Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T09909
(Former ID: TTDS00525)
|
|||||
| Target Name |
Angiotensin II receptor type-2 (AGTR2)
|
|||||
| Synonyms |
Type-2 angiotensin II receptor; Angiotensin II type-2 receptor; Angiotensin II receptor 2; AT2
Click to Show/Hide
|
|||||
| Gene Name |
AGTR2
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Hypertension [ICD-11: BA00-BA04] | |||||
| 2 | Secondary hypertension [ICD-11: BA04] | |||||
| Function |
Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation. Receptor for angiotensin II.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR rhodopsin
|
|||||
| UniProt ID | ||||||
| Sequence |
MKGNSTLATTSKNITSGLHFGLVNISGNNESTLNCSQKPSDKHLDAIPILYYIIFVIGFL
VNIVVVTLFCCQKGPKKVSSIYIFNLAVADLLLLATLPLWATYYSYRYDWLFGPVMCKVF GSFLTLNMFASIFFITCMSVDRYQSVIYPFLSQRRNPWQASYIVPLVWCMACLSSLPTFY FRDVRTIEYLGVNACIMAFPPEKYAQWSAGIALMKNILGFIIPLIFIATCYFGIRKHLLK TNSYGKNRITRDQVLKMAAAVVLAFIICWLPFHVLTFLDALAWMGVINSCEVIAVIDLAL PFAILLGFTNSCVNPFLYCFVGNRFQQKLRSVFRVPITWLQGKRESMSCRKSSSLREMET FVS Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T32W5X ; T43NBB | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | ANGIOTENSIN II | Drug Info | Approved | Increase blood pressure | [2] | |
| 2 | SARALASIN | Drug Info | Approved | Hypertension | [3], [4] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | EMA-401 | Drug Info | Phase 2 | Postherpetic neuralgia | [5], [6] | |
| 2 | MP-157 | Drug Info | Phase 1 | Hypertension | [7] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | Fonsartan | Drug Info | Discontinued in Phase 2 | Hypertension | [8] | |
| 2 | TAK-591 | Drug Info | Discontinued in Phase 1 | Hypertension | [9] | |
| 3 | L-158809 | Drug Info | Terminated | Hypertension | [10] | |
| 4 | L-159689 | Drug Info | Terminated | Hypertension | [11] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 16 Inhibitor drugs | + | ||||
| 1 | ANGIOTENSIN II | Drug Info | [1] | |||
| 2 | SARALASIN | Drug Info | [12] | |||
| 3 | L-158282 | Drug Info | [17] | |||
| 4 | L-158809 | Drug Info | [17] | |||
| 5 | L-159689 | Drug Info | [19] | |||
| 6 | L-162234 | Drug Info | [20] | |||
| 7 | PD-123319 | Drug Info | [21] | |||
| 8 | SC-50560 | Drug Info | [22] | |||
| 9 | SC-51895 | Drug Info | [22] | |||
| 10 | L-159093 | Drug Info | [24] | |||
| 11 | L-162313 | Drug Info | [25] | |||
| 12 | Sar-Arg-Val-Tyr-Ile-His-Pro-Ala | Drug Info | [21] | |||
| 13 | Sar-Arg-Val-Tyr-Ile-His-Pro-Ile | Drug Info | [21] | |||
| 14 | Sar-Arg-Val-Tyr-Ile-His-Pro-Phe-OH | Drug Info | [28] | |||
| 15 | SC-52892 | Drug Info | [22] | |||
| 16 | SC-55634 | Drug Info | [22] | |||
| Antagonist | [+] 3 Antagonist drugs | + | ||||
| 1 | EMA-401 | Drug Info | [13] | |||
| 2 | TAK-591 | Drug Info | [18] | |||
| 3 | PD123177 | Drug Info | [26] | |||
| Agonist | [+] 7 Agonist drugs | + | ||||
| 1 | MP-157 | Drug Info | [14] | |||
| 2 | 1-(biphenyl-4-yl-methyl)-1H-imidazole derivative 1 | Drug Info | [15] | |||
| 3 | Phenylpyridine derivative 3 | Drug Info | [15] | |||
| 4 | PMID25416646-Compound-Figure5-E | Drug Info | [15] | |||
| 5 | angiotensin III | Drug Info | [23] | |||
| 6 | PMID22802221C21 | Drug Info | [27] | |||
| 7 | [125I]CGP42112 | Drug Info | [29], [30] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Fonsartan | Drug Info | [16] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Adrenergic signaling in cardiomyocytes | hsa04261 | Affiliated Target |
|
| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Renin-angiotensin system | hsa04614 | Affiliated Target |
|
| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.87E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.50E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Adrenergic signaling in cardiomyocytes | |||||
| 3 | Renin-angiotensin system | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | ACE Inhibitor Pathway | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Peptide GPCRs | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | The preparation of (perfluoroalkyl)imidazoles as nonpeptide angiotensin II receptor antagonists, Bioorg. Med. Chem. Lett. 3(5):895-898 (1993). | |||||
| REF 2 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 3 | 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. (Ligand id: 598). | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | 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. (Ligand id: 8374). | |||||
| REF 6 | ClinicalTrials.gov (NCT02435199) Clinical Trial Designed to Determine the Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy. U.S. National Institutes of Health. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034178) | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005209) | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028308) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001562) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003495) | |||||
| REF 12 | 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. | |||||
| REF 13 | Clinical pipeline report, company report or official report of Spinifex. | |||||
| REF 14 | As drug target reemerges, the question is to block or stimulate it. Nature Medicine. Spoonful of Medicine. 05 Feb 2014. Cassandra Willyard | |||||
| REF 15 | PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91. | |||||
| REF 16 | 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. | |||||
| REF 17 | Subtituted phenylthiophene benzoylsulfonamides with potent binding affinity to angiotensin II AT1 and AT2 receptors, Bioorg. Med. Chem. Lett. 4(1):189-194 (1994). | |||||
| REF 18 | Clinical pipeline report, company report or official report of Takeda (2009). | |||||
| REF 19 | 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). | |||||
| REF 20 | Quantized surface complementarity diversity (QSCD): a model based on small molecule-target complementarity. J Med Chem. 2000 May 18;43(10):1993-2006. | |||||
| REF 21 | 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. | |||||
| REF 22 | 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). | |||||
| REF 23 | 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). | |||||
| REF 24 | A potent, orally active, balanced affinity angiotensin II AT1 antagonist and AT2 binding inhibitor. J Med Chem. 1993 Oct 15;36(21):3207-10. | |||||
| REF 25 | Selective angiotensin II AT(2) receptor agonists with reduced CYP 450 inhibition. Bioorg Med Chem. 2010 Jun 15;18(12):4570-90. | |||||
| REF 26 | Two distinct angiotensin II receptor binding sites in rat adrenal revealed by new selective nonpeptide ligands. Mol Pharmacol. 1990 Mar;37(3):347-51. | |||||
| REF 27 | Compound 21 induces vasorelaxation via an endothelium- and angiotensin II type 2 receptor-independent mechanism. Hypertension. 2012 Sep;60(3):722-9. | |||||
| REF 28 | 1-(carboxybenzyl)imidazole-5-acrylic acids: potent and selective angiotensin II receptor antagonists. J Med Chem. 1991 Apr;34(4):1514-7. | |||||
| REF 29 | 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. | |||||
| REF 30 | Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin Sci (Lond). 2011 Oct;121(7):297-303. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.