Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEF5MJ)

• DTT Name: ATP-binding cassette transporter C9 (ABCC9)
• Synonyms: Sulfonylurea receptor 2; SUR2; ATP-binding cassette sub-family C member 9
• Gene Name: ABCC9
• DTT Type: Successful target; [1]
• BioChemical Class: ABC transporter
• UniProt ID: ABCC9_HUMAN
• TTD ID: T02777
• Sequence:
  MSLSFCGNNISSYNINDGVLQNSCFVDALNLVPHVFLLFITFPILFIGWGSQSSKVQIHH
  NTWLHFPGHNLRWILTFALLFVHVCEIAEGIVSDSRRESRHLHLFMPAVMGFVATTTSIV
  YYHNIETSNFPKLLLALFLYWVMAFITKTIKLVKYCQSGLDISNLRFCITGMMVILNGLL
  MAVEINVIRVRRYVFFMNPQKVKPPEDLQDLGVRFLQPFVNLLSKATYWWMNTLIISAHK
  KPIDLKAIGKLPIAMRAVTNYVCLKDAYEEQKKKVADHPNRTPSIWLAMYRAFGRPILLS
  STFRYLADLLGFAGPLCISGIVQRVNETQNGTNNTTGISETLSSKEFLENAYVLAVLLFL
  ALILQRTFLQASYYVTIETGINLRGALLAMIYNKILRLSTSNLSMGEMTLGQINNLVAIE
  TNQLMWFLFLCPNLWAMPVQIIMGVILLYNLLGSSALVGAAVIVLLAPIQYFIATKLAEA
  QKSTLDYSTERLKKTNEILKGIKLLKLYAWEHIFCKSVEETRMKELSSLKTFALYTSLSI
  FMNAAIPIAAVLATFVTHAYASGNNLKPAEAFASLSLFHILVTPLFLLSTVVRFAVKAII
  SVQKLNEFLLSDEIGDDSWRTGESSLPFESCKKHTGVQPKTINRKQPGRYHLDSYEQSTR
  RLRPAETEDIAIKVTNGYFSWGSGLATLSNIDIRIPTGQLTMIVGQVGCGKSSLLLAILG
  EMQTLEGKVHWSNVNESEPSFEATRSRNRYSVAYAAQKPWLLNATVEENITFGSPFNKQR
  YKAVTDACSLQPDIDLLPFGDQTEIGERGINLSGGQRQRICVARALYQNTNIVFLDDPFS
  ALDIHLSDHLMQEGILKFLQDDKRTLVLVTHKLQYLTHADWIIAMKDGSVLREGTLKDIQ
  TKDVELYEHWKTLMNRQDQELEKDMEADQTTLERKTLRRAMYSREAKAQMEDEDEEEEEE
  EDEDDNMSTVMRLRTKMPWKTCWRYLTSGGFFLLILMIFSKLLKHSVIVAIDYWLATWTS
  EYSINNTGKADQTYYVAGFSILCGAGIFLCLVTSLTVEWMGLTAAKNLHHNLLNKIILGP
  IRFFDTTPLGLILNRFSADTNIIDQHIPPTLESLTRSTLLCLSAIGMISYATPVFLVALL
  PLGVAFYFIQKYFRVASKDLQELDDSTQLPLLCHFSETAEGLTTIRAFRHETRFKQRMLE
  LTDTNNIAYLFLSAANRWLEVRTDYLGACIVLTASIASISGSSNSGLVGLGLLYALTITN
  YLNWVVRNLADLEVQMGAVKKVNSFLTMESENYEGTMDPSQVPEHWPQEGEIKIHDLCVR
  YENNLKPVLKHVKAYIKPGQKVGICGRTGSGKSSLSLAFFRMVDIFDGKIVIDGIDISKL
  PLHTLRSRLSIILQDPILFSGSIRFNLDPECKCTDDRLWEALEIAQLKNMVKSLPGGLDA
  VVTEGGENFSVGQRQLFCLARAFVRKSSILIMDEATASIDMATENILQKVVMTAFADRTV
  VTIAHRVSSIMDAGLVLVFSEGILVECDTVPNLLAHKNGLFSTLVMTNK
• Function: Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.
• KEGG Pathway: ABC transporters (hsa02010)
• Reactome Pathway:
  ABC-family proteins mediated transport (R-HSA-382556)
  Ion homeostasis (R-HSA-5578775)
  Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome (R-HSA-5678420)
  ATP sensitive Potassium channels (R-HSA-1296025)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[1]
Nicorandil	DMIYJFV	Angina pectoris	BA40	Approved	[2]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[3]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[4]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BTS-67582	DM54K2P	Diabetic complication	5A2Y	Discontinued in Phase 2	[5]
KRN-2391	DMZ1SEW	Angina pectoris	BA40	Discontinued in Phase 2	[6]
BMS-191095	DMKFXTD	Angina pectoris	BA40	Discontinued in Phase 1	[7]
CCX915	DMHMST3	Multiple sclerosis	8A40	Discontinued in Phase 1	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	6.51E-01	0.02	0.06
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	8.46E-01	0.02	0.22

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sulfonylurea receptor 2 (ABCC9) DTP Info
• Gene Name: ABCC9

1 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[9]

References

• [1] Mechanism of disopyramide-induced hypoglycaemia in a patient with Type 2 diabetes. Diabet Med. 2009 Jan;26(1):76-8.
• [2] A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the physiology and pharmacology of cardiovascular ATP-sensitive K(+) chann... J Mol Cell Cardiol. 2005 Jul;39(1):1-6.
• [3] Metformin/Repaglinide (PrandiMet) for type 2 diabetes. Med Lett Drugs Ther. 2009 Jun 1;51(1313):41-3.
• [4] Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes. J Clin Invest. 2009 Jan;119(1):80-90.
• [5] BTS-67582 (Knoll Pharmaceuticals Co). IDrugs. 1999 Apr;2(4):355-9.
• [6] Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes
• [7] The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats.J Cereb Blood Flow Metab.2007 Feb;27(2):348-55.
• [8] Analysis of the differential modulation of sulphonylurea block of beta-cell and cardiac ATP-sensitive K+ (K(ATP)) channels by Mg-nucleotides. J Physiol. 2003 Feb 15;547(Pt 1):159-68.
• [9] ABCC8 and ABCC9: ABC transporters that regulate K+ channels. Pflugers Arch. 2007 Feb;453(5):703-18.