Target Information
| Target General Information | Top | |||||
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| Target ID |
T72168
(Former ID: TTDS00206)
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| Target Name |
Mineralocorticoid receptor (MR)
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| Synonyms |
Nuclear receptor subfamily 3 group C member 2; Mineralocorticoid receptor; MLR; MCR; Inner ear mineralocorticoid receptor; Delta
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| Gene Name |
NR3C2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Adrenocortical insufficiency [ICD-11: 5A74] | |||||
| 2 | Contraceptive management [ICD-11: QA21] | |||||
| 3 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| 4 | Hypertension [ICD-11: BA00-BA04] | |||||
| 5 | Hypo-osmolality/hyponatraemia [ICD-11: 5C72] | |||||
| Function |
Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol.
Click to Show/Hide
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| BioChemical Class |
Nuclear hormone receptor
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| UniProt ID | ||||||
| Sequence |
METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNST
QGSSKEKQELLPCLQQDNNRPGILTSDIKTELESKELSATVAESMGLYMDSVRDADYSYE QQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPN VENRGSRSHSPAHASNVGSPLSSPLSSMKSSISSPPSHCSVKSPVSSPNNVTLRSSVSSP ANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSD SSFSVPIKQESTKHSCSGTSFKGNPTVNPFPFMDGSYFSFMDDKDYYSLSGILGPPVPGF DGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPS KICLVCGDEASGCHYGVVTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRL QKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVN TALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQV VKWAKVLPGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKM HQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYI KELRKMVTKCPNNSGQSWQRFYQLTKLLDSMHDLVSDLLEFCFYTFRESHALKVEFPAML VEIISDQLPKVESGNAKPLYFHRK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T64F54 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 7 Approved Drugs | + | ||||
| 1 | Aldosterone | Drug Info | Approved | Hypertension | [2], [3] | |
| 2 | Desoxycorticosterone Acetate | Drug Info | Approved | Discovery agent | [4] | |
| 3 | Desoxycorticosterone Pivalate | Drug Info | Approved | Addison disease | [5] | |
| 4 | Drospirenone | Drug Info | Approved | Contraception | [6], [7] | |
| 5 | Eplerenone | Drug Info | Approved | Heart failure | [7], [8] | |
| 6 | Fludrocortisone | Drug Info | Approved | Cerebral salt-wasting syndrome | [9], [10] | |
| 7 | Spironolactone | Drug Info | Approved | Congestive heart failure | [11], [12] | |
| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | Finerenone | Drug Info | Phase 3 | Diabetic nephropathy | [13] | |
| 2 | BR-4628 | Drug Info | Phase 2 | Heart failure | [14] | |
| 3 | LY-2623091 | Drug Info | Phase 2 | Chronic kidney disease | [15] | |
| 4 | MT-3995 | Drug Info | Phase 2 | Diabetic nephropathy | [16] | |
| 5 | Nerenone | Drug Info | Phase 2 | Diabetic nephropathy | [17] | |
| 6 | ZK-91587 | Drug Info | Phase 2 | Cardiovascular disease | [18] | |
| 7 | KBP-5074 | Drug Info | Phase 1/2 | Hypertension | [19] | |
| 8 | XL550 | Drug Info | Phase 1 | Type-2 diabetes | [20] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | PF-03882845 | Drug Info | Terminated | Diabetic nephropathy | [21] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Agonist | [+] 3 Agonist drugs | + | ||||
| 1 | Aldosterone | Drug Info | [22] | |||
| 2 | Fludrocortisone | Drug Info | [1], [26] | |||
| 3 | deoxycorticosterone | Drug Info | [34] | |||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Desoxycorticosterone Acetate | Drug Info | [23] | |||
| 2 | Eplerenone | Drug Info | [23] | |||
| 3 | Spironolactone | Drug Info | [23] | |||
| 4 | PF-03882845 | Drug Info | [30] | |||
| Binder | [+] 2 Binder drugs | + | ||||
| 1 | Desoxycorticosterone Pivalate | Drug Info | [24] | |||
| 2 | Drospirenone | Drug Info | [25] | |||
| Antagonist | [+] 15 Antagonist drugs | + | ||||
| 1 | Finerenone | Drug Info | [13] | |||
| 2 | BR-4628 | Drug Info | [27] | |||
| 3 | LY-2623091 | Drug Info | [28] | |||
| 4 | MT-3995 | Drug Info | [28] | |||
| 5 | Nerenone | Drug Info | [27] | |||
| 6 | ZK-91587 | Drug Info | [4], [18] | |||
| 7 | KBP-5074 | Drug Info | [19] | |||
| 8 | XL550 | Drug Info | [20] | |||
| 9 | PMID27551786-Compound-106 | Drug Info | [29] | |||
| 10 | PMID27551786-Compound-138 | Drug Info | [29] | |||
| 11 | PMID27551786-Compound-I | Drug Info | [29] | |||
| 12 | PMID27551786-Compound-II | Drug Info | [29] | |||
| 13 | PMID27551786-Compound-III | Drug Info | [29] | |||
| 14 | PMID27551786-Compound-IV | Drug Info | [29] | |||
| 15 | RU28318 | Drug Info | [27] | |||
| Inhibitor | [+] 8 Inhibitor drugs | + | ||||
| 1 | (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE | Drug Info | [31] | |||
| 2 | AL-43 | Drug Info | [32] | |||
| 3 | B-Octylglucoside | Drug Info | [33] | |||
| 4 | CB-1922 | Drug Info | [27] | |||
| 5 | Epierenone | Drug Info | [35] | |||
| 6 | LG-120838 | Drug Info | [36] | |||
| 7 | LGD-5552 | Drug Info | [37] | |||
| 8 | WAY-255348 | Drug Info | [38] | |||
| 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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Aldosterone-regulated sodium reabsorption | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Kidney Function | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | ACE Inhibitor Pathway | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans. J Gerontol A Biol Sci Med Sci. 2003 Oct;58(10):B900-5. | |||||
| 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: 2872). | |||||
| REF 3 | Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update. J Hum Hypertens. 2007 Sep;21(9):699-708. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Drug information of Desoxycorticosterone Pivalate, 2008. eduDrugs. | |||||
| 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: 2874). | |||||
| REF 7 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| 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: 2876). | |||||
| REF 9 | 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: 2873). | |||||
| REF 10 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010060. | |||||
| 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: 2875). | |||||
| REF 12 | Emerging drugs for complications of end-stage liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):159-74. | |||||
| REF 13 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027127) | |||||
| REF 15 | ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health. | |||||
| REF 16 | ClinicalTrials.gov (NCT01756703) A Study to Evaluate Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of MT-3995 in Type II Diabetic Nephropathy Subjects With Albuminuria. U.S. National Institutes of Health. | |||||
| REF 17 | Clinical pipeline report, company report or official report of Bayer HealthCare Pharmaceuticals. | |||||
| REF 18 | ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus. Life Sci. 1988;43(19):1537-43. | |||||
| REF 19 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 20 | Clinical pipeline report, company report or official report of Exelixis (2011). | |||||
| REF 21 | Clinical pipeline report, company report or official report of Pfizer (2011). | |||||
| REF 22 | Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005 Nov 24;243(1-2):35-42. | |||||
| REF 23 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 24 | Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51. | |||||
| REF 25 | Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78. | |||||
| REF 26 | Addison's disease. BMJ. 2009 Jul 2;339:b2385. | |||||
| REF 27 | 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. (Target id: 626). | |||||
| REF 28 | Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):417-24. | |||||
| REF 29 | Mineralocorticoid receptor antagonists: a patent evaluation of US20150284376A1.Expert Opin Ther Pat. 2016 Sep 14:1-4. | |||||
| REF 30 | Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g] indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy.J Med Chem.2010 Aug 26;53(16):5979-6002. | |||||
| REF 31 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 32 | Nonsteroidal selective glucocorticoid modulators: the effect of C-10 substitution on receptor selectivity and functional potency of 5-allyl-2,5-dih... J Med Chem. 2003 Mar 13;46(6):1016-30. | |||||
| REF 33 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 34 | Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol. 1993 Oct 15;247(2):145-54. | |||||
| REF 35 | (S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of the mine... J Med Chem. 2007 Dec 27;50(26):6443-5. | |||||
| REF 36 | 5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists. J Med Chem. 1998 Oct 22;41(22):4354-9. | |||||
| REF 37 | Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9. | |||||
| REF 38 | Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-... J Med Chem. 2008 Mar 27;51(6):1861-73. | |||||
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