Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2THBD)

• DTT Name: P2X purinoceptor 3 (P2RX3)
• Synonyms: P2X3 receptor; P2X3; P2RX3; ATP-gated ion channel P2X(3)
• Gene Name: P2RX3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: ATP-gated P2X receptor cation channel
• UniProt ID: P2RX3_HUMAN
• TTD ID: T17140
• Sequence:
  MNCISDFFTYETTKSVVVKSWTIGIINRVVQLLIISYFVGWVFLHEKAYQVRDTAIESSV
  VTKVKGSGLYANRVMDVSDYVTPPQGTSVFVIITKMIVTENQMQGFCPESEEKYRCVSDS
  QCGPERLPGGGILTGRCVNYSSVLRTCEIQGWCPTEVDTVETPIMMEAENFTIFIKNSIR
  FPLFNFEKGNLLPNLTARDMKTCRFHPDKDPFCPILRVGDVVKFAGQDFAKLARTGGVLG
  IKIGWVCDLDKAWDQCIPKYSFTRLDSVSEKSSVSPGYNFRFAKYYKMENGSEYRTLLKA
  FGIRFDVLVYGNAGKFNIIPTIISSVAAFTSVGVGTVLCDIILLNFLKGADQYKAKKFEE
  VNETTLKIAALTNPVYPSDQTTAEKQSTDSGAFSIGH
• Function: Receptor for ATP that acts as a ligand-gated ionchannel.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  Platelet homeostasis (R-HSA-418346)
  Elevation of cytosolic Ca2+ levels (R-HSA-139853)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gefapixant	DM4GWL7	Cough	MD12	Phase 3	[1]
BAY-1902607	DMYSQMW	Cough	MD12	Phase 2	[1]
BAY 1902607	DMFA4CK	Cough	MD12	Phase 1/2	[1]
AF-130	DM8LG2I	Hypertension	BA00-BA04	Phase 1	[2]
BAY 1817080	DMF9ALP	Cough	MD12	Phase 1	[3]
BAY-1817080	DMNL5G7	Endometriosis	GA10	Phase 1	[1]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AF353	DMXQ3MO	Discovery agent	N.A.	Investigative	[4]
AVVYPWT	DMK9BMQ	Discovery agent	N.A.	Investigative	[5]
BzATP	DM37GYA	Discovery agent	N.A.	Investigative	[6]
Cyclic LVVYPWT	DM2JE5F	Discovery agent	N.A.	Investigative	[5]
ISOPPADS	DMWI0M8	Discovery agent	N.A.	Investigative	[7]
LAVYPWT	DMOK6IP	Discovery agent	N.A.	Investigative	[5]
LVAYPWT	DMIO405	Discovery agent	N.A.	Investigative	[5]
LVVAPWT	DM78Z9D	Discovery agent	N.A.	Investigative	[5]
LVVYPWT	DM1QPG7	Discovery agent	N.A.	Investigative	[5]
MK-3901	DM5EQ7F	Pain	MG30-MG3Z	Investigative	[6]
RO3	DMRYNJE	Discovery agent	N.A.	Investigative	[8]
TNP-ATP	DMVZY0X	Discovery agent	N.A.	Investigative	[9]
[3H]A317491	DMTBAXD	Discovery agent	N.A.	Investigative	[10]

References

• [1] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study. Eur Respir J. 2021 May 13;2004240.
• [4] AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol. 2010 Jul;160(6):1387-98.
• [5] Structure-activity relationship studies of spinorphin as a potent and selective human P2X(3) receptor antagonist. J Med Chem. 2007 Sep 6;50(18):4543-7.
• [6] 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: 480).
• [7] Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X1 receptors. J Med Chem. 2001 Feb 1;44(3):340-9.
• [8] Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol. 2006 Feb;147 Suppl 2:S132-43.
• [9] Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3, and heteromeric P2X2/3 receptors. Mol Pharmacol. 1998 Jun;53(6):969-73.
• [10] Crossing the pain barrier: P2 receptors as targets for novel analgesics. J Physiol. 2003 Dec 15;553(Pt 3):683-94.