Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUBKAZZ)

• DOT Name: Androgen receptor (AR)
• Synonyms: Dihydrotestosterone receptor; Nuclear receptor subfamily 3 group C member 4
• Gene Name: AR
• Related Disease:
  Androgen insensitivity syndrome
  Kennedy disease
  Partial androgen insensitivity syndrome
  Complete androgen insensitivity syndrome
• UniProt ID: ANDR_HUMAN
• PDB ID: 1E3G ; 1GS4 ; 1T5Z ; 1T63 ; 1T65 ; 1XJ7 ; 1XOW ; 1XQ3 ; 1Z95 ; 2AM9 ; 2AMA ; 2AMB ; 2AO6 ; 2AX6 ; 2AX7 ; 2AX8 ; 2AX9 ; 2AXA ; 2HVC ; 2OZ7 ; 2PIO ; 2PIP ; 2PIQ ; 2PIR ; 2PIT ; 2PIU ; 2PIV ; 2PIW ; 2PIX ; 2PKL ; 2PNU ; 2Q7I ; 2Q7J ; 2Q7K ; 2Q7L ; 2YHD ; 2YLO ; 2YLP ; 2YLQ ; 2Z4J ; 3B5R ; 3B65 ; 3B66 ; 3B67 ; 3B68 ; 3BTR ; 3L3X ; 3L3Z ; 3RLJ ; 3RLL ; 3V49 ; 3V4A ; 3ZQT ; 4HLW ; 4K7A ; 4OEA ; 4OED ; 4OEY ; 4OEZ ; 4OFR ; 4OFU ; 4OGH ; 4OH5 ; 4OH6 ; 4OHA ; 4OIL ; 4OIU ; 4OJ9 ; 4OJB ; 4OK1 ; 4OKB ; 4OKT ; 4OKW ; 4OKX ; 4OLM ; 4QL8 ; 5CJ6 ; 5JJM ; 5T8E ; 5T8J ; 5V8Q ; 5VO4 ; 7ZTX ; 7ZTZ ; 7ZU1 ; 7ZU2 ; 8E1A ; 8FGY ; 8FGZ ; 8FH0 ; 8FH1 ; 8FH2
• Pfam ID: PF02166 ; PF00104 ; PF00105
• Sequence:
  MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQ
  QQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQ
  SALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSAD
  LKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELC
  KAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAG
  KSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQ
  SRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAA
  GPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAP
  YGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRL
  ETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRN
  DCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKL
  TVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWA
  KALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSR
  MYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELD
  RIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEII
  SVQVPKILSGKVKPIYFHTQ
• 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 like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3; [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones; [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones.
• Tissue Specificity: .Mainly expressed in heart and skeletal muscle.; [Isoform 3]: Expressed in basal and stromal cells of the prostate (at protein level).
• KEGG Pathway:
  Oocyte meiosis (hsa04114)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Prostate cancer (hsa05215)
• Reactome Pathway:
  Nuclear Receptor transcription pathway (R-HSA-383280)
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886)
  Ub-specific processing proteases (R-HSA-5689880)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgen insensitivity syndrome	DISUZBBO	Definitive	X-linked	[1]
Kennedy disease	DISXZVM1	Definitive	X-linked	[2]
Partial androgen insensitivity syndrome	DISQ1113	Strong	X-linked	[3]
Complete androgen insensitivity syndrome	DISQL418	Supportive	X-linked	[4]

This DOT Affected the Drug Response of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bicalutamide	DMZMSPF	Approved	Androgen receptor (AR) decreases the response to substance of Bicalutamide.	[76]
Enzalutamide	DMGL19D	Approved	Androgen receptor (AR) decreases the response to substance of Enzalutamide.	[55]
Nifedipine	DMSVOZT	Approved	Androgen receptor (AR) increases the Gingival hyperplasia ADR of Nifedipine.	[77]
Prasterone	DM67VKL	Approved	Androgen receptor (AR) increases the response to substance of Prasterone.	[78]
Hydroxyflutamide	DMGIZF5	Approved	Androgen receptor (AR) increases the response to substance of Hydroxyflutamide.	[78]
ABIRATERONE	DM8V75C	Approved	Androgen receptor (AR) decreases the response to substance of ABIRATERONE.	[55]
Nilutamide	DMFN07X	Approved	Androgen receptor (AR) increases the response to substance of Nilutamide.	[78]
SB216763	DMIYFQ5	Investigative	Androgen receptor (AR) increases the response to substance of SB216763.	[79]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Androgen receptor (AR).	[5]

85 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Androgen receptor (AR).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Androgen receptor (AR).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Androgen receptor (AR).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Androgen receptor (AR).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Androgen receptor (AR).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Androgen receptor (AR).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Androgen receptor (AR).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Androgen receptor (AR).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Androgen receptor (AR).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Androgen receptor (AR).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Androgen receptor (AR).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of Androgen receptor (AR).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Androgen receptor (AR).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Androgen receptor (AR).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Androgen receptor (AR).	[20]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Androgen receptor (AR).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Androgen receptor (AR).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Androgen receptor (AR).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Androgen receptor (AR).	[23]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the activity of Androgen receptor (AR).	[24]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate increases the expression of Androgen receptor (AR).	[26]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the activity of Androgen receptor (AR).	[28]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the activity of Androgen receptor (AR).	[29]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Androgen receptor (AR).	[30]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Androgen receptor (AR).	[31]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the activity of Androgen receptor (AR).	[32]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Androgen receptor (AR).	[33]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the activity of Androgen receptor (AR).	[34]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Androgen receptor (AR).	[35]
Lindane	DMB8CNL	Approved	Lindane affects the expression of Androgen receptor (AR).	[36]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone affects the activity of Androgen receptor (AR).	[37]
Docetaxel	DMDI269	Approved	Docetaxel decreases the expression of Androgen receptor (AR).	[38]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Androgen receptor (AR).	[40]
Dutasteride	DMQ4TJK	Approved	Dutasteride increases the expression of Androgen receptor (AR).	[43]
Felodipine	DMOSW35	Approved	Felodipine increases the activity of Androgen receptor (AR).	[34]
Danazol	DML8KTN	Approved	Danazol increases the activity of Androgen receptor (AR).	[32]
Idarubicin	DMM0XGL	Approved	Idarubicin increases the activity of Androgen receptor (AR).	[34]
Nimodipine	DMQ0RKZ	Approved	Nimodipine decreases the activity of Androgen receptor (AR).	[34]
Nitrendipine	DM21C09	Approved	Nitrendipine decreases the activity of Androgen receptor (AR).	[34]
Nisoldipine	DM7ISKJ	Approved	Nisoldipine decreases the activity of Androgen receptor (AR).	[34]
Methyltestosterone	DMWLFGO	Approved	Methyltestosterone increases the activity of Androgen receptor (AR).	[44]
Ospemifene	DMC4GEI	Approved	Ospemifene decreases the expression of Androgen receptor (AR).	[45]
Hydroxyprogesterone	DMIKQH5	Approved	Hydroxyprogesterone increases the activity of Androgen receptor (AR).	[32]
Norgestimate	DMYP4XC	Approved	Norgestimate decreases the expression of Androgen receptor (AR).	[46]
Benidipine	DMWNP6B	Phase 4	Benidipine decreases the activity of Androgen receptor (AR).	[34]
Cyproterone acetate	DMLMOIJ	Phase 4	Cyproterone acetate decreases the expression of Androgen receptor (AR).	[46]
Lacidipine	DMQP5I3	Phase 4	Lacidipine increases the activity of Androgen receptor (AR).	[34]
Azelnidipine	DMA12HL	Phase 4	Azelnidipine decreases the activity of Androgen receptor (AR).	[34]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Androgen receptor (AR).	[47]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Androgen receptor (AR).	[48]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Androgen receptor (AR).	[49]
I3C	DMIGFOR	Phase 3	I3C decreases the activity of Androgen receptor (AR).	[50]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of Androgen receptor (AR).	[48]
Manidipine	DMJPGUA	Phase 3	Manidipine decreases the activity of Androgen receptor (AR).	[34]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Androgen receptor (AR).	[51]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the activity of Androgen receptor (AR).	[52]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Androgen receptor (AR).	[53]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of Androgen receptor (AR).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Androgen receptor (AR).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Androgen receptor (AR).	[55]
GSK2816126	DMJDVW4	Phase 1	GSK2816126 decreases the expression of Androgen receptor (AR).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Androgen receptor (AR).	[57]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the activity of Androgen receptor (AR).	[34]
KENPAULLONE	DMAGVXW	Patented	KENPAULLONE increases the activity of Androgen receptor (AR).	[58]
FORMESTANE	DMWIDJK	Withdrawn from market	FORMESTANE increases the expression of Androgen receptor (AR).	[60]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Androgen receptor (AR).	[53]
Organon	DMERWUC	Preclinical	Organon decreases the activity of Androgen receptor (AR).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Androgen receptor (AR).	[61]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Androgen receptor (AR).	[62]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Androgen receptor (AR).	[63]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Androgen receptor (AR).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Androgen receptor (AR).	[64]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the activity of Androgen receptor (AR).	[65]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the activity of Androgen receptor (AR).	[66]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Androgen receptor (AR).	[67]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Androgen receptor (AR).	[68]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Androgen receptor (AR).	[69]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Androgen receptor (AR).	[70]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the activity of Androgen receptor (AR).	[71]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the activity of Androgen receptor (AR).	[44]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the expression of Androgen receptor (AR).	[48]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE decreases the expression of Androgen receptor (AR).	[73]
Morin	DM2OGZ5	Investigative	Morin decreases the expression of Androgen receptor (AR).	[74]
Tetramethylbutylphenol	DMW9CH2	Investigative	Tetramethylbutylphenol decreases the activity of Androgen receptor (AR).	[44]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Androgen receptor (AR).	[54]

14 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Etoposide increases the degradation of Androgen receptor (AR).	[25]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the localization of Androgen receptor (AR).	[27]
Mitotane	DMU1GX0	Approved	Mitotane affects the binding of Androgen receptor (AR).	[39]
Exemestane	DM9HPW3	Approved	Exemestane affects the localization of Androgen receptor (AR).	[41]
Spironolactone	DM2AQ5N	Approved	Spironolactone affects the binding of Androgen receptor (AR).	[42]
Oxidized glutathione	DM9EQC0	Approved	Oxidized glutathione affects the localization of Androgen receptor (AR).	[41]
Drospirenone	DM1A9W3	Approved	Drospirenone affects the localization of Androgen receptor (AR).	[41]
Prulifloxacin	DMOK965	Approved	Prulifloxacin affects the localization of Androgen receptor (AR).	[41]
Gestrinone	DMP0OVQ	Approved	Gestrinone affects the localization of Androgen receptor (AR).	[41]
Ethynodiol diacetate	DMZM84R	Approved	Ethynodiol diacetate affects the localization of Androgen receptor (AR).	[41]
Glycyrrhizin	DM8M2N3	Phase 3	Glycyrrhizin affects the localization of Androgen receptor (AR).	[41]
PMID27841045-Compound-129	DME2IHD	Patented	PMID27841045-Compound-129 increases the degradation of Androgen receptor (AR).	[59]
	DM9CEI5		affects the binding of Androgen receptor (AR).	[72]
Ginsenoside RG3	DMFN58T	Investigative	Ginsenoside RG3 increases the degradation of Androgen receptor (AR).	[75]

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