Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUV8G9)

• DTT Name: Progesterone receptor (PGR)
• Synonyms: PR; Nuclear receptor subfamily 3 group C member 3; NR3C3
• Gene Name: PGR
• DTT Type: Successful target; [1]
• Related Disease:
  Breast cancer [ICD-11: 2C60-2C6Y]
  Contraceptive management [ICD-11: QA21]
  Menstrual cycle bleeding disorder [ICD-11: GA20]
  Preterm labour/delivery [ICD-11: JB00]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: PRGR_HUMAN
• TTD ID: T22939
• Sequence:
  MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
  PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
  PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
  AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
  PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
  MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
  CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
  PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
  KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
  YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
  YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
  GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
  LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
  DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
  FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
  LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
• 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.
• Reactome Pathway:
  Nuclear Receptor transcription pathway (R-HSA-383280)
  Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desogestrel	DM27U4Y	Contraception	QA21	Approved	[2]
Dydrogesterone	DMAKIDV	Menstrual disorder	GA20.3	Approved	[3]
Estradiol valerate/dienogest	DMLNMEA	Discovery agent	N.A.	Approved	[4]
Ethynodiol diacetate	DMZM84R	Contraception	QA21	Approved	[5], [6]
Etonogestrel	DMKA8J4	Contraception	QA21	Approved	[7], [8]
Levonorgestrel	DM1DP7T	Contraception	QA21	Approved	[9], [10]
Medroxyprogesterone	DMBGWPH	Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Megestrol	DMDH9KX	Breast cancer	2C60-2C65	Approved	[11]
Norethindrone	DMTY169	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Norgestimate	DMYP4XC	Contraception	QA21	Approved	[7], [13]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[1]
Segesterone acetate; ethinyl estradiol	DMFEGB0	Contraception	QA21	Approved	[14]
Ulipristal	DMBNI20	Contraception	QA21	Approved	[4]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nestorone	DMVP7HI	Endometriosis	GA10	Phase 3	[15]
NPC-01	DMMC3Y8	Dysmenorrhea	GA34.3	Phase 3	[16]
BAY 86-5044	DMRZLU4	Breast cancer	2C60-2C65	Phase 2	[17]
MK-8342	DMD6E5W	Contraception	QA21	Phase 2	[18]
Onapristone	DMT6E5N	Breast cancer	2C60-2C65	Phase 2	[19]
S-PRAnt	DMFAO5G	Uterine fibroids	2E86.0	Phase 2	[20]
Telapristone	DM9AWSO	Endometriosis	GA10	Phase 2	[21]
Tosagestin	DM2HDTM	Contraception	QA21	Phase 2	[22]
Vilaprisan	DME7VZD	Endometriosis	GA10	Phase 2	[23], [24]
Virexxa	DMEXMV5	Endometrial cancer	2C76	Phase 2	[18]
PF-2413873	DMCOUHT	Endometriosis	GA10	Phase 1	[25]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Asoprisnil	DM4BV2W	Endometriosis	GA10	Discontinued in Phase 3	[26]
Org-31710	DMZKTU5	Contraception	QA21	Discontinued in Phase 1	[27]
BAY-39-9624	DMPUG18	Osteoporosis	FB83.0	Terminated	[28]
RU-46556	DM8B1DH	Endometrial cancer	2C76	Terminated	[29]

25 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-Benzyl-3-phenylquinazoline-2,4(1H,3H)-dione	DMV7UC0	Discovery agent	N.A.	Investigative	[30]
2,2,4-Trimethyl-6-phenyl-1,2-dihydro-quinoline	DMP9ECK	Discovery agent	N.A.	Investigative	[31]
2-(4-Amino-3'-chloro-biphenyl-3-yl)-propan-2-ol	DMSHPCW	Discovery agent	N.A.	Investigative	[32]
3,3-dimethyl-5-m-tolyl-2,3-dihydro-1H-inden-1-one	DMUS0A4	Discovery agent	N.A.	Investigative	[33]
3-(3,3-dimethyl-2-oxoindolin-5-yl)benzonitrile	DMSHORK	Discovery agent	N.A.	Investigative	[34]
3-Phenyl-1-propylquinazoline-2,4(1H,3H)-dione	DMEG3YX	Discovery agent	N.A.	Investigative	[30]
4-(2,4-diethyl-1H-pyrrol-3-yloxy)benzonitrile	DMBLAI1	Discovery agent	N.A.	Investigative	[35]
5,N-Dihydroxythalidomide	DM3MSZN	Discovery agent	N.A.	Investigative	[30]
5-(2-oxoindolin-5-yl)-1H-pyrrole-2-carbonitrile	DMR7OHB	Discovery agent	N.A.	Investigative	[34]
6-(3-Nitro-phenyl)-3H-benzothiazol-2-one	DM83VN6	Discovery agent	N.A.	Investigative	[36]
AL-43	DMLEDHR	Discovery agent	N.A.	Investigative	[37]
GSK-008A	DMC2ZF6	Gynecological disease	GA6Z	Investigative	[18]
GSK-1564023A	DMKN76P	Discovery agent	N.A.	Investigative	[38]
GSK-325971A	DM1865H	Discovery agent	N.A.	Investigative	[38]
GTPL8662	DMZQETV	Discovery agent	N.A.	Investigative	[39]
Lecanindole D	DMZ7OHP	Discovery agent	N.A.	Investigative	[40]
LGD-5552	DM67KWM	Discovery agent	N.A.	Investigative	[41]
ORG2058	DMH1M6N	Discovery agent	N.A.	Investigative	[18]
PF-02367982	DMZ5JNT	Endometriosis	GA10	Investigative	[35]
Tanaproget	DMQCW7V	Estrogen deficiency	FB83.0Y	Investigative	[42]
WAY-255348	DMSLNWA	Solid tumour/cancer	2A00-2F9Z	Investigative	[34]
ZK-112993	DM8JN45	Discovery agent	N.A.	Investigative	[43]
ZK-114043	DMBCPKE	Discovery agent	N.A.	Investigative	[44]
ZK-136798	DMCQYBE	Discovery agent	N.A.	Investigative	[45]
[3H]methyltrienolone	DMTSGOW	Discovery agent	N.A.	Investigative	[46]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Endometriosis	GA10	Endometrium tissue	1.71E-02	-1.47	-0.86
Osteoporosis	FA20	Bone marrow	5.03E-02	0.19	1.3
Uterine cancer	2C82	Endometrium tissue	3.26E-38	-3.79	-2.5
Preterm birth	KA21.4Z	Myometrium	5.89E-01	-0.03	-0.05

References

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