Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG140O)

• DTT Name: Inward rectifier potassium channel Kir1.2 (KCNJ10)
• Synonyms: Potassiumchannel, inwardly rectifying, subfamily J, member 10; Potassium channel, inwardly rectifying subfamily J member 10; Inward rectifier K+ channel Kir1.2; Inward rectifier K(+) channel Kir1.2; ATP-sensitive inward rectifier potassium channel 10; ATP-dependent inwardly rectifying potassium channel Kir4.1; ATP dependent K+ channel
• Gene Name: KCNJ10
• DTT Type: Successful target; [1]
• BioChemical Class: Inward rectifier potassium channel
• UniProt ID: KCJ10_HUMAN
• TTD ID: T09423
• Sequence:
  MTSVAKVYYSQTTQTESRPLMGPGIRRRRVLTKDGRSNVRMEHIADKRFLYLKDLWTTFI
  DMQWRYKLLLFSATFAGTWFLFGVVWYLVAVAHGDLLELDPPANHTPCVVQVHTLTGAFL
  FSLESQTTIGYGFRYISEECPLAIVLLIAQLVLTTILEIFITGTFLAKIARPKKRAETIR
  FSQHAVVASHNGKPCLMIRVANMRKSLLIGCQVTGKLLQTHQTKEGENIRLNQVNVTFQV
  DTASDSPFLILPLTFYHVVDETSPLKDLPLRSGEGDFELVLILSGTVESTSATCQVRTSY
  LPEEILWGYEFTPAISLSASGKYIADFSLFDQVVKVASPSGLRDSTVRYGDPEKLKLEES
  LREQAEKEGSALSVRISNV
• Function: Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium. In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules. May be responsible for potassium buffering action of glial cells in the brain.
• KEGG Pathway: Gastric acid secretion (hsa04971)
• Reactome Pathway:
  Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits (R-HSA-997272)
  Activation of G protein gated Potassium channels (R-HSA-1296041)

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Chlorpropamide	DMPHZQE	Non-insulin dependent diabetes	5A11	Approved	[2]
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[3]
Gliquidone	DMB0EUX	Diabetic complication	5A2Y	Approved	[4]
Glisoxepide	DMJPR2B	Non-insulin dependent diabetes	5A11	Approved	[5]
Glycodiazine	DM1WL9O	Diabetic complication	5A2Y	Approved	[6]
Mitiglinide	DMP8HEL	Diabetic complication	5A2Y	Approved	[1]
Tolazamide	DMIHRNA	Diabetic complication	5A2Y	Approved	[7]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulfonylthioureas	DMBG0H1	Discovery agent	N.A.	Investigative	[8]

References

• [1] Carboxyl-glucuronidation of mitiglinide by human UDP-glucuronosyltransferases. Biochem Pharmacol. 2007 Jun 1;73(11):1842-51.
• [2] Effect of the chlorpropamide and fructose-1,6-bisphosphate of soluble TNF receptor II levels. Pharmacol Res. 2004 May;49(5):449-53.
• [3] Triggering and amplification of insulin secretion by dimethyl alpha-ketoglutarate, a membrane permeable alpha-ketoglutarate analogue. Eur J Pharmacol. 2009 Apr 1;607(1-3):41-6.
• [4] Hydroxyl-substituted sulfonylureas as potent inhibitors of specific [3H]glyburide binding to rat brain synaptosomes. Bioorg Med Chem. 2003 May 1;11(9):2099-113.
• [5] Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J Pharmacol Exp Ther. 2006 Jan;316(1):182-8.
• [6] Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions. Pflugers Arch. 1977 Apr 25;368(3):245-52.
• [7] Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock. Shock. 1996 Jun;5(6):391-4.
• [8] Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem. 2001 Mar 29;44(7):1085-98.