Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTS64P2)

• DTT Name: Androgen receptor (AR)
• Synonyms: Testosterone receptor; Nuclear receptor subfamily 3 group C member 4; NR3C4; Dihydrotestosterone receptor; DHTR
• Gene Name: AR
• DTT Type: Successful target; [1]
• Related Disease:
  Acne vulgaris [ICD-11: ED80]
  Acute myeloid leukaemia [ICD-11: 2A60]
  Alcoholic liver disease [ICD-11: DB94]
  Breast cancer [ICD-11: 2C60-2C6Y]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Female pelvic pain [ICD-11: GA34]
  Hypo-osmolality/hyponatraemia [ICD-11: 5C72]
  Low bone mass disorder [ICD-11: FB83]
  Mammary tumour [ICD-11: 2C60-2C6Z]
  Prostate cancer [ICD-11: 2C82]
  Testicular dysfunction [ICD-11: 5A81]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: ANDR_HUMAN
• TTD ID: T11211
• Sequence:
  MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQ
  QQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQ
  SALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSAD
  LKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELC
  KAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAG
  KSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQ
  SRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAA
  GPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAP
  YGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRL
  ETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRN
  DCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKL
  TVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWA
  KALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSR
  MYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELD
  RIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEII
  SVQVPKILSGKVKPIYFHTQ
• Function: 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. Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
• KEGG Pathway:
  Oocyte meiosis (hsa04114)
  Pathways in cancer (hsa05200)
  Prostate cancer (hsa05215)
• Reactome Pathway:
  Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

19 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arn-509	DMT81LZ	Acute myeloid leukaemia	2A60	Approved	[2]
Bicalutamide	DMZMSPF	Prostate cancer	2C82.0	Approved	[3], [1]
Clascoterone	DMPGR1E	Acne vulgaris	ED80	Approved	[4]
Cyproterone	DMQXLD2	Prostate cancer	2C82.0	Approved	[5]
Darolutamide	DMV7YFT	Prostate cancer	2C82.0	Approved	[6]
Dromostanolone	DMF2JDG	Mammary tumour	2C60-2C6Z	Approved	[7], [8]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[9]
Ethylestrenol	DM20VMW	Testosterone deficiency	5A81.1	Approved	[10]
Fludrocortisone	DMUDIR8	Cerebral salt-wasting syndrome	5C72	Approved	[11]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[12]
Fluoxymesterone	DMUHCF1	Breast cancer	2C60-2C65	Approved	[13], [14]
Flutamide	DMK0O7U	Prostate cancer	2C82.0	Approved	[1]
Hydroxyflutamide	DMGIZF5	Prostate cancer	2C82.0	Approved	[15], [16], [17]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[18]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[19]
Oxandrolone	DMU9MYJ	Alcoholic hepatitis	DB94.1	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[21]
Testosterone	DM7HUNW	Osteoporosis	FB83.0	Approved	[22], [23]
Dihydrotestosterone	DM3S8XC	Prostate hyperplasia	GA90	Phase 4	[24]

21 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HC-1119	DMB06MU	Prostate cancer	2C82.0	Phase 3	[25]
ZANOTERONE	DM9HUYP	Prostate hyperplasia	GA90	Phase 3	[26]
ASC-J9	DMDQS4W	End-stage renal disease	GB61.5	Phase 2	[27]
ASCJ-9	DMMBVCJ	Acne vulgaris	ED80	Phase 2	[28]
AZD5312	DMJ8V3K	Prostate cancer	2C82.0	Phase 2	[29]
MK-0773	DM2CJB4	Osteoporosis	FB83.0	Phase 2	[30]
Testogen TDS	DMMK6IT	Hypogonadism	5A61.0	Phase 2	[31]
TOK-001	DMVJWPR	Prostate cancer	2C82.0	Phase 2	[32]
APC-100	DM71I53	Prostate cancer	2C82.0	Phase 1/2	[33]
ARV-110	DMYCID5	Prostate cancer	2C82.0	Phase 1/2	[34]
ARV-471	DM276Y8	Breast cancer	2C60-2C65	Phase 1/2	[35]
ONC1-13B	DM2DHJS	Prostate cancer	2C82.0	Phase 1/2	[36]
AZD-3514	DMC1BXV	Prostate cancer	2C82.0	Phase 1	[37]
CC-94676	DM4581B	Invasive prostate cancer	2C82	Phase 1	[38]
Drug 2881078	DMWXQC9	Heart failure	BD10-BD13	Phase 1	[39]
DT-200	DMYFOJQ	Duchenne dystrophy	8C70	Phase 1	[40]
EPI-7386	DMUFN29	Prostate cancer	2C82.0	Phase 1	[41]
PS-178990	DM2594H	Muscle atrophy	FB32.Y	Phase 1	[42]
RAD-140	DMNVDI2	Breast cancer	2C60-2C65	Phase 1	[43]
TAS3681	DMFG6ML	Prostate cancer	2C82.0	Phase 1	[44]
TESTOSTERONE BUCICLATE	DM3DUHL	Contraception	QA21	Phase 1	[31]

11 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GW-275919	DMOIL29	Pain	MG30-MG3Z	Discontinued in Phase 2	[45]
HE-2000	DMWH4CY	Cystic fibrosis	CA25	Discontinued in Phase 2	[46]
NP-619	DM50PZH	Alopecia	ED70	Discontinued in Phase 2	[47]
Testosterone glucoside	DM5O6HM	Hypogonadism	5A61.0	Discontinued in Phase 2	[31]
GSK2849466	DMM7Q3L	Heart failure	BD10-BD13	Discontinued in Phase 1	[48]
LGD2941	DM9LEGU	Osteoporosis	FB83.0	Discontinued in Phase 1	[49]
MX-4509	DMC4RK7	Neurological disorder	6B60	Discontinued in Phase 1	[17]
Opterone	DMPDJC8	Hormone deficiency	5A61.1	Discontinued in Phase 1	[31]
PF-06260414	DMSE3WP	Cachexia	MG20	Discontinued in Phase 1	[50]
LG-2293	DMNXKR2	Prostate cancer	2C82.0	Terminated	[52]
ZD-3980	DM91IPH	Prostate hyperplasia	GA90	Terminated	[53]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GLPG-0492	DMSW07R	Cachexia	MG20	Preclinical	[51]

25 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane	DMDJYHK	Discovery agent	N.A.	Investigative	[54]
11-methyl-6,11-dihydro-5H-benzo[a]carbazol-9-ol	DM9IHFY	Discovery agent	N.A.	Investigative	[55]
6,11-dihydrothiochromeno[4,3-b]indol-8-ol	DM0RB53	Discovery agent	N.A.	Investigative	[55]
Andromustine	DMHL0ID	Prostate cancer	2C82.0	Investigative	[56]
ARN34	DMMCFEX	Discovery agent	N.A.	Investigative	[16]
ASC-JMX2	DMYJ87C	Prostate hyperplasia	GA90	Investigative	[56]
ASC-JMZ1	DMT5LJN	Bladder cancer	2C94	Investigative	[56]
Boldenone	DM0EKO5	Discovery agent	N.A.	Investigative	[57]
Calusterone	DMBK2S8	Discovery agent	N.A.	Investigative	[58]
CH-4933468	DM1ZF3Y	Prostate cancer	2C82.0	Investigative	[56]
Delta1-dihydrotestosterone	DML6MVH	Discovery agent	N.A.	Investigative	[59]
DL-3	DME9ODX	Prostate cancer	2C82.0	Investigative	[56]
EPI-001	DMYWV81	Prostate cancer	2C82.0	Investigative	[60]
GTx-027	DM315VL	Solid tumour/cancer	2A00-2F9Z	Investigative	[61]
HYG-440	DM7XISZ	Dermatological disease	DA24.Y	Investigative	[62]
OXENDLONE	DM6RJOI	Discovery agent	N.A.	Investigative	[63]
Palodesangren C	DMKLVSO	Discovery agent	N.A.	Investigative	[63]
Palodesangren D	DMY6NRC	Discovery agent	N.A.	Investigative	[63]
Palodesangren E	DMUEK1N	Discovery agent	N.A.	Investigative	[63]
RU-59063	DM5D9UT	Discovery agent	N.A.	Investigative	[64]
SARMs	DMILBO9	Solid tumour/cancer	2A00-2F9Z	Investigative	[56]
SX-ARPC	DMEA36L	Prostate cancer	2C82.0	Investigative	[65]
Testetrol	DMQDVNZ	Hypogonadism	5A61.0	Investigative	[66]
[3H]methyltrienolone	DMTSGOW	Discovery agent	N.A.	Investigative	[57]
[3H]mibolerone	DM6HDKQ	Discovery agent	N.A.	Investigative	[64]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alopecia	EA90	Skin from scalp	5.97E-06	0.25	0.78
Prostate cancer	2C82	Prostate	4.81E-01	-0.23	-0.29
Osteoporosis	FA20	Bone marrow	6.77E-02	0.76	2.2
Myopathy	8A00.0	Muscle tissue	2.13E-01	-0.07	-0.11
Atopic dermatitis	EA90	Skin	7.61E-08	-0.59	-2.99
Bladder cancer	2C82	Bladder tissue	4.00E-13	-1.62	-8.45

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