Target General Infomation
Target ID
T46521
Former ID
TTDC00332
Target Name
mRNA of androgen receptor
Gene Name
AR
Synonyms
mRNA of Dihydrotestosterone receptor; mRNA of Nuclear receptor subfamily 3 group C member 4; AR
Target Type
Clinical Trial
Disease Acne vulgaris [ICD9: 706.1; ICD10: L70.0]
Atherosclerosis [ICD9: 414.0, 440; ICD10: I70]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Prostate cancer [ICD9: 185; ICD10: C61]
Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
BioChemical Class
Target of antisense drug
Target Validation
T46521
UniProt ID
Sequence
MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQ
QQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQ
SALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSAD
LKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELC
KAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAG
KSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQ
SRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAA
GPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAP
YGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRL
ETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRN
DCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKL
TVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWA
KALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSR
MYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELD
RIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEII
SVQVPKILSGKVKPIYFHTQ
Drugs and Mode of Action
Drug(s) EZN-4176 Drug Info Phase 1 Prostate cancer [551623]
ISIS-AR Drug Info Phase 1 Prostate cancer [551936]
RU-58841 Drug Info Discontinued in Phase 1 Acne vulgaris [546035]
Inhibitor 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane Drug Info [528558]
2'-Hydroxy-3-methoxy-biphenyl-4-carbonitrile Drug Info [529750]
2-chloro-4-(o-tolyloxy)benzonitrile Drug Info [530022]
2-methoxy-4-(2-methoxyphenylthio)benzonitrile Drug Info [529954]
2-methoxy-4-(m-tolyloxy)benzonitrile Drug Info [529954]
2-methoxy-4-(o-tolyloxy)benzonitrile Drug Info [529954]
2-methoxy-4-(p-tolyloxy)benzonitrile Drug Info [529954]
2-methoxy-4-(propylthio)benzonitrile Drug Info [529954]
3,2'-bis-trifluoromethyl-biphenyl-4-carbonitrile Drug Info [529009]
3-chloro-4-(o-tolyloxy)benzonitrile Drug Info [530022]
3-chloro-4-(o-tolylthio)benzonitrile Drug Info [529954]
3-methoxy-4-(m-tolyloxy)benzonitrile Drug Info [529954]
3-methoxy-4-(o-tolyloxy)benzonitrile Drug Info [529954]
3-methoxy-4-(p-tolyloxy)benzonitrile Drug Info [529954]
4-(2,6-dimethylphenylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(butylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
4-(butylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(cyclobutylmethylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(cyclopropylmethylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(isopentylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
4-(isopentylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(isopropylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
4-(isopropylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(m-tolyloxy)-2-(trifluoromethyl)benzonitrile Drug Info [530022]
4-(mesityloxy)-2-(trifluoromethyl)benzonitrile Drug Info [530022]
4-(mesitylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
4-(mesitylthio)-2-methoxybenzonitrile Drug Info [529954]
4-(o-tolyloxy)-2-(trifluoromethyl)benzonitrile Drug Info [530022]
4-(o-tolylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
4-(p-tolyloxy)-2-(trifluoromethyl)benzonitrile Drug Info [530022]
4-(propylthio)-2-(trifluoromethyl)benzonitrile Drug Info [529954]
5-Methoxyflavone Drug Info [530256]
6-amino-4-trifluoromethylquinolin-2(1H)-one Drug Info [528470]
6-Hydroxyflavanone Drug Info [530256]
6-N-propyl -4-trifluoromethylquinolin-2(1H)-one Drug Info [528470]
AL-43 Drug Info [526567]
APIGENIN Drug Info [530256]
BMS-564929 Drug Info [530061]
CP-394531 Drug Info [526345]
CP-409069 Drug Info [526345]
EPIERENONE Drug Info [529171]
EUGENOL Drug Info [530785]
KAEMPFEROL Drug Info [530256]
LG-120838 Drug Info [534728]
LG-121071 Drug Info [528792]
LGD-2226 Drug Info [528648]
LGD-5552 Drug Info [529166]
NSC-19028 Drug Info [530256]
NSC-26745 Drug Info [530256]
PF-0998425 Drug Info [529750]
RU-43044 Drug Info [526345]
RU-56187 Drug Info [530839]
RU-58841 Drug Info [529750]
WAY-252623 Drug Info [529781]
WAY-255348 Drug Info [529352]
YM-175735 Drug Info [527978]
ZK-230211 Drug Info [525950]
Agonist andarine Drug Info [530128]
[3H]dihydrotestosterone Drug Info [543904]
[3H]methyltrienolone Drug Info [543904]
[3H]mibolerone Drug Info [543904]
Antagonist bisphenol A Drug Info [532398]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Oocyte meiosis
Pathways in cancer
Prostate cancer
NetPath Pathway EGFR1 Signaling Pathway
AndrogenReceptor Signaling Pathway
FSH Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Coregulation of Androgen receptor activity
Regulation of Androgen receptor activity
Nongenotropic Androgen signaling
Regulation of nuclear beta catenin signaling and target gene transcription
FOXA1 transcription factor network
Notch-mediated HES/HEY network
Reactome Nuclear Receptor transcription pathway
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
WikiPathways SIDS Susceptibility Pathways
Integrated Pancreatic Cancer Pathway
Prostate Cancer
Integrated Breast Cancer Pathway
Nuclear Receptors
Androgen receptor signaling pathway
References
Ref 546035Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005990)
Ref 5516232011 Pipeline of Santaris Pharma.
Ref 551936Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
Ref 525950J Med Chem. 2000 Dec 28;43(26):5010-6.Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.
Ref 526345J Med Chem. 2002 Jun 6;45(12):2417-24.Discovery of potent, nonsteroidal, and highly selective glucocorticoid receptor antagonists.
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 527978J Med Chem. 2006 Jan 26;49(2):716-26.(+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3- yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist.
Ref 528470J Med Chem. 2006 Oct 19;49(21):6143-6.Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator.
Ref 528558J Med Chem. 2006 Dec 14;49(25):7366-72.Identification of the brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane as an androgen agonist.
Ref 528648Bioorg Med Chem Lett. 2007 Mar 15;17(6):1527-31. Epub 2007 Jan 8.Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones.
Ref 528792J Med Chem. 2007 May 17;50(10):2486-96. Epub 2007 Apr 17.Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.
Ref 529009Bioorg Med Chem Lett. 2007 Oct 15;17(20):5529-32. Epub 2007 Aug 19.Preparation of 4-aryl-2-trifluoromethylbenzonitrile derivatives as androgen receptor antagonists for topical suppression of sebum production.
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 529171J 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 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 529750J Med Chem. 2008 Nov 13;51(21):7010-4. Epub 2008 Oct 16.Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen receptor antagonist devoid of phototoxicity for dermatological indications.
Ref 529781J Med Chem. 2008 Nov 27;51(22):7161-8.Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesis.
Ref 529954Bioorg Med Chem Lett. 2009 Mar 1;19(5):1310-3. Epub 2009 Jan 27.4-(Alkylthio)- and 4-(arylthio)-benzonitrile derivatives as androgen receptor antagonists for the topical suppression of sebum production.
Ref 530022Bioorg Med Chem Lett. 2009 Apr 15;19(8):2176-8. Epub 2009 Mar 3.Diphenyl ethers as androgen receptor antagonists for the topical suppression of sebum production.
Ref 530061J Med Chem. 2009 May 14;52(9):2794-8.N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation.
Ref 530128Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J Med Chem. 2009 Jun 25;52(12):3597-617.
Ref 530256Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10. Epub 2009 Jun 23.Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay.
Ref 530785Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4. Epub 2010 Feb 21.Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay.
Ref 530839Bioorg Med Chem. 2010 May 1;18(9):3159-68. Epub 2010 Mar 19.Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists.
Ref 532398Structure-activity relationships of bisphenol A analogs at estrogen receptors (ERs): discovery of an ERalpha-selective antagonist. Bioorg Med Chem Lett. 2013 Jul 15;23(14):4031-6.
Ref 534728J 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 543904(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: 628).
Ref 5516232011 Pipeline of Santaris Pharma.
Ref 551942Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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