CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C
References
- Synthesis Reference
Jean Jolly, Primo Rizzi, Jean Taillardat, "1.alpha.,25.alpha.-Dihydroxy-cholecalciferol and methods for the production thereof." U.S. Patent US4435325, issued May, 1977.
US4435325- General References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [Article]
- Jean G, Souberbielle JC, Chazot C: Vitamin D in Chronic Kidney Disease and Dialysis Patients. Nutrients. 2017 Mar 25;9(4). pii: nu9040328. doi: 10.3390/nu9040328. [Article]
- Heaney RP: Alendronate plus cholecalciferol for the treatment of osteoporosis. Womens Health (Lond). 2006 Jan;2(1):23-7. doi: 10.2217/17455057.2.1.23. [Article]
- DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S. [Article]
- Benaboud S, Urien S, Thervet E, Prie D, Legendre C, Souberbielle JC, Hirt D, Friedlander G, Treluyer JM, Courbebaisse M: Determination of optimal cholecalciferol treatment in renal transplant recipients using a population pharmacokinetic approach. Eur J Clin Pharmacol. 2013 Mar;69(3):499-506. doi: 10.1007/s00228-012-1378-3. Epub 2012 Aug 31. [Article]
- Jones KS, Assar S, Harnpanich D, Bouillon R, Lambrechts D, Prentice A, Schoenmakers I: 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. J Clin Endocrinol Metab. 2014 Sep;99(9):3373-81. doi: 10.1210/jc.2014-1714. Epub 2014 Jun 2. [Article]
- Borel P, Caillaud D, Cano NJ: Vitamin D bioavailability: state of the art. Crit Rev Food Sci Nutr. 2015;55(9):1193-205. doi: 10.1080/10408398.2012.688897. [Article]
- Caroline Ashley, Aileen Dunleavy (2018). The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners, 5th Edition (5th ed.). CRC Press. [ISBN:0429863632]
- Cholecalciferol (Vitamin D3) – Pharmacological Properties, Therapeutic Utility and Potential New Fields of Clinical Application by Yulian Voynikov, Georgi Momekov, Plamen Peikov [Link]
- Vitamin D Supplementation: An Update [Link]
- NIH Vitamin D Fact Sheet for Health Professionals [Link]
- Cholecalciferol Canadian Prescribing Information [File]
- Decalcitrol (coated cholecalciferol tablet) US FDA Monograph [File]
- CLH Report for Cholecalciferol [File]
- Alendronate sodium and cholecalciferol Canadian Product Monograph [File]
- External Links
- Human Metabolome Database
- HMDB0000876
- KEGG Drug
- D00188
- KEGG Compound
- C05443
- PubChem Compound
- 5280795
- PubChem Substance
- 46506365
- ChemSpider
- 4444353
- BindingDB
- 50030475
- 1244014
- ChEBI
- 28940
- ChEMBL
- CHEMBL1042
- ZINC
- ZINC000004474460
- Therapeutic Targets Database
- DAP001273
- PharmGKB
- PA164748138
- PDBe Ligand
- VD3
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Cholecalciferol
- MSDS
- Download (123 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available COVID-19, Long Haul / Long Haul COVID / Post-Acute COVID-19 / Post-acute COVID-19 (PACS), or "Long COVID" Syndrome 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Postmenopausal Osteoporosis 1 somestatus stop reason just information to hide Not Available Completed Not Available Asthma / Deficiency, Vitamin D 1 somestatus stop reason just information to hide Not Available Completed Not Available Decline, Cognitive 1 somestatus stop reason just information to hide Not Available Completed Not Available Deficiency, Vitamin D 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Chain Drug
- CVS Pharmacy
- Freeda Vitamins
- Major Pharmaceuticals
- Mason Distributors
- Merck & Co.
- MSD Frosst Iberica SA
- Pharmavite
- Physicians Total Care Inc.
- Professional Co.
- Spectrum Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral 50000 IU Ointment Topical Granule, effervescent; kit; tablet Oral Injection, solution Intramuscular; Oral Tablet, chewable Oral 1000 [iU]/1 Capsule Oral Solution Oral 50000 U.I./5ML Solution / drops Oral 10000 UI/1ML Tablet, film coated Oral 30000 U.I. Cream Topical Syrup Oral Injection, solution Parenteral Solution Intravenous 1.914 mg Bar, chewable Oral Solution Oral 25000 UI Solution Oral 50000 UI Powder, for solution Oral Capsule Oral 1000 IU Tablet, effervescent Oral 2500 mg Granule Oral Tablet, effervescent Oral Powder, for suspension Oral Tablet Oral 600.000 mg Tablet, coated Oral 1500 mg Injection, powder, for solution Intramuscular; Intravenous Injection, powder, for solution Parenteral Injection, solution Intramuscular; Intravenous Injection, powder, for solution Intravenous Kit; tablet; tablet, film coated Oral Capsule Oral Solution / drops Oral Capsule Oral 20000 IE Capsule Oral 10000 UI Capsule Oral 100000 UI Capsule Oral 25000 UI Capsule Oral 50000 UI Solution Oral 25000 UI/2.5ML Solution / drops Oral 10000 U.I./ML Solution Oral 25000 IU/2.5ml Capsule Oral 10000 I.U. Capsule Oral 25000 I.U. Solution / drops Oral 10000 UI/ML Solution Oral 50000 UI/2.5ML Capsule Oral 1000 UI Capsule Oral 20000 UI Cream Cutaneous Capsule Oral 400 unit Tablet Solution / drops Oral 400 unit / .6 mL Capsule Oral 1.25 mg/1 Solution Oral 300000 IU Solution / drops Oral 50000 IU/15ml Capsule Oral 2000 i.u. Capsule Oral 5000 i.u. Capsule Oral 50000 i.u. Solution / drops Oral 150000 i.u./10ml Solution / drops Oral 15000 i.u./ml Tablet Oral 10000 unit Solution / drops Oral 150000 iu/10ml Solution Oral 400 [iU]/1mL Capsule, liquid filled Oral 100000 IU Tablet, coated Oral 50000 [iU]/1 Capsule Oral 10000 [iU]/1 Capsule Oral 25000 [iU]/1 Capsule Oral 50000 [iU]/1 Capsule, liquid filled Oral 1000 IU Capsule, liquid filled Oral 7000 IU Capsule, liquid filled Oral 200000000 IU Tablet Oral 1000 IE Tablet Oral 400 IE Tablet Oral 500 IE Tablet, film coated Oral 2000 iu Solution / drops Oral 200000 i.u./10ml Tablet Oral 400 IU/1 Solution Intramuscular 300000 IU/ml Solution Intramuscular Capsule Oral 2000 U.I. Capsule Oral 6000 U.I. Injection, solution 100000 U.I./ml Injection, solution 300000 U.I./ml Injection, solution Intramuscular 100000 UI/ML Injection, solution Intramuscular 100000 U.I./ml Injection, solution Intramuscular 300000 UI/ML Solution Oral 100000 U.I. Solution Oral 25000 U.I./2.5ML Solution Oral 50000 U.I./2.5ML Solution / drops Oral 10000 UI Film Oral 50000 U.I. Powder, for solution Intravenous Tablet, film coated Oral 5000 IU Capsule Oral 10000 unit Capsule Oral 5000 unit Capsule Oral 50000 unit Capsule, liquid filled Oral 1 mg Capsule, liquid filled Oral 5000 IU Capsule, liquid filled; kit; tablet Oral Wafer Oral 100 unit / waf Capsule Oral 5000 IU Tablet Oral 70 mg Gel Oral Solution / drops Oral 14400 IE Solution / drops Oral 28800 IE Capsule, delayed release Oral Tablet Oral 400 IU Patch Topical 0.2 mg/100g Capsule Oral 20000 iu Tablet, chewable Oral 5000 IU Solution Oral 25000 IU Tablet, coated Oral Powder Oral Capsule Oral 2000 unit Capsule Oral 25000 unit Granule, effervescent Oral Capsule, coated Oral Suspension Oral Tablet, film coated Oral 0.125 MG Tablet Oral Tablet Oral 125 MCG Solution Oral 50000 U.I. Gel Cutaneous Solution Intramuscular; Oral Solution Intramuscular; Oral 7.5 mg Solution Oral 50000 IU/15ml Solution Intravenous Solution Oral Tablet Oral Solution Parenteral Capsule Oral 50 mg Tablet, coated Oral 1000 iu Tablet, orally disintegrating Oral Capsule, gelatin coated; kit; tablet Oral Capsule Oral 1000 U.I. Capsule Oral 10000 U.I. Capsule Oral 20000 U.I. Capsule Oral 50000 U.I. Gum, chewing Oral Solution Oral 5600 IU Solution Oral 0.00014 g Solution Oral 100000 IU Tablet, coated Oral 7000 IU Capsule, liquid filled; kit; tablet, film coated Oral Tablet, film coated Oral 1000 I.E. Tablet, film coated Oral 30000 I.E. Tablet, film coated Oral 7000 I.E. Tablet, film coated Oral 800 I.E. Solution / drops Oral 50000 i.u./15ml Liquid Oral 50000 [iU]/3mL Capsule Oral 125 MCG Capsule Oral 7 mg Powder Injection, solution; kit Intravenous Injection, solution Intravenous Suspension / drops Oral Solution / drops Oral Capsule, liquid filled; kit; tablet, coated Oral Capsule, liquid filled Oral Tablet, film coated Oral Capsule, gelatin coated Oral Pill Oral Tablet, chewable Buccal Tablet, film coated Oral Tablet, chewable Oral Wafer Oral Syrup Capsule; kit; tablet, coated Oral Capsule Oral 20000 i.u. Kit; tablet; tablet, coated Oral Powder, for solution Intramuscular; Intravenous Tablet, film coated Oral 10000 I.E. Tablet, film coated Oral 20000 I.E. Tablet, film coated Oral 5000 I.E. Solution Oral 25000 U.I. Solution Oral Liquid Oral Capsule; kit; tablet, film coated Oral Capsule; kit; tablet Oral Injection, powder, lyophilized, for solution Intramuscular; Intravenous Capsule Oral 125 mg/1 Tablet, chewable Oral 1000 IU Strip Oral Tablet Oral 1000 unit Tablet Oral 1000 IU Tablet Oral 400 unit Capsule Oral 7000 iu Tablet Oral 400 unit / tab Tablet Oral 500 IU Capsule Oral 20000 unit Capsule Oral 40000 unit Capsule, liquid filled Oral 50 ug/1 Solution Oral 25000 unit / amp Solution Oral 60000 [iU]/1 Capsule Oral 100000 unit Solution Oral 2000 IU Capsule, liquid filled Oral 2000 IU Kit Oral Solution Oral 25000 I.E. Solution Oral 50000 I.E. Capsule Oral 25000 U.I. Tablet, coated Oral Capsule Oral 100000 U.I. Injection, solution Intramuscular 300000 U.I./ml Solution Oral 100000 U.I./2.5ml Solution / drops Oral 25 ug/0.04mL Solution / drops Oral 10 ug/0.04mL Solution / drops Oral 15 ug/0.04mL Tablet, film coated Oral 10 mg Tablet, coated Oral 2000 iu Tablet, film coated Oral 1000 iu Tablet, film coated - Prices
Unit description Cost Unit Cholecalciferol crystals 104.3USD g Vitamin d3 2400 unit/ml liquid 0.8USD ml Vitamin d3 2000 unit spray 0.44USD ml Vitamin d3 3000 unit tablet 0.11USD tablet Vitamin d-3 2000 unit tablet 0.07USD tablet CVS Pharmacy vitamin d 1000 unit tablet 0.04USD tablet Delta d3 400 unit tablet 0.04USD each Vitamin d 1000 unit tablet 0.03USD tablet Pv vitamin d 2000 unit tablet 0.02USD tablet Pv vitamin d 5000 unit tablet 0.02USD tablet Vitamin d 400 unit tablet 0.02USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5994329 Yes 1999-11-30 2019-01-17 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 84.5 °C PhysProp water solubility Insoluble Not Available logP 7.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00038 mg/mL ALOGPS logP 7.98 ALOGPS logP 7.13 Chemaxon logS -6 ALOGPS pKa (Strongest Acidic) 18.38 Chemaxon pKa (Strongest Basic) -1.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 20.23 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 123.22 m3·mol-1 Chemaxon Polarizability 49.63 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.959 Caco-2 permeable + 0.8342 P-glycoprotein substrate Substrate 0.6706 P-glycoprotein inhibitor I Inhibitor 0.7603 P-glycoprotein inhibitor II Non-inhibitor 0.5346 Renal organic cation transporter Non-inhibitor 0.7818 CYP450 2C9 substrate Non-substrate 0.8384 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.7302 CYP450 1A2 substrate Non-inhibitor 0.9256 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9551 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.7881 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7093 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.921 Biodegradation Not ready biodegradable 0.9878 Rat acute toxicity 3.9310 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.773 hERG inhibition (predictor II) Non-inhibitor 0.7589
Spectra
- Mass Spec (NIST)
- Download (11.1 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0aou-3029000000-1950c74de34369a70400 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0fri-0149000000-7ae3301ba6364f84969d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-1562a1d7477455ae97ca Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-23bc946044bc596f809b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a70-4529000000-06d2a00a83ad66a96bff Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03fr-0319000000-071ea8bb1c8c6bd58dc2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01bi-4946000000-bd5ae21f84bf32da16b6 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 209.0081397 predictedDarkChem Lite v0.1.0 [M-H]- 212.5105397 predictedDarkChem Lite v0.1.0 [M-H]- 212.8281397 predictedDarkChem Lite v0.1.0 [M-H]- 208.23943 predictedDeepCCS 1.0 (2019) [M+H]+ 208.3363397 predictedDarkChem Lite v0.1.0 [M+H]+ 212.3635397 predictedDarkChem Lite v0.1.0 [M+H]+ 213.6981397 predictedDarkChem Lite v0.1.0 [M+H]+ 210.21617 predictedDeepCCS 1.0 (2019) [M+Na]+ 209.0911397 predictedDarkChem Lite v0.1.0 [M+Na]+ 212.6965397 predictedDarkChem Lite v0.1.0 [M+Na]+ 212.7794397 predictedDarkChem Lite v0.1.0 [M+Na]+ 216.12914 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638)
- Specific Function
- bile acid nuclear receptor activity
- Gene Name
- VDR
- Uniprot ID
- P11473
- Uniprot Name
- Vitamin D3 receptor
- Molecular Weight
- 48288.64 Da
References
- Reinhart GA: Vitamin D analogs: novel therapeutic agents for cardiovascular disease? Curr Opin Investig Drugs. 2004 Sep;5(9):947-51. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Fujishima T, Tsuji G, Tanaka C, Harayama H: Novel vitamin D receptor ligands having a carboxyl group as an anchor to arginine 274 in the ligand-binding domain. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):60-2. doi: 10.1016/j.jsbmb.2010.04.020. Epub 2010 May 6. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol) (PubMed:12867411, PubMed:15465040, PubMed:18511070). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives (PubMed:15465040, PubMed:18511070). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:12867411, PubMed:15465040, PubMed:18511070)
- Specific Function
- D3 vitamins binding
- Gene Name
- CYP2R1
- Uniprot ID
- Q6VVX0
- Uniprot Name
- Vitamin D 25-hydroxylase
- Molecular Weight
- 57358.82 Da
References
- Flanagan JN, Young MV, Persons KS, Wang L, Mathieu JS, Whitlatch LW, Holick MF, Chen TC: Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D. Anticancer Res. 2006 Jul-Aug;26(4A):2567-72. [Article]
- Segura-Aguilar J: Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome. Biochem Mol Med. 1996 Jun;58(1):122-9. [Article]
- Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7. [Article]
- Ohyama Y, Yamasaki T: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci. 2004 Sep 1;9:3007-18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid (PubMed:12077124, PubMed:21411718, PubMed:28190002, PubMed:9660774). Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways (PubMed:11412116, PubMed:1708392, PubMed:2019602, PubMed:7915755, PubMed:9186905, PubMed:9660774, PubMed:9790667). May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism (PubMed:12077124, PubMed:9660774). Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation (PubMed:28190002). Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium (PubMed:21411718). May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (PubMed:15465040)
- Specific Function
- 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity
- Gene Name
- CYP27A1
- Uniprot ID
- Q02318
- Uniprot Name
- Sterol 26-hydroxylase, mitochondrial
- Molecular Weight
- 60234.28 Da
References
- Lehmann B, Tiebel O, Meurer M: Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents--a preliminary study. Arch Dermatol Res. 1999 Sep;291(9):507-10. [Article]
- Sawada N, Sakaki T, Yoneda S, Kusudo T, Shinkyo R, Ohta M, Inouye K: Conversion of vitamin D3 to 1alpha,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem Biophys Res Commun. 2004 Jul 16;320(1):156-64. [Article]
- Uchida E, Kagawa N, Sakaki T, Urushino N, Sawada N, Kamakura M, Ohta M, Kato S, Inouye K: Purification and characterization of mouse CYP27B1 overproduced by an Escherichia coli system coexpressing molecular chaperonins GroEL/ES. Biochem Biophys Res Commun. 2004 Oct 15;323(2):505-11. [Article]
- Sakaki T, Kagawa N, Yamamoto K, Inouye K: Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. Print 2005 Jan 1. [Article]
- Tokar EJ, Webber MM: Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells. Clin Exp Metastasis. 2005;22(3):275-84. [Article]
- Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7. [Article]
- Ohyama Y, Yamasaki T: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci. 2004 Sep 1;9:3007-18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K, Yamada S, Terato H, Ide H, Ohyama Y: Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56. Epub 2006 Jul 13. [Article]
- Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7. [Article]
- Ohyama Y, Yamasaki T: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci. 2004 Sep 1;9:3007-18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783)
- Specific Function
- cholesterol monooxygenase (side-chain-cleaving) activity
- Gene Name
- CYP11A1
- Uniprot ID
- P05108
- Uniprot Name
- Cholesterol side-chain cleavage enzyme, mitochondrial
- Molecular Weight
- 60101.87 Da
References
- Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, Slominski A: Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):213-9. doi: 10.1016/j.jsbmb.2008.10.005. Epub 2008 Oct 21. [Article]
- Tuckey RC, Nguyen MN, Slominski A: Kinetics of vitamin D3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin. Int J Biochem Cell Biol. 2008;40(11):2619-26. doi: 10.1016/j.biocel.2008.05.006. Epub 2008 May 20. [Article]
- Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW: A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14754-9. Epub 2003 Dec 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Yamazaki H, Shimada T: Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by human cytochrome P450 enzymes. Xenobiotica. 1999 Mar;29(3):231-41. doi: 10.1080/004982599238632 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- This enzyme action is supported by the results of 1 in vitro study. The clinical correlation is unknown.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Yamazaki H, Shimada T: Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by human cytochrome P450 enzymes. Xenobiotica. 1999 Mar;29(3):231-41. doi: 10.1080/004982599238632 . [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation
- Specific Function
- actin binding
- Gene Name
- GC
- Uniprot ID
- P02774
- Uniprot Name
- Vitamin D-binding protein
- Molecular Weight
- 52916.915 Da
References
- Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE: An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999 Feb 19;96(4):507-15. [Article]
- Verboven C, Rabijns A, De Maeyer M, Van Baelen H, Bouillon R, De Ranter C: A structural basis for the unique binding features of the human vitamin D-binding protein. Nat Struct Biol. 2002 Feb;9(2):131-6. [Article]
- Houghton LA, Vieth R: The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7. [Article]
- Yamamoto N, Naraparaju VR: Vitamin D3-binding protein as a precursor for macrophage activating factor in the inflammation-primed macrophage activation cascade in rats. Cell Immunol. 1996 Jun 15;170(2):161-7. [Article]
- Yamamoto N, Naraparaju VR: Role of vitamin D3-binding protein in activation of mouse macrophages. J Immunol. 1996 Aug 15;157(4):1744-9. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 03:51