Target General Infomation
Target ID
T22939 (Former ID: TTDS00245)
Target Name
Progesterone receptor (PGR)
Synonyms
PR; Nuclear receptor subfamily 3 group C member 3; NR3C3
Gene Name
PGR
Target Type
Successful target
[1]
Disease [+] 5 Target-related Diseases +
1 Breast cancer [ICD-11: 2C60-2C6Y]
2 Contraceptive management [ICD-11: QA21]
3 Menstrual cycle bleeding disorder [ICD-11: GA20]
4 Preterm labour/delivery [ICD-11: JB00]
5 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Function
Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
BioChemical Class
Nuclear hormone receptor
UniProt ID
PRGR_HUMAN
Sequence
MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
Drugs and Modes of Action
Approved Drug(s) [+] 13 Approved Drugs +
1 Desogestrel Drug Info Approved Contraception [2], [3]
2 Dydrogesterone Drug Info Approved Menstrual disorder [4], [5]
3 Estradiol valerate/dienogest Drug Info Approved Discovery agent [6]
4 Ethynodiol Diacetate Drug Info Approved Contraception [7], [8]
5 Etonogestrel Drug Info Approved Contraception [3], [9]
6 Levonorgestrel Drug Info Approved Contraception [3], [10]
7 Medroxyprogesterone Drug Info Approved Solid tumour/cancer [6]
8 Megestrol Drug Info Approved Breast cancer [11]
9 Norethindrone Drug Info Approved Solid tumour/cancer [6]
10 Norgestimate Drug Info Approved Contraception [3], [12]
11 Progesterone Drug Info Approved Premature labour [13], [14]
12 Segesterone acetate and ethinyl estradiol vaginal system Drug Info Approved Contraception [15]
13 Ulipristal Drug Info Approved Contraception [16]
Clinical Trial Drug(s) [+] 12 Clinical Trial Drugs +
1 Nestorone transdermal spray Drug Info Phase 3 Endometriosis [17]
2 NPC-01 Drug Info Phase 3 Dysmenorrhea [18]
3 Androgen restored contraceptive Drug Info Phase 2 Contraception [19]
4 BAY 86-5044 Drug Info Phase 2 Breast cancer [20]
5 MK-8342 Drug Info Phase 2 Contraception [21]
6 S-PRAnt Drug Info Phase 2 Uterine fibroids [22]
7 Telapristone Drug Info Phase 2 Endometriosis [23]
8 Tosagestin Drug Info Phase 2 Contraception [24]
9 Vilaprisan Drug Info Phase 2 Endometriosis [25]
10 Virexxa Drug Info Phase 2 Endometrial cancer [26]
11 ONAPRISTONE Drug Info Phase 1/2 Contraception [27], [28]
12 PF-2413873 Drug Info Phase 1 Endometriosis [29]
Discontinued Drug(s) [+] 4 Discontinued Drugs +
1 Asoprisnil Drug Info Discontinued in Phase 3 Endometriosis [30], [31]
2 Org-31710 Drug Info Discontinued in Phase 1 Contraception [32]
3 BAY-39-9624 Drug Info Terminated Osteoporosis [33]
4 RU-46556 Drug Info Terminated Endometrial cancer [34]
Mode of Action [+] 6 Modes of Action +
Modulator [+] 12 Modulator drugs +
1 Desogestrel Drug Info [35]
2 Estradiol valerate/dienogest Drug Info [16]
3 Segesterone acetate and ethinyl estradiol vaginal system Drug Info [15]
4 Ulipristal Drug Info [16]
5 ONAPRISTONE Drug Info [54]
6 Asoprisnil Drug Info [31]
7 Org-31710 Drug Info [56]
8 RU-46556 Drug Info [58]
9 SPRMs, oral, uterine fibroids, Tokai Pharmaceuticals Drug Info [49]
10 ZK-112993 Drug Info [72]
11 ZK-114043 Drug Info [73]
12 ZK-136798 Drug Info [74]
Agonist [+] 13 Agonist drugs +
1 Dydrogesterone Drug Info [36]
2 Medroxyprogesterone Drug Info [36]
3 Norethindrone Drug Info [44]
4 Norgestimate Drug Info [39], [45]
5 Progesterone Drug Info [1]
6 Nestorone transdermal spray Drug Info [46]
7 NPC-01 Drug Info [18]
8 Androgen restored contraceptive Drug Info [47]
9 MK-8342 Drug Info [49]
10 Tosagestin Drug Info [52]
11 BAY-39-9624 Drug Info [57]
12 GSK-008A Drug Info [49]
13 ORG2058 Drug Info [49]
Binder [+] 4 Binder drugs +
1 Ethynodiol Diacetate Drug Info [37], [38]
2 Etonogestrel Drug Info [39], [40]
3 Levonorgestrel Drug Info [41], [42]
4 Megestrol Drug Info [43]
Inhibitor [+] 20 Inhibitor drugs +
1 BAY 86-5044 Drug Info [48]
2 1-Benzyl-3-phenylquinazoline-2,4(1H,3H)-dione Drug Info [59]
3 2,2,4-Trimethyl-6-phenyl-1,2-dihydro-quinoline Drug Info [60]
4 2-(4-Amino-3'-chloro-biphenyl-3-yl)-propan-2-ol Drug Info [61]
5 3,3-dimethyl-5-m-tolyl-2,3-dihydro-1H-inden-1-one Drug Info [62]
6 3-(3,3-dimethyl-2-oxoindolin-5-yl)benzonitrile Drug Info [63]
7 3-Phenyl-1-propylquinazoline-2,4(1H,3H)-dione Drug Info [59]
8 4-(2,4-diethyl-1H-pyrrol-3-yloxy)benzonitrile Drug Info [64]
9 5,N-Dihydroxythalidomide Drug Info [59]
10 5-(2-oxoindolin-5-yl)-1H-pyrrole-2-carbonitrile Drug Info [63]
11 6-(3-Nitro-phenyl)-3H-benzothiazol-2-one Drug Info [65]
12 AL-43 Drug Info [66]
13 GSK-1564023A Drug Info [67]
14 GSK-325971A Drug Info [67]
15 Lecanindole D Drug Info [69]
16 LGD-5552 Drug Info [70]
17 PF-02367982 Drug Info [64]
18 Tanaproget Drug Info [71]
19 WAY-255348 Drug Info [63]
20 [3H]methyltrienolone Drug Info [75]
Antagonist [+] 5 Antagonist drugs +
1 S-PRAnt Drug Info [50]
2 Telapristone Drug Info [51]
3 Vilaprisan Drug Info [6], [53]
4 PF-2413873 Drug Info [55]
5 GTPL8662 Drug Info [68]
Inducer [+] 1 Inducer drugs +
1 Virexxa Drug Info [49]
Target Regulators
Target-regulating microRNAs
Target-regulating Transcription Factors
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 2 KEGG Pathways +
1 Oocyte meiosis
2 Progesterone-mediated oocyte maturation
PID Pathway [+] 1 PID Pathways +
1 Cellular roles of Anthrax toxin
Reactome [+] 2 Reactome Pathways +
1 Nuclear signaling by ERBB4
2 Nuclear Receptor transcription pathway
WikiPathways [+] 3 WikiPathways +
1 Ovarian Infertility Genes
2 Signaling by ERBB4
3 Nuclear Receptors
Target-Related Models and Studies
Target Validation
References
REF 1 Clinical pipeline report, company report or official report of lipocine.
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: 7065).
REF 3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
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: 2878).
REF 5 Drug information of Dydrogesterone, 2008. eduDrugs.
REF 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 7 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: 7072).
REF 8 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018168.
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: 7590).
REF 10 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: 2881).
REF 11 Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7.
REF 12 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: 7091).
REF 13 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: 2377).
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 800038483)
REF 15 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
REF 16 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
REF 17 ClinicalTrials.gov (NCT00455156) Study of the Safety, Efficacy and Cycle Control of a Contraceptive Vaginal Ring. U.S. National Institutes of Health.
REF 18 ClinicalTrials.gov (NCT01246791) Pharmacokinetics of NPC-01 After Single Oral Administration in Healthy Female Volunteers. U.S. National Institutes of Health.
REF 19 Treatment outcome in endodontics-the Toronto Study. Phase II: initial treatment. J Endod. 2004 May;30(5):302-9.
REF 20 ClinicalTrials.gov (NCT00555919) ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer. U.S. National Institutes of Health.
REF 21 Clinical pipeline report, company report or official report of Merck (May 7, 2015).
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 800033040)
REF 23 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014404)
REF 24 Excretion 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 25 ClinicalTrials.gov (NCT02465814) Assess Safety and Efficacy of Vilaprisan in Patients With Uterine Fibroids.
REF 26 ClinicalTrials.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 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. (Ligand id: 2882).
REF 28 ClinicalTrials.gov (NCT02049190) Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer. U.S. National Institutes of Health.
REF 29 ClinicalTrials.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 30 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: 2883).
REF 31 New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
REF 32 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002550)
REF 33 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014491)
REF 34 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003252)
REF 35 Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
REF 36 Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
REF 37 Contribution 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 38 The place of progestational hormones in gynecological therapy. Ginekol Pol. 1970 May;41(5):497-502.
REF 39 Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
REF 40 Endometrial effects of etonogestrel (Implanon) contraceptive implant. Curr Opin Obstet Gynecol. 2001 Jun;13(3):335-41.
REF 41 Met909 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.
REF 42 Toll-like receptor-4-mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors. Immunology. 2008 Sep;125(1):59-69.
REF 43 Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
REF 44 Progesterone 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 45 A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65.
REF 46 Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis. J Neuroimmunol. 2014 Nov 15;276(1-2):89-97.
REF 47 Clinical pipeline report, company report or official report of Pantarhei Bioscience .
REF 48 Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J Med Chem. 2000 Dec 28;43(26):5010-6.
REF 49 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: 627).
REF 50 BAY 1002670: a novel, highly potent and selective progesterone receptor modulator for gynaecological therapies. Hum Reprod. 2013 Aug;28(8):2253-64.
REF 51 In 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 52 Effects 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 53 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033939)
REF 54 Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer. 1999 Feb;35(2):214-8.
REF 55 Unusual base-catalyzed exchange in the synthesis of deuterated PF-2413873. Journal of Labelled Compounds. 08/2009; 52(10):435 - 442.
REF 56 Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells. Fertil Steril. 2001 Dec;76(6):1225-31.
REF 57 Bayer is seeking an exclusive licensee for its end-of-Phase I progestinagonist Bay 39-9624. Thepharmaletter. 29-04-2002.
REF 58 New analogues of mifepristone with more dissociated antiprogesterone activities. J Steroid Biochem. 1989;34(1-6):413-7.
REF 59 Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton. Bioorg Med Chem. 2008 Jul 15;16(14):7046-54.
REF 60 Discovery and preliminary SAR studies of a novel, nonsteroidal progesterone receptor antagonist pharmacophore. J Med Chem. 1998 Aug 27;41(18):3461-6.
REF 61 Potent nonsteroidal progesterone receptor agonists: synthesis and SAR study of 6-aryl benzoxazines. Bioorg Med Chem Lett. 2002 Mar 11;12(5):787-90.
REF 62 5-Aryl indanones and derivatives as non-steroidal progesterone receptor modulators. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6666-9.
REF 63 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.
REF 64 Optimisation of a pyrazole series of progesterone antagonists; Part 1. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3384-6.
REF 65 Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading... J Med Chem. 2005 Aug 11;48(16):5092-5.
REF 66 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 67 The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2340-3.
REF 68 A new strategy for selective targeting of progesterone receptor with passive antagonists. Mol Endocrinol. 2013 Jun;27(6):909-24.
REF 69 The lecanindoles, nonsteroidal progestins from the terrestrial fungus Verticillium lecanii 6144. J Nat Prod. 2009 Nov;72(11):1944-8.
REF 70 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 71 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 72 Tumor-inhibiting potential of ZK 112.993, a new progesterone antagonist, in hormone-sensitive, experimental rodent and human mammary tumors.Anticancer Res.1990 May-Jun;10(3):683-7.
REF 73 Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts. J Endocrinol. 1998 Sep;158(3):401-7.
REF 74 The antiovulatory activity of progesterone antagonists is not correlated to their antiprogestational potency in the rat. J Steroid Biochem Mol Biol. 1996 Sep;59(1):75-82.
REF 75 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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