Target Information
Target General Information | Top | |||||
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Target ID |
T34234
(Former ID: TTDS00251)
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Target Name |
Vitamin D3 receptor (VDR)
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Synonyms |
Vitamin D(3) receptor; Nuclear vitamin D receptor; Nuclear receptor subfamily 1 group I member 1; NR1I1; 1,25-dihydroxyvitamin D3 receptor
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Gene Name |
VDR
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 7 Target-related Diseases | + | ||||
1 | Chronic kidney disease [ICD-11: GB61] | |||||
2 | Hair/hair growth developmental defect [ICD-11: LC30] | |||||
3 | Hyper-parathyroidism [ICD-11: 5A51] | |||||
4 | Hypo-parathyroidism [ICD-11: 5A50] | |||||
5 | Mineral deficiency [ICD-11: 5B5K] | |||||
6 | Psoriasis [ICD-11: EA90] | |||||
7 | Vitamin deficiency [ICD-11: 5B55-5B5F] | |||||
Function |
Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.
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BioChemical Class |
Nuclear hormone receptor
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UniProt ID | ||||||
Sequence |
MEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTC
PFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEEVQRKREMILKRKEEEALKDSL RPKLSEEQQRIIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSG DSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLELSQLSMLPHLADLVSYSIQK VIGFAKMIPGFRDLTSEDQIVLLKSSAIEVIMLRSNESFTMDDMSWTCGNQDYKYRVSDV TKAGHSLELIEPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLS NTLQTYIRCRHPPPGSHLLYAKMIQKLADLRSLNEEHSKQYRCLSFQPECSMKLTPLVLE VFGNEIS Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T85JI5 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 9 Approved Drugs | + | ||||
1 | Calcidiol | Drug Info | Approved | Vitamin D deficiency | [2], [3] | |
2 | Calcipotriol | Drug Info | Approved | Psoriasis vulgaris | [4], [5] | |
3 | Calcitriol | Drug Info | Approved | Congenital alopecia | [6], [7] | |
4 | Cholecalciferol | Drug Info | Approved | Vitamin D deficiency | [8], [9] | |
5 | Dihydrotachysterol | Drug Info | Approved | Hypocalcemia | [10] | |
6 | Doxercalciferol | Drug Info | Approved | Chronic kidney disease | [11], [12] | |
7 | Ergocalciferol | Drug Info | Approved | Hypoparathyroidism | [13] | |
8 | Falecalcitrol | Drug Info | Approved | Hyperparathyroidism | [10] | |
9 | Paricalcitol | Drug Info | Approved | Hyperparathyroidism | [5], [14] | |
Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
1 | S-06911 | Drug Info | Phase 3 | Osteoporosis | [15] | |
2 | Seocalcitol | Drug Info | Phase 3 | Rickets | [16], [17] | |
3 | Inecalcitol oral | Drug Info | Phase 2 | Prostate cancer | [18], [19] | |
4 | CTAP-201 | Drug Info | Phase 1 | Hyperparathyroidism | [20] | |
5 | RO-23-7553 | Drug Info | Phase 1 | Prostate disease | [21] | |
Discontinued Drug(s) | [+] 8 Discontinued Drugs | + | ||||
1 | Atocalcitol | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [22] | |
2 | Lexacalcitol | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [23], [24] | |
3 | RO-26-9228 | Drug Info | Discontinued in Phase 2 | Urinary incontinence | [25], [26] | |
4 | Tisocalcitate | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [27] | |
5 | BXL-746 | Drug Info | Discontinued in Phase 1 | Inflammation | [28] | |
6 | CB-1267 | Drug Info | Terminated | Prostate cancer | [29] | |
7 | CEP-4186 | Drug Info | Terminated | Acute myeloid leukaemia | [30] | |
8 | Ecalcidene | Drug Info | Terminated | Acne vulgaris | [31] | |
Mode of Action | [+] 6 Modes of Action | + | ||||
Antagonist | [+] 7 Antagonist drugs | + | ||||
1 | Calcidiol | Drug Info | [1], [32] | |||
2 | Calcipotriol | Drug Info | [33] | |||
3 | Dihydrotachysterol | Drug Info | [37], [32] | |||
4 | Doxercalciferol | Drug Info | [12] | |||
5 | Ergocalciferol | Drug Info | [1], [32] | |||
6 | TEI-9647 | Drug Info | [60] | |||
7 | ZK159222 | Drug Info | [61] | |||
Agonist | [+] 26 Agonist drugs | + | ||||
1 | Calcitriol | Drug Info | [34] | |||
2 | Falecalcitrol | Drug Info | [38] | |||
3 | Paricalcitol | Drug Info | [39] | |||
4 | Inecalcitol oral | Drug Info | [19], [42] | |||
5 | CTAP-201 | Drug Info | [43] | |||
6 | RO-23-7553 | Drug Info | [44], [10] | |||
7 | PMID27454349-Compound-100 | Drug Info | [45] | |||
8 | PMID27454349-Compound-101 | Drug Info | [45] | |||
9 | PMID27454349-Compound-102 | Drug Info | [45] | |||
10 | PMID27454349-Compound-91 | Drug Info | [45] | |||
11 | PMID27454349-Compound-92 | Drug Info | [45] | |||
12 | PMID27454349-Compound-93 | Drug Info | [45] | |||
13 | PMID27454349-Compound-94 | Drug Info | [45] | |||
14 | PMID27454349-Compound-95 | Drug Info | [45] | |||
15 | PMID27454349-Compound-96 | Drug Info | [45] | |||
16 | PMID27454349-Compound-97 | Drug Info | [45] | |||
17 | PMID27454349-Compound-98 | Drug Info | [45] | |||
18 | PMID27454349-Compound-99 | Drug Info | [45] | |||
19 | Atocalcitol | Drug Info | [46] | |||
20 | Lexacalcitol | Drug Info | [47] | |||
21 | RO-26-9228 | Drug Info | [40] | |||
22 | 2MD | Drug Info | [53] | |||
23 | 3-keto-lithocholic acid | Drug Info | [54] | |||
24 | calcitriol-26,23-lactone | Drug Info | [55] | |||
25 | gemini | Drug Info | [56] | |||
26 | LG190178 | Drug Info | [58] | |||
Binder | [+] 1 Binder drugs | + | ||||
1 | Cholecalciferol | Drug Info | [32], [35], [36] | |||
Inhibitor | [+] 5 Inhibitor drugs | + | ||||
1 | S-06911 | Drug Info | [40] | |||
2 | Seocalcitol | Drug Info | [41] | |||
3 | Tisocalcitate | Drug Info | [48] | |||
4 | KSP-BCS-1-alpha-CHF2-1624F2-2 | Drug Info | [57] | |||
5 | KSP-BCS-1-alpha-CHF2-20-epi-22-oxabishomo-26-OH | Drug Info | [57] | |||
Stimulator | [+] 1 Stimulator drugs | + | ||||
1 | BXL-746 | Drug Info | [49] | |||
Modulator | [+] 4 Modulator drugs | + | ||||
1 | CB-1267 | Drug Info | [50] | |||
2 | CEP-4186 | Drug Info | [51] | |||
3 | Ecalcidene | Drug Info | [52] | |||
4 | MC-1301 | Drug Info | [59] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Endocrine and other factor-regulated calcium reabsorption | |||||
2 | Mineral absorption | |||||
3 | Tuberculosis | |||||
NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | IL4 Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Vitamin D metabolism and pathway | |||||
PID Pathway | [+] 6 PID Pathways | + | ||||
1 | Regulation of nuclear SMAD2/3 signaling | |||||
2 | Direct p53 effectors | |||||
3 | RXR and RAR heterodimerization with other nuclear receptor | |||||
4 | Retinoic acid receptors-mediated signaling | |||||
5 | Validated transcriptional targets of deltaNp63 isoforms | |||||
6 | Validated transcriptional targets of TAp63 isoforms | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Nuclear Receptor transcription pathway | |||||
WikiPathways | [+] 7 WikiPathways | + | ||||
1 | Ovarian Infertility Genes | |||||
2 | Nuclear Receptors in Lipid Metabolism and Toxicity | |||||
3 | Nuclear Receptors Meta-Pathway | |||||
4 | Vitamin D Receptor Pathway | |||||
5 | Drug Induction of Bile Acid Pathway | |||||
6 | Nuclear Receptors | |||||
7 | Vitamin D Metabolism |
Target-Related Models and Studies | Top | |||||
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Target Validation | ||||||
Target QSAR Model |
References | Top | |||||
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REF 1 | Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6921). | |||||
REF 3 | Drug Information of Carbetocin from nextbio research in illumina. 2015. | |||||
REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2778). | |||||
REF 5 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2779). | |||||
REF 7 | ClinicalTrials.gov (NCT02186665) Plaque Psoriasis Study in Pediatric Subjects. U.S. National Institutes of Health. | |||||
REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2747). | |||||
REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021762. | |||||
REF 10 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 11 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2790). | |||||
REF 12 | Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. | |||||
REF 13 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040833. | |||||
REF 14 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2791). | |||||
REF 15 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 700201063) | |||||
REF 16 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2777). | |||||
REF 17 | Seocalcitol (EB 1089): a vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Curr Pharm Des. 2000 May;6(7):803-28. | |||||
REF 18 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7747). | |||||
REF 19 | Inecalcitol, an analog of 1,25D3, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system. Cell Cycle. 2013 Mar 1;12(5):743-52. | |||||
REF 20 | ClinicalTrials.gov (NCT00792857) Comparison of I.V. CTAP201 and Doxercalciferol (Hectorol) in Subjects With Chronic Kidney Disease (CKD) and Secondary Hyperparathyroidism (SHPT). U.S. National Institutes of Health. | |||||
REF 21 | ClinicalTrials.gov (NCT00004926) ILX23-7553 in Treating Patients With Solid Tumors That Have Not Responded to Previous Therapy. U.S. National Institutes of Health. | |||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014844) | |||||
REF 23 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2775). | |||||
REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002985) | |||||
REF 25 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2785). | |||||
REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015074) | |||||
REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018814) | |||||
REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025073) | |||||
REF 29 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007891) | |||||
REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012493) | |||||
REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019289) | |||||
REF 32 | Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S. | |||||
REF 33 | Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr;9(4):345-59. | |||||
REF 34 | Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94. | |||||
REF 35 | [Vitamin D2 or vitamin D3]. Rev Med Interne. 2008 Oct;29(10):815-20. | |||||
REF 36 | Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-gamma genes and its association with susceptibility to tuberculosis. Braz J Med Biol Res. 2009 Apr;42(4):312-22. | |||||
REF 37 | In vivo metabolism of the vitamin D analog, dihydrotachysterol. Evidence for formation of 1 alpha,25- and 1 beta,25-dihydroxy-dihydrotachysterol metabolites and studies of their biological activity. J Biol Chem. 1993 Jan 5;268(1):282-92. | |||||
REF 38 | Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3. Bioorg Med Chem. 2000 Aug;8(8):2157-66. | |||||
REF 39 | New acquisitions in therapy of secondary hyperparathyroidism in chronic kidney disease and peritoneal dialysis patients: role of vitamin D receptor... Contrib Nephrol. 2009;163:219-226. | |||||
REF 40 | Evidence for tissue- and cell-type selective activation of the vitamin D receptor by Ro-26-9228, a noncalcemic analog of vitamin D3. J Cell Biochem. 2003 Feb 1;88(2):267-73. | |||||
REF 41 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 42 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 43 | Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. Br J Pharmacol. 2009 April; 156(8): 1267-1278. | |||||
REF 44 | Three synthetic vitamin D analogues induce prostate-specific acid phosphatase and prostate-specific antigen while inhibiting the growth of human prostate cancer cells in a vitamin D receptor-dependent fashion. Clin Cancer Res. 1997 Aug;3(8):1331-8. | |||||
REF 45 | Vitamin D receptor 2016: novel ligands and structural insights.Expert Opin Ther Pat. 2016 Nov;26(11):1291-1306. | |||||
REF 46 | Elocalcitol, a vitamin D3 analog for the potential treatment of benign prostatic hyperplasia, overactive bladder and male infertility. IDrugs. 2009 Jun;12(6):381-93. | |||||
REF 47 | The vitamin D analog, KH1060, is rapidly degraded both in vivo and in vitro via several pathways: principal metabolites generated retain significant biological activity. Endocrinology. 1997 Dec;138(12):5485-96. | |||||
REF 48 | The Rationale Behind Topical Vitamin D Analogs in the Treatment of Psoriasis: Where Does Topical Calcitriol Fit In . J Clin Aesthet Dermatol. 2010 August; 3(8): 46-53. | |||||
REF 49 | Inter-species differences in sensitivity to the calcemic activity of the novel 1,25-dihydroxyvitamin D3 analog BXL746. Regul Toxicol Pharmacol. 2008 Dec;52(3):332-41. | |||||
REF 50 | Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells. Prostate. 1999 Aug 1;40(3):141-9. | |||||
REF 51 | Novel vitamin D3 analog (CB1093) when combined with paclitaxel and cisplatin inhibit growth of MCF-7 human breast cancer cells in vivo. Int J Oncol. 1998 Sep;13(3):421-8. | |||||
REF 52 | Degradation chemistry of a Vitamin D analogue (ecalcidene) investigated by HPLC-MS, HPLC-NMR and chemical derivatization. J Pharm Biomed Anal. 2006 Mar 3;40(4):850-63. | |||||
REF 53 | New 1alpha,25-dihydroxy-19-norvitamin D3 compounds of high biological activity: synthesis and biological evaluation of 2-hydroxymethyl, 2-methyl, and 2-methylene analogues. J Med Chem. 1998 Nov 5;41(23):4662-74. | |||||
REF 54 | Vitamin D receptor as an intestinal bile acid sensor. Science. 2002 May 17;296(5571):1313-6. | |||||
REF 55 | Biological activity of 24,24-difluoro-1 alpha, 25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone in inducing differentiation of human myeloid leukemia cells. Arch Biochem Biophys. 1983 Jan;220(1):90-4. | |||||
REF 56 | Novel Gemini analogs of 1alpha,25-dihydroxyvitamin D(3) with enhanced transcriptional activity. Biochem Pharmacol. 2004 Apr 1;67(7):1327-36. | |||||
REF 57 | Low-calcemic, highly antiproliferative, 1-difluoromethyl hybrid analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: design, synthesis, an... J Med Chem. 2006 Dec 14;49(25):7513-7. | |||||
REF 58 | Novel nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3. Chem Biol. 1999 May;6(5):265-75. | |||||
REF 59 | Effects of 1,25-dihydroxyvitamin D3 and its 20-epi analogues (MC 1288, MC 1301, KH 1060), on clonal keratinocyte growth: evidence for differentiati... Br J Pharmacol. 1997 Mar;120(6):1119-27. | |||||
REF 60 | Further synthetic and biological studies on vitamin D hormone antagonists based on C24-alkylation and C2alpha-functionalization of 25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones. J Med Chem. 2006 Nov 30;49(24):7063-75. | |||||
REF 61 | Carboxylic ester antagonists of 1alpha,25-dihydroxyvitamin D(3) show cell-specific actions. Chem Biol. 2000 Nov;7(11):885-94. |
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