Repositioning Candidate Details
| Candidate ID: | R0024 |
| Source ID: | DB00146 |
| Source Type: | approved; nutraceutical |
| Compound Type: | small molecule |
| Compound Name: | Calcifediol |
| Synonyms: | |
| Molecular Formula: | C27H44O2 |
| SMILES: | C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C |
| Structure: |
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| DrugBank Description: | The major circulating metabolite of vitamin D3 (cholecalciferol). It is produced in the liver and is the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. |
| CAS Number: | 19356-17-3 |
| Molecular Weight: | 400.6371 |
| DrugBank Indication: | Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis. |
| DrugBank Pharmacology: | Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. |
| DrugBank MoA: | Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. |
| Targets: | Vitamin D3 receptor |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S07 | antihypertensive | Anti-fibrosis; Anti-hypertensive; Anti-hypertensive; antihypertensive medications; multidrug combination antihypertensive treatment; empirical addition (or increase in the dose) of an antihypertensive agent of a different class""; Anti-hypertensive; Lifestyle measures; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Immunotherapy; Anti-hypertensive; Immunosuppressive treatment; Anti-hypertensive; Anti-hypertensive; Anti-platelet aggregation; other antihypertensive drugs; antihypertensive therapy; Anti-hypertensive; Anti-inflammatory; Anti-hypertensive (standard antihypertensive treatment; intensive antihypertensive treatment); Blood pressure management; Anti-hypertensive; Enhance lipid metabolism; Anti-hypertensive; Enhance lipid metabolism; Anti-platelet aggregation; Improve insulin resistance; Anti-hypertensive; Anti-hypertensive; Anti-oxidative stress; antihypertensives; Lifestyle measures; Anti-hypertensive; Anti-fibrosis; Anti-inflammatory; Anti-hypertensive | ACE; Smad4; PKD1; angiotensin receptor; SGLT2; angiotensin II receptor; mineralocorticoid receptor; ACE | riociguat; sGC stimulators; sGC activators; antihypertensive medications; carvedilol; lercanidipine; enalapril; folic acid; retinoic acid; angiotensin II; antihypertensive drug; Tripterygium Wilfordii Hook F; valsartan; Renin-angiotensin system inhibitors; diuretics; calcium channel blocker; corticosteroid; anti-hypertensive treatment; NSAIDs; naproxen; celecoxib; proton pump inhibitor; non-selective NSAID; selective cyclo-oxygenase-2 inhibitor; renin-angiotensin system blockers; antihypertensive agent; cilnidipine; valsartan; RAAS-is; steroids; immunosuppressors; amiloride; hydrochlorothiazide; berberine; Aliskiren; calcium channel blocker; angiotensin II receptor blocker; ARB; Chlorthalidone; Hydrochlorothiazide; Hsub2/subS; NO; Hsub2/subSxa0; xa0; NO; prednisolone; mizoribine; angiotensin-converting enzyme inhibitors; ACEI; eculizumab; antihypertensive agents; antithrombotics; antianemics; proton pump inhibitors; allopurinol; rilmenidine; long-term benzodiazepines; anticholinergic drugs; hydroxyzine; Qian Yang Yu Yin Granule; RAAS blockers; other antihypertensive drugs; antihypertensives; antihypertensive classes; antihypertensive therapy; melatonin; RAASi; Aliskiren; ARBs; ACEIs; tegafur/gimeracil/oteracil; furosemide; prednisolone; angiotensin receptor blockers; valsartan; antihypertensive drugs; fosinopril; valsartan; Canagliflozin; sodium glucose co-transporter 2 inhibitors; Aspirin; Antihypertensive; Lipid-Lowering Treatment; Sodium-glucose cotransporter 2 inhibitors; angiotensin II receptor blocker; Spironolactone; KBP-5074; captopril; enalaprilate; lisinopril; losartan; valsartan; furosemide; pravastatin; simvastatin; Renin Angiotensin System inhibitors; ACE inhibitors; diuretics; β-blockers; Thiazide diuretics; dihydropyridine calcium-channel blockers; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; calcium-channel blockers; thiazide-like diuretics; lisinopril; Edarbyclor; azilsartan medoxomil; chlorthalidone; hydrochlorothiazide; aliskiren; ARB; enalapril; non-steroidalanti-inflammatory drugs; antihypertensive treatment; Chlorthalidone; loop diuretics; angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; statin; captopril; tiopronin; active form of dalcetrapib; active metabolite of prasugrel, R-138727; Liuwei Dihuang pills; metformin hydrochloride sustained-release tablets; irbesartan tablets; renin-angiotensin-aldosterone system inhibitor; type 1 angiotensin II receptor blockade; olmesartan; steroid; immunosuppressive agents; enalapril; corticosteroid treatment; Angiotensin-converting-enzyme inhibitors; antihypertensives; GLP-1 receptor analogue; SGLT2-inhibitor; sacubitril/valsartan; valsartan; Sulodexide; liraglutide; enalapril; ACE-I/ARBs; angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers; labetalol; ACEi; ARB; ARBs | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T06 | Sulfonylurea receptor 1 | ABCC8 | Target is a single protein chain | Q09428 | ABCC8_HUMAN | Details | |
| T41 | Solute carrier family 13 member 5 | SLC13A5 | Target is a single protein chain | Q86YT5 | SLC13A5_HUMAN | Details | |
| T13 | Renin | REN | INHIBITOR | Target is a single protein chain | P00797 | REN_HUMAN | Details |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |