Target Information

Target General Infomation
Target ID
T72168
Former ID
TTDS00206
Target Name
Mineralocorticoid receptor
Gene Name
NR3C2
Synonyms
Delta; Inner ear mineralocorticoid receptor; MR; NR3C2
Target Type
Successful
Disease Addison's disease [ICD9: 255.4; ICD10: E27.1-E27.2]
Cardiovascular disorder [ICD10: I00-I99]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Congestive heart failure [ICD9: 428; ICD10: I50]
Chronic kidney disease [ICD9: 403, 585.1-585.5, 585.9; ICD10: N18]
Cerebral salt-wasting syndrome [ICD10: E87.1]
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21]
Heart failure [ICD9: 428; ICD10: I50]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Oral contraceptive [ICD10: Z30]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Unspecified [ICD code not available]
Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. 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.
BioChemical Class
Zinc-finger
Target Validation
T72168
UniProt ID
P08235
Sequence
METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNST
QGSSKEKQELLPCLQQDNNRPGILTSDIKTELESKELSATVAESMGLYMDSVRDADYSYE
QQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAI
VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPN
AENRGSRSHSPAHASNVGSPLSSPLSSMKSSISSPPSHCSVKSPVSSPNNVTLRSSVSSP
ANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP
SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSD
SSFSVPIKQESTKHSCSGTSFKGNPTVNPFPFMDGSYFSFMDDKDYYSLSGILGPPVPGF
DGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR
DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPS
KICLVCGDEASGCHYGVVTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRL
QKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVN
TALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQV
VKWAKVLPGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKM
HQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYI
KELRKMVTKCPNNSGQSWQRFYQLTKLLDSMHDLVSDLLEFCFYTFRESHALKVEFPAML
VEIISDQLPKVESGNAKPLYFHRK
Drugs and Mode of Action
Drug(s) Desoxycorticosterone Acetate Drug Info Approved Unspecified [1]
Desoxycorticosterone Pivalate Drug Info Approved Addison's disease [2]
Drospirenone Drug Info Approved Oral contraceptive [3], [4]
Eplerenone Drug Info Approved Heart failure [3], [5]
Fludrocortisone Drug Info Approved Cerebral salt-wasting syndrome [6], [7]
Spironolactone Drug Info Approved Congestive heart failure [8], [9]
BR-4628 Drug Info Phase 2 Heart failure [10]
LY-2623091 Drug Info Phase 2 Chronic kidney disease [11]
MT-3995 Drug Info Phase 2 Diabetic nephropathy [12]
Nerenone Drug Info Phase 2 Diabetic nephropathy [13]
ZK-91587 Drug Info Phase 2 Cardiovascular disorder [14]
XL550 Drug Info Phase 1 Type 2 diabetes [15]
PF-03882845 Drug Info Terminated Diabetic nephropathy [16]
Inhibitor (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE Drug Info [17]
AL-43 Drug Info [18]
B-Octylglucoside Drug Info [19]
CB-1922 Drug Info [20]
EPIERENONE Drug Info [21]
LG-120838 Drug Info [22]
LGD-5552 Drug Info [23]
WAY-255348 Drug Info [24]
Antagonist BR-4628 Drug Info [20]
LY-2623091 Drug Info [25]
MT-3995 Drug Info [25]
Nerenone Drug Info [20]
RU28318 Drug Info [20]
XL550 Drug Info [15]
ZK-91587 Drug Info [14], [1]
Agonist deoxycorticosterone Drug Info [26]
Fludrocortisone Drug Info [27], [28]
[3H]aldosterone Drug Info [29]
Modulator Desoxycorticosterone Acetate Drug Info [30]
Eplerenone Drug Info [30]
PF-03882845 Drug Info
Spironolactone Drug Info [30]
Binder Desoxycorticosterone Pivalate Drug Info [31]
Drospirenone Drug Info [32]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Aldosterone-regulated sodium reabsorption
PathWhiz Pathway Kidney Function
WikiPathways ACE Inhibitor Pathway
References
REF 1Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 2Drug information of Desoxycorticosterone Pivalate, 2008. eduDrugs.
REF 3Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 4(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 5(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 6FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010060.
REF 7(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 8Emerging drugs for complications of end-stage liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):159-74.
REF 9(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 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027127)
REF 11ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health.
REF 12ClinicalTrials.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 13Clinical pipeline report, company report or official report of Bayer HealthCare Pharmaceuticals.
REF 14ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus. Life Sci. 1988;43(19):1537-43.
REF 15Clinical pipeline report, company report or official report of Exelixis (2011).
REF 16Clinical pipeline report, company report or official report of Pfizer (2011).
REF 17The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 18J Med Chem. 2003 Mar 13;46(6):1016-30.Nonsteroidal selective glucocorticoid modulators: the effect of C-10 substitution on receptor selectivity and functional potency of 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines.
REF 19How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 20(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 21J Med Chem. 2007 Dec 27;50(26):6443-5. Epub 2007 Nov 27.(S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of themineralocorticoid receptor.
REF 22J Med Chem. 1998 Oct 22;41(22):4354-9.5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists.
REF 23Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9. Epub 2007 Nov 21.Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile.
REF 24J Med Chem. 2008 Mar 27;51(6):1861-73. Epub 2008 Mar 5.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-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (WAY-255348).
REF 25Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):417-24.
REF 26Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol. 1993 Oct 15;247(2):145-54.
REF 27Mineralocorticoid 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 28Addison's disease. BMJ. 2009 Jul 2;339:b2385. doi: 10.1136/bmj.b2385.
REF 29Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005 Nov 24;243(1-2):35-42. Epub 2005 Sep 26.
REF 30Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 31Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51.
REF 32Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and safety.

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