Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Angiotensin II receptor type-2 (AGTR2)
• Synonyms: Type-2 angiotensin II receptor; Angiotensin II type-2 receptor; Angiotensin II receptor 2; AT2
• Gene Name: AGTR2
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: AGTR2_HUMAN
• TTD ID: T09909
• Sequence:
  MKGNSTLATTSKNITSGLHFGLVNISGNNESTLNCSQKPSDKHLDAIPILYYIIFVIGFL
  VNIVVVTLFCCQKGPKKVSSIYIFNLAVADLLLLATLPLWATYYSYRYDWLFGPVMCKVF
  GSFLTLNMFASIFFITCMSVDRYQSVIYPFLSQRRNPWQASYIVPLVWCMACLSSLPTFY
  FRDVRTIEYLGVNACIMAFPPEKYAQWSAGIALMKNILGFIIPLIFIATCYFGIRKHLLK
  TNSYGKNRITRDQVLKMAAAVVLAFIICWLPFHVLTFLDALAWMGVINSCEVIAVIDLAL
  PFAILLGFTNSCVNPFLYCFVGNRFQQKLRSVFRVPITWLQGKRESMSCRKSSSLREMET
  FVS
• Function: Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation. Receptor for angiotensin II.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Renin-angiotensin system (hsa04614)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ANGIOTENSIN II	DMLWQ27	Increase blood pressure	BA04	Approved	[1]
SARALASIN	DMKS1DV	Hypertension	BA00-BA04	Approved	[2]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
EMA-401	DMYOUB6	Peripheral neuropathy	8C0Z	Phase 2	[3]
MP-157	DM5VXWO	Hypertension	BA00-BA04	Phase 1	[4]

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(biphenyl-4-yl-methyl)-1H-imidazole derivative 1	DMGYZQ2	N. A.	N. A.	Patented	[5]
Phenylpyridine derivative 3	DMDT5JI	N. A.	N. A.	Patented	[5]
PMID25416646-Compound-Figure5-E	DMYO7VH	N. A.	N. A.	Patented	[5]

9 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fonsartan	DM15LAP	Hypertension	BA00-BA04	Discontinued in Phase 2	[6]
L-158282	DMKSEIY	N. A.	N. A.	Discontinued in Phase 2	[7]
TAK-591	DM25DB4	Hypertension	BA00-BA04	Discontinued in Phase 1	[8]
L-158809	DMQ4LDB	Hypertension	BA00-BA04	Terminated	[7]
L-159689	DM9JE7Y	Hypertension	BA00-BA04	Terminated	[9]
L-162234	DMYSEBK	N. A.	N. A.	Terminated	[10]
PD-123319	DM92VUF	N. A.	N. A.	Terminated	[11]
SC-50560	DM8UDSF	N. A.	N. A.	Terminated	[12]
SC-51895	DMWO107	N. A.	N. A.	Terminated	[12]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
angiotensin III	DMYK0Z9	Discovery agent	N.A.	Investigative	[13]
L-159093	DMOX8JE	Discovery agent	N.A.	Investigative	[14]
L-162313	DMZOW96	Discovery agent	N.A.	Investigative	[15]
PD123177	DM4OQZX	Discovery agent	N.A.	Investigative	[16]
PMID22802221C21	DMVK1GT	Discovery agent	N.A.	Investigative	[17]
Sar-Arg-Val-Tyr-Ile-His-Pro-Ala	DMCNOJV	Discovery agent	N.A.	Investigative	[11]
Sar-Arg-Val-Tyr-Ile-His-Pro-Ile	DMS0FQC	Discovery agent	N.A.	Investigative	[11]
Sar-Arg-Val-Tyr-Ile-His-Pro-Phe-OH	DMD6SJT	Discovery agent	N.A.	Investigative	[18]
SC-52892	DMXA6LU	Discovery agent	N.A.	Investigative	[12]
SC-55634	DMLJ8T7	Discovery agent	N.A.	Investigative	[12]
[125I]CGP42112	DM1NXDA	Discovery agent	N.A.	Investigative	[19]

References

• [1] The preparation of (perfluoroalkyl)imidazoles as nonpeptide angiotensin II receptor antagonists, Bioorg. Med. Chem. Lett. 3(5):895-898 (1993).
• [2] cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8.
• [3] Clinical pipeline report, company report or official report of Spinifex.
• [4] As drug target reemerges, the question is to block or stimulate it. Nature Medicine. Spoonful of Medicine. 05 Feb 2014. Cassandra Willyard
• [5] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [6] Role of the angiotensin II AT2-subtype receptors in the blood pressure-lowering effect of losartan in salt-restricted rats. J Hypertens. 1998 Dec;16(12 Pt 2):2039-43.
• [7] Subtituted phenylthiophene benzoylsulfonamides with potent binding affinity to angiotensin II AT1 and AT2 receptors, Bioorg. Med. Chem. Lett. 4(1):189-194 (1994).
• [8] Clinical pipeline report, company report or official report of Takeda (2009).
• [9] The design, binding affinity prediction and synthesis of macrocyclic angiotensin II AT1 and AT2 receptor antagonists, Bioorg. Med. Chem. Lett. 6(8):923-928 (1996).
• [10] Quantized surface complementarity diversity (QSCD): a model based on small molecule-target complementarity. J Med Chem. 2000 May 18;43(10):1993-2006.
• [11] Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 sub... J Med Chem. 1991 Nov;34(11):3248-60.
• [12] N1-sterically hindered 2H-imidazol-2-one angiotensin II receptor antagonists: The conversion of surmountable antagonists to insurmountable antagonists, Bioorg. Med. Chem. Lett. 3(6):1055-1060 (1993).
• [13] URL: 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: 35).
• [14] A potent, orally active, balanced affinity angiotensin II AT1 antagonist and AT2 binding inhibitor. J Med Chem. 1993 Oct 15;36(21):3207-10.
• [15] Selective angiotensin II AT(2) receptor agonists with reduced CYP 450 inhibition. Bioorg Med Chem. 2010 Jun 15;18(12):4570-90.
• [16] Two distinct angiotensin II receptor binding sites in rat adrenal revealed by new selective nonpeptide ligands. Mol Pharmacol. 1990 Mar;37(3):347-51.
• [17] Compound 21 induces vasorelaxation via an endothelium- and angiotensin II type 2 receptor-independent mechanism. Hypertension. 2012 Sep;60(3):722-9.
• [18] 1-(carboxybenzyl)imidazole-5-acrylic acids: potent and selective angiotensin II receptor antagonists. J Med Chem. 1991 Apr;34(4):1514-7.
• [19] Radioiodinated CGP 42112A: a novel high affinity and highly selective ligand for the characterization of angiotensin AT2 receptors. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1365-71.