Target Information

Target General Infomation
Target ID
T22939
Former ID
TTDS00245
Target Name
Progesterone receptor
Gene Name
PGR
Synonyms
PR; PGR
Target Type
Successful
Disease Advanced breast carcinoma; Advanced endometrium carcinoma [ICD9: 174, 175, 182.0; ICD10: C50, C54.1]
Contraception [ICD10: Z30]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Dysmenorrhea [ICD9: 625.3; ICD10: N94.4-N94.6]
Endometrial cancer [ICD9: 182; ICD10: C54.1]
Endometriosis [ICD9: 617; ICD10: N80]
Estrogen deficiency [ICD10: E28.39]
Female contraception [ICD10: Z30]
Gynecological disorder [ICD10: N70-N98]
Hormonal contraceptives [ICD10: Z30]
Menstrual disorders [ICD9: 626; ICD10: N91-N95]
Osteoporosis [ICD9: 733.0, V07.4; ICD10: M80-M81, Z79.890]
Premature labour [ICD9: 644, 765; ICD10: O60.1, P07.3]
Uterine leiomyoma [ICD9: 218.9; ICD10: D25]
Uterine fibroids [ICD10: D25]
Unspecified [ICD code not available]
Function
Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
BioChemical Class
Zinc-finger
Target Validation
T22939
UniProt ID
P06401
Sequence
MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
Drugs and Mode of Action
Drug(s) Desogestrel Drug Info Approved Hormonal contraceptives [536361], [542071]
Dydrogesterone Drug Info Approved Menstrual disorders [539904], [550691]
Estradiol valerate/dienogest Drug Info Approved Unspecified [551871]
Ethynodiol Diacetate Drug Info Approved Hormonal contraceptives [538500], [542078]
Etonogestrel Drug Info Approved Female contraception [536361], [542580]
Levonorgestrel Drug Info Approved Hormonal contraceptives [536361], [539908]
Medroxyprogesterone Drug Info Approved Cancer [551871]
Megestrol Drug Info Approved Advanced breast carcinoma; Advanced endometrium carcinoma [536165]
Norethindrone Drug Info Approved Cancer [551871]
Norgestimate Drug Info Approved Hormonal contraceptives [536361], [542097]
Norgestrel Drug Info Approved Contraception [538483], [551871]
Progesterone Drug Info Approved Premature labour [539513], [549497]
Ulipristal Drug Info Approved Contraception [531351]
Nestorone transdermal spray Drug Info Phase 3 Endometriosis [522001]
NPC-01 Drug Info Phase 3 Dysmenorrhea [523263]
Androgen restored contraceptive Drug Info Phase 2 Contraception [527054]
MK-8342 Drug Info Phase 2 Contraception [550004]
S-PRAnt Drug Info Phase 2 Uterine leiomyoma [549157]
Telapristone Drug Info Phase 2 Endometriosis [547243]
Tosagestin Drug Info Phase 2 Contraception [525775]
Vilaprisan Drug Info Phase 2 Endometriosis [525223]
Virexxa Drug Info Phase 2 Endometrial cancer [524647]
ONAPRISTONE Drug Info Phase 1/2 Contraception [524622], [539909]
PF-2413873 Drug Info Phase 1 Endometriosis [522505]
Asoprisnil Drug Info Discontinued in Phase 3 Endometriosis [536772], [539910]
Org-31710 Drug Info Discontinued in Phase 1 Contraception [545237]
BAY-39-9624 Drug Info Terminated Osteoporosis [547256]
RU-46556 Drug Info Terminated Endometrial cancer [545435]
Inhibitor 1-Benzyl-3-phenylquinazoline-2,4(1H,3H)-dione Drug Info [529568]
2,2,4-Trimethyl-6-phenyl-1,2-dihydro-quinoline Drug Info [534695]
2-(4-Amino-3'-chloro-biphenyl-3-yl)-propan-2-ol Drug Info [526276]
3,3-dimethyl-5-m-tolyl-2,3-dihydro-1H-inden-1-one Drug Info [530484]
3-(3,3-dimethyl-2-oxoindolin-5-yl)benzonitrile Drug Info [529352]
3-Phenyl-1-propylquinazoline-2,4(1H,3H)-dione Drug Info [529568]
4-(2,4-diethyl-1H-pyrrol-3-yloxy)benzonitrile Drug Info [530880]
5,N-Dihydroxythalidomide Drug Info [529568]
5-(2-oxoindolin-5-yl)-1H-pyrrole-2-carbonitrile Drug Info [529352]
6-(3-Nitro-phenyl)-3H-benzothiazol-2-one Drug Info [527672]
AL-43 Drug Info [526567]
GSK-1564023A Drug Info [530767]
GSK-325971A Drug Info [530767]
Lecanindole D Drug Info [530483]
LGD-5552 Drug Info [529166]
Methyltrienolone Drug Info [551393]
PF-02367982 Drug Info [530880]
Tanaproget Drug Info [551374]
WAY-255348 Drug Info [529352]
ZK-230211 Drug Info [525950]
Agonist Androgen restored contraceptive Drug Info [551483]
BAY-39-9624 Drug Info [551732]
Dydrogesterone Drug Info [536560]
GSK-008A Drug Info [543903]
Medroxyprogesterone Drug Info [536560]
MK-8342 Drug Info [543903]
Nestorone transdermal spray Drug Info [532946]
Norethindrone Drug Info [535980]
Norgestimate Drug Info [536305], [537309]
Norgestrel Drug Info [536668]
NPC-01 Drug Info [523263]
ORG2058 Drug Info [543903]
Progesterone Drug Info [551103]
Tosagestin Drug Info [527744]
[3H]ORG2058 Drug Info [543903]
Antagonist APR19 Drug Info [532304]
PF-2413873 Drug Info [550034]
S-PRAnt Drug Info [532387]
Telapristone Drug Info [527064]
Vilaprisan Drug Info [549227], [551871]
Modulator Asoprisnil Drug Info [536772]
Desogestrel Drug Info [535085]
Estradiol valerate/dienogest Drug Info [531351]
ONAPRISTONE Drug Info
Org-31710 Drug Info [526214]
RU-46556 Drug Info [533113]
SPRMs, oral, uterine fibroids, Tokai Pharmaceuticals Drug Info [543903]
Ulipristal Drug Info [531351]
ZK-112993 Drug Info
ZK-114043 Drug Info
ZK-136798 Drug Info
Binder Ethynodiol Diacetate Drug Info [537774], [537954]
Etonogestrel Drug Info [535188], [537309]
Levonorgestrel Drug Info [537153]
Megestrol Drug Info [535883]
Inducer Virexxa Drug Info [543903]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Oocyte meiosis
Progesterone-mediated oocyte maturation
Pathway Interaction Database Cellular roles of Anthrax toxin
Reactome Nuclear signaling by ERBB4
Nuclear Receptor transcription pathway
WikiPathways Ovarian Infertility Genes
Signaling by ERBB4
Nuclear Receptors
References
Ref 522001ClinicalTrials.gov (NCT00455156) Study of the Safety, Efficacy and Cycle Control of a Contraceptive Vaginal Ring. U.S. National Institutes of Health.
Ref 522505ClinicalTrials.gov (NCT00800618) A Study To Investigate How The Body Handles Multiple Doses Of PF-0243873 And To Investigate The Effect Of PF-02413873 On Sex Hormone Levels In Healthy Young Women. U.S. National Institutes of Health.
Ref 523263ClinicalTrials.gov (NCT01246791) Pharmacokinetics of NPC-01 After Single Oral Administration in Healthy Female Volunteers. U.S. National Institutes of Health.
Ref 524622ClinicalTrials.gov (NCT02049190) Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer. U.S. National Institutes of Health.
Ref 524647ClinicalTrials.gov (NCT02064725) Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA. U.S. National Institutes of Health.
Ref 525223ClinicalTrials.gov (NCT02465814) Assess Safety and Efficacy of Vilaprisan in Patients With Uterine Fibroids.
Ref 525775Excretion balance and metabolism of the progestagen Org 30659 in healthy postmenopausal women. J Steroid Biochem Mol Biol. 2000 May;73(1-2):39-48.
Ref 527054Treatment outcome in endodontics-the Toronto Study. Phase II: initial treatment. J Endod. 2004 May;30(5):302-9.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 536165Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7.
Ref 536361Natural 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 536772New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
Ref 538483FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017031.
Ref 538500FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018168.
Ref 539513(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: 2377).
Ref 539904(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: 2878).
Ref 539908(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: 2881).
Ref 539909(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: 2882).
Ref 539910(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: 2883).
Ref 542071(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: 7065).
Ref 542078(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: 7072).
Ref 542097(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: 7091).
Ref 542580(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: 7590).
Ref 545237Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002550)
Ref 545435Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003252)
Ref 547243Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014404)
Ref 547256Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014491)
Ref 549157Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033040)
Ref 549497Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038483)
Ref 550004Clinical pipeline report, company report or official report of Merck (May 7, 2015).
Ref 550691Drug information of Dydrogesterone, 2008. eduDrugs.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 523263ClinicalTrials.gov (NCT01246791) Pharmacokinetics of NPC-01 After Single Oral Administration in Healthy Female Volunteers. U.S. National Institutes of Health.
Ref 525950J Med Chem. 2000 Dec 28;43(26):5010-6.Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.
Ref 526214Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells. Fertil Steril. 2001 Dec;76(6):1225-31.
Ref 526276Bioorg Med Chem Lett. 2002 Mar 11;12(5):787-90.Potent nonsteroidal progesterone receptor agonists: synthesis and SAR study of 6-aryl benzoxazines.
Ref 526567J 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 527064In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol. 2004 Mar;88(3):277-88.
Ref 527672J Med Chem. 2005 Aug 11;48(16):5092-5.Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potentand selective nonsteroidal progesterone receptor agonist tanaproget.
Ref 527744Effects of progestins on the proliferation of estrogen-dependent human breast cancer cells under growth factor-defined conditions. J Steroid Biochem Mol Biol. 1992 Jun;42(5):457-65.
Ref 529166Proc 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 529352J 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 529568Bioorg Med Chem. 2008 Jul 15;16(14):7046-54. Epub 2008 May 10.Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton.
Ref 530483J Nat Prod. 2009 Nov;72(11):1944-8.The lecanindoles, nonsteroidal progestins from the terrestrial fungus Verticillium lecanii 6144.
Ref 530484Bioorg Med Chem Lett. 2009 Dec 1;19(23):6666-9. Epub 2009 Oct 7.5-Aryl indanones and derivatives as non-steroidal progesterone receptor modulators.
Ref 530767Bioorg Med Chem Lett. 2010 Apr 1;20(7):2340-3. Epub 2010 Feb 4.The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist.
Ref 530880Bioorg Med Chem Lett. 2010 Jun 1;20(11):3384-6. Epub 2010 Apr 13.Optimisation of a pyrazole series of progesterone antagonists; Part 1.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 532304A new strategy for selective targeting of progesterone receptor with passive antagonists. Mol Endocrinol. 2013 Jun;27(6):909-24.
Ref 532387BAY 1002670: a novel, highly potent and selective progesterone receptor modulator for gynaecological therapies. Hum Reprod. 2013 Aug;28(8):2253-64.
Ref 532946Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis. J Neuroimmunol. 2014 Nov 15;276(1-2):89-97.
Ref 533113New analogues of mifepristone with more dissociated antiprogesterone activities. J Steroid Biochem. 1989;34(1-6):413-7.
Ref 534695J Med Chem. 1998 Aug 27;41(18):3461-6.Discovery and preliminary SAR studies of a novel, nonsteroidal progesterone receptor antagonist pharmacophore.
Ref 535085Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
Ref 535188Endometrial effects of etonogestrel (Implanon) contraceptive implant. Curr Opin Obstet Gynecol. 2001 Jun;13(3):335-41.
Ref 535883Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
Ref 535980Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes. J Med Chem. 2004 Jun 17;47(13):3381-7.
Ref 536305A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65.
Ref 536560Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31.Epub 2007 Oct 22.
Ref 536668Toll-like receptor-4-mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors. Immunology. 2008 Sep;125(1):59-69. Epub 2008 Mar 28.
Ref 536772New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
Ref 537153Met909 plays a key role in the activation of the progesterone receptor and also in the high potency of 13-ethyl progestins. Mol Pharmacol. 2009 Jun;75(6):1317-24. Epub 2009 Mar 16.
Ref 537309Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
Ref 537774The place of progestational hormones in gynecological therapy. Ginekol Pol. 1970 May;41(5):497-502.
Ref 537954Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84.
Ref 543903(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: 627).
Ref 549227Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033939)
Ref 550034Unusual base-catalyzed exchange in the synthesis of deuterated PF-2413873. Journal of Labelled Compounds. 08/2009; 52(10):435 - 442.
Ref 551103Clinical pipeline report, company report or official report of lipocine.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551483Clinical pipeline report, company report or official report of Pantarhei Bioscience .
Ref 551732Bayer is seeking an exclusive licensee for its end-of-Phase I progestinagonist Bay 39-9624. Thepharmaletter. 29-04-2002.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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