Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZLYR3)

• DOT Name: Angiotensinogen (AGT)
• Synonyms: Serpin A8) -angiotensin II); Angiotensin-4 (Angiotensin 3-8; Angiotensin IV; Ang IV); Angiotensin 1-9; Angiotensin 1-7; Angiotensin 1-5; Angiotensin 1-4]
• Gene Name: AGT
• Related Disease: Renal tubular dysgenesis of genetic origin
• UniProt ID: ANGT_HUMAN
• PDB ID: 1N9U; 1N9V; 2JP8; 2WXW; 2X0B; 3CK0; 3WOO; 3WOR; 4AA1; 4APH; 4FYS; 5E2Q; 5M3X; 5M3Y; 5XJM; 6I3F; 6I3I; 6JOD; 6OS0; 7C6A
• Pfam ID: PF00079
• Sequence:
  MAPAGVSLRATILCLLAWAGLAAGDRVYIHPFHLVIHNESTCEQLAKANAGKPKDPTFIP
  APIQAKTSPVDEKALQDQLVLVAAKLDTEDKLRAAMVGMLANFLGFRIYGMHSELWGVVH
  GATVLSPTAVFGTLASLYLGALDHTADRLQAILGVPWKDKNCTSRLDAHKVLSALQAVQG
  LLVAQGRADSQAQLLLSTVVGVFTAPGLHLKQPFVQGLALYTPVVLPRSLDFTELDVAAE
  KIDRFMQAVTGWKTGCSLMGASVDSTLAFNTYVHFQGKMKGFSLLAEPQEFWVDNSTSVS
  VPMLSGMGTFQHWSDIQDNFSVTQVPFTESACLLLIQPHYASDLDKVEGLTFQQNSLNWM
  KKLSPRTIHLTMPQLVLQGSYDLQDLLAQAELPAILHTELNLQKLSNDRIRVGEVLNSIF
  FELEADEREPTESTQQLNKPEVLEVTLNRPFLFAVYDQSATALHFLGRVANPLSTA
• Function: Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis; [Angiotensin-2]: Acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone. Acts by binding to angiotensin receptors AGTR1 and AGTR2. Also binds the DEAR/FBXW7-AS1 receptor; [Angiotensin-3]: Stimulates aldosterone release; [Angiotensin 1-7]: Is a ligand for the G-protein coupled receptor MAS1. Has vasodilator and antidiuretic effects. Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• Reactome Pathway:
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
  Peptide ligand-binding receptors (R-HSA-375276)
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Renal tubular dysgenesis of genetic origin	DISIP4Y5	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Angiotensinogen (AGT) decreases the response to substance of Temozolomide.	[46]
DTI-015	DMXZRW0	Approved	Angiotensinogen (AGT) decreases the response to substance of DTI-015.	[46]
Phenylephrine	DMZHUO5	Approved	Angiotensinogen (AGT) increases the response to substance of Phenylephrine.	[49]
Celiprolol	DMYTGW0	Phase 4	Angiotensinogen (AGT) affects the response to substance of Celiprolol.	[51]
6-Benzyloxy-9H-purin-2-ylamine	DMFI7A8	Investigative	Angiotensinogen (AGT) decreases the response to substance of 6-Benzyloxy-9H-purin-2-ylamine.	[46]

This DOT Affected the Regulation of Drug Effects of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Angiotensinogen (AGT) decreases the secretion of Progesterone.	[47]
Hydrocortisone	DMGEMB7	Approved	Angiotensinogen (AGT) increases the secretion of Hydrocortisone.	[47]
Nitric Oxide	DM1RBYG	Approved	Angiotensinogen (AGT) decreases the secretion of Nitric Oxide.	[48]
Aldosterone	DM9S2JW	Approved	Angiotensinogen (AGT) increases the abundance of Aldosterone.	[50]
AMG 386	DMQJXL4	Phase 3	Angiotensinogen (AGT) decreases the abundance of AMG 386.	[52]
(11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE	DMTPQ84	Investigative	Angiotensinogen (AGT) increases the secretion of (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE.	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Angiotensinogen (AGT).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Angiotensinogen (AGT).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Angiotensinogen (AGT).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Angiotensinogen (AGT).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Angiotensinogen (AGT).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Angiotensinogen (AGT).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Angiotensinogen (AGT).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Angiotensinogen (AGT).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Angiotensinogen (AGT).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Angiotensinogen (AGT).	[11]
Aspirin	DM672AH	Approved	Aspirin affects the activity of Angiotensinogen (AGT).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Angiotensinogen (AGT).	[13]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Angiotensinogen (AGT).	[14]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Angiotensinogen (AGT).	[15]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Angiotensinogen (AGT).	[16]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Angiotensinogen (AGT).	[17]
Propranolol	DM79NTF	Approved	Propranolol decreases the expression of Angiotensinogen (AGT).	[18]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the expression of Angiotensinogen (AGT).	[19]
Ketamine	DMT5HA4	Approved	Ketamine decreases the expression of Angiotensinogen (AGT).	[20]
Atenolol	DMNKG1Z	Approved	Atenolol decreases the expression of Angiotensinogen (AGT).	[21]
Spironolactone	DM2AQ5N	Approved	Spironolactone increases the expression of Angiotensinogen (AGT).	[22]
Furosemide	DMMQ8ZG	Approved	Furosemide increases the expression of Angiotensinogen (AGT).	[23]
Valsartan	DMREUQ6	Approved	Valsartan increases the expression of Angiotensinogen (AGT).	[24]
Amiloride	DMRTSGP	Approved	Amiloride increases the expression of Angiotensinogen (AGT).	[22]
Benazepril	DMH1M9B	Approved	Benazepril decreases the expression of Angiotensinogen (AGT).	[25]
Enalapril	DMNFUZR	Approved	Enalapril decreases the expression of Angiotensinogen (AGT).	[26]
Perindopril	DMOPZDT	Approved	Perindopril decreases the expression of Angiotensinogen (AGT).	[27]
Labetalol	DMK8U72	Approved	Labetalol decreases the expression of Angiotensinogen (AGT).	[18]
Rhucin	DM3ADGP	Approved	Rhucin increases the expression of Angiotensinogen (AGT).	[28]
Alprostadil	DMWH7NQ	Approved	Alprostadil increases the expression of Angiotensinogen (AGT).	[29]
Thiopental	DMGP8AX	Approved	Thiopental increases the expression of Angiotensinogen (AGT).	[20]
Reboxetine	DM26PRD	Approved	Reboxetine decreases the expression of Angiotensinogen (AGT).	[30]
Entresto	DMTWLXY	Phase 3	Entresto increases the expression of Angiotensinogen (AGT).	[32]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Angiotensinogen (AGT).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Angiotensinogen (AGT).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Angiotensinogen (AGT).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Angiotensinogen (AGT).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Angiotensinogen (AGT).	[38]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Angiotensinogen (AGT).	[39]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Angiotensinogen (AGT).	[40]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Angiotensinogen (AGT).	[41]
Uric acid	DMA1MKT	Investigative	Uric acid increases the expression of Angiotensinogen (AGT).	[43]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin decreases the activity of Angiotensinogen (AGT).	[44]
Irbesartan	DMTP1DC	Investigative	Irbesartan increases the expression of Angiotensinogen (AGT).	[24]
Lisinopril	DMUOK4C	Investigative	Lisinopril decreases the expression of Angiotensinogen (AGT).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the response to substance of Angiotensinogen (AGT).	[31]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Angiotensinogen (AGT).	[42]
4-oxo-nonenal	DMPX1J9	Investigative	4-oxo-nonenal affects the binding of Angiotensinogen (AGT).	[42]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
ORE-1001	DM471ZH	Phase 1/2	ORE-1001 affects the metabolism of Angiotensinogen (AGT).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Angiotensinogen (AGT).	[35]

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