Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKRD0G)

• DTT Name: Endothelin A receptor (EDNRA)
• Synonyms: HET-AR; Endothelin-1 receptor; Endothelin receptor type A; Endothelin receptor A; ETRA; ETA-R; ETA receptor; ETA; ET-A
• Gene Name: EDNRA
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: EDNRA_HUMAN
• TTD ID: T23499
• Sequence:
  METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLP
  SNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIA
  SLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALS
  VDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCM
  LNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQ
  RREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATM
  NSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRS
  SHKDSMN
• Function: Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3. Receptor for endothelin-1.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
  Renin secretion (hsa04924)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[1]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[2]
LU302146	DMMJVXZ	Pulmonary hypertension	BB01	Approved	[3]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[4]
Sparsentan	DMMP51W	IgA nephropathy	MF8Y	Approved	[5]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[6]
Clazosentan	DMQSBX4	Cerebral vasospasm	BA85.Z	Phase 3	[7]
Darusentan	DMN8DQH	Hypotension	BA20-BA21	Phase 3	[8]
PF-1228305	DMS1EQ7	Pulmonary hypertension	BB01	Phase 3	[9]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[10]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[11]
PD-145065	DMWVBTQ	Hypertension	BA00-BA04	Phase 2	[12]
TBC-3711	DMZCA0K	Hypotension	BA20-BA21	Phase 2	[13]
YM-598	DMUPJWH	Prostate cancer	2C82.0	Phase 2	[14]
PMZ-2123	DMQ82SH	Cerebral oedema in diabetic ketoacidosis	8D60.1	Phase 1	[15]

21 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sitaxsentan	DMKM5HB	Pulmonary arterial hypertension	BB01.0	Withdrawn from market	[16]
TBC 11251 (TBC)	DMFR79T	Pulmonary arterial hypertension	BB01.0	Withdrawn from market	[17]
Zibotentan	DMIK6C9	Prostate cancer	2C82.0	Discontinued in Phase 3	[18]
97-139	DMG0I6L	Cerebrovascular disease	8B2Z	Discontinued in Phase 2	[19]
Avosentan	DM2I8NT	Diabetic nephropathy	GB61.Z	Discontinued in Phase 2	[20]
BMS-193884	DMODK2J	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[21]
EDONENTAN HYDRATE	DMRPUEC	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[22]
ENRASENTAN	DM05F1Z	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[23]
J-104132	DM5E6MK	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[24]
SB-209670	DMJYW80	Arrhythmia	BC9Z	Discontinued in Phase 2	[25]
A-216546	DMHT84I	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[26]
SB-234551	DMX7PNY	Nerve injury	ND56.4	Discontinued in Phase 1	[27]
ZD-1611	DMUDLFM	Hypotension	BA20-BA21	Discontinued in Phase 1	[28]
50-235	DMM3UK5	Hypertension	BA00-BA04	Terminated	[30]
BMS-182874	DM5PG6C	Hypertension	BA00-BA04	Terminated	[31]
BQ-518	DM3O4BG	Hypertension	BA00-BA04	Terminated	[32]
BQ610	DMPRNQL	N. A.	N. A.	Terminated	[33]
MX-6120	DMXW67H	Heart disease	BA41-BA42	Terminated	[34]
PD-155080	DMQCNWD	Hypertension	BA00-BA04	Terminated	[35]
PD142893	DMFA27N	N. A.	N. A.	Terminated	[33]
PD156707	DMAVZEJ	N. A.	N. A.	Terminated	[36]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ET-1	DMA85ND	N. A.	N. A.	Phase 0	[29]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-HYDROXY-3,5-DIIODOBENZOIC ACID	DMDOHRF	Discovery agent	N.A.	Investigative	[37]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[38]
Ac-bhg-F-N-Y-Y-W	DM1KDJV	Discovery agent	N.A.	Investigative	[39]
Ac-w-F-F-N-Y-Y-W	DMP89K4	Discovery agent	N.A.	Investigative	[39]
Asterric acid	DMJAPFH	Discovery agent	N.A.	Investigative	[40]
Bhg-F-N-Y-Y-W	DMVH4LK	Discovery agent	N.A.	Investigative	[39]
BMS-187308	DMJ218E	Discovery agent	N.A.	Investigative	[41]
Endothelin-2	DMOEIYQ	Discovery agent	N.A.	Investigative	[29]
HJP-272	DMWIOCY	Premature labour	JB00	Investigative	[42]
LU302872	DM7F3SE	Discovery agent	N.A.	Investigative	[3]
PD-163140	DMBZ09U	Discovery agent	N.A.	Investigative	[43]
PD164333	DM5421R	Discovery agent	N.A.	Investigative	[44]
sarafotoxin S6b	DMR6PJ5	Discovery agent	N.A.	Investigative	[45]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Ser-Val-Tyr-Phe-Cys)	DM48QTG	Discovery agent	N.A.	Investigative	[46]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Val-Tyr-Phe-Cys)	DMOZX8M	Discovery agent	N.A.	Investigative	[46]
W-F-F-N--Y-Y-W	DMAXOIS	Discovery agent	N.A.	Investigative	[39]
[125I]PD151242	DM4HLO5	Discovery agent	N.A.	Investigative	[47]
[3H]BQ123	DMG8T3W	Discovery agent	N.A.	Investigative	[48]
[3H]S0139	DM32IAB	Discovery agent	N.A.	Investigative	[42]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	3.19E-05	-2.69	-1.71
Preterm birth	KA21.4Z	Myometrium	5.13E-01	-0.82	-0.79

References

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