Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTW5UDX)

• DTT Name: Urotensin II receptor (UTS2R)
• Synonyms: Urotensin-II receptor GPR14; UTS2R; UR-II-R; G protein coupled receptor 14
• Gene Name: UTS2R
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: UR2R_HUMAN
• TTD ID: T49072
• Sequence:
  MALTPESPSSFPGLAATGSSVPEPPGGPNATLNSSWASPTEPSSLEDLVATGTIGTLLSA
  MGVVGVVGNAYTLVVTCRSLRAVASMYVYVVNLALADLLYLLSIPFIVATYVTKEWHFGD
  VGCRVLFGLDFLTMHASIFTLTVMSSERYAAVLRPLDTVQRPKGYRKLLALGTWLLALLL
  TLPVMLAMRLVRRGPKSLCLPAWGPRAHRAYLTLLFATSIAGPGLLIGLLYARLARAYRR
  SQRASFKRARRPGARALRLVLGIVLLFWACFLPFWLWQLLAQYHQAPLAPRTARIVNYLT
  TCLTYGNSCANPFLYTLLTRNYRDHLRGRVRGPGSGGGRGPVPSLQPRARFQRCSGRSLS
  SCSPQPTDSLVLAPAAPARPAPEGPRAPA
• Function: High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK1440115	DMEJMTR	Asthma	CA23	Phase 1	[2]
SB-436811	DMLPB0X	Asthma	CA23	Phase 1	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PALOSURAN	DMWCLZ6	Renal failure	GB60-GB6Z	Discontinued in Phase 2	[1]
SAR101099	DMIZ7Q4	Diabetic nephropathy	GB61.Z	Discontinued in Phase 1	[3]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AC-7954	DM367MF	Discovery agent	N.A.	Investigative	[4]
Ac-FWKY-NH2	DM3XHIY	Discovery agent	N.A.	Investigative	[1]
Ac-SFWKYS-NH2	DM8XBR1	Discovery agent	N.A.	Investigative	[1]
Ac-WKY-NH2	DM7J9O6	Discovery agent	N.A.	Investigative	[1]
Ac-[CFWKFC]-NH2	DM9IN4T	Discovery agent	N.A.	Investigative	[1]
Ac-[CFWkYC]-NH2	DMW24UH	Discovery agent	N.A.	Investigative	[1]
AGTAD[CFWKYC]V	DMMO9YR	Discovery agent	N.A.	Investigative	[1]
FL104	DMO7U62	Discovery agent	N.A.	Investigative	[5]
ICI-199441	DMEWZ80	Discovery agent	N.A.	Investigative	[6]
JNJ-28318706	DM84PWI	Discovery agent	N.A.	Investigative	[7]
S6716	DMML1HC	Discovery agent	N.A.	Investigative	[8]
SB-328872	DMT1KFL	Discovery agent	N.A.	Investigative	[9]
SB-611812	DMASQV4	Discovery agent	N.A.	Investigative	[10]
SB-706375	DM9ZYNJ	Discovery agent	N.A.	Investigative	[1]
urotensin II-related peptide	DMCE3PJ	Discovery agent	N.A.	Investigative	[11]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	2.85E-02	-0.25	-0.57

References

• [1] Urotensin-II receptor modulators as potential drugs. J Med Chem. 2010 Apr 8;53(7):2695-708.
• [2] Effects of Urotensin II Receptor Antagonist, GSK1440115, in Asthma. Front Pharmacol. 2013; 4: 54.
• [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. (Target id: 365).
• [4] Isochromanone-based urotensin-II receptor agonists. Bioorg Med Chem. 2005 Apr 15;13(8):3057-68.
• [5] Novel and potent small-molecule urotensin II receptor agonists. Bioorg Med Chem. 2009 Jul 1;17(13):4657-65.
• [6] Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3716-9.
• [7] Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits. J Med Chem. 2009 Dec 10;52(23):7432-45.
• [8] Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Chem. 2002 Apr 25;45(9):1799-805.
• [9] Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides. Bioorg Med Chem Lett. 2008 Jul 15;18(14):3950-4.
• [10] A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J Mol Cell Cardiol. 2005 Nov;39(5):785-91.
• [11] Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain. Biochem Biophys Res Commun. 2003 Oct 24;310(3):860-8.