Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTP835K)

• DTT Name: ATP-binding cassette transporter C8 (ABCC8)
• Synonyms: Sulfonylurea receptor 1; SUR1-type K(ATP) channel; SUR1; Kir6.2/SUR1; ATPbinding cassette subfamily C member 8; ABCC8
• Gene Name: ABCC8
• DTT Type: Successful target; [1]
• BioChemical Class: ABC transporter
• UniProt ID: ABCC8_HUMAN
• TTD ID: T91480
• Sequence:
  MPLAFCGSENHSAAYRVDQGVLNNGCFVDALNVVPHVFLLFITFPILFIGWGSQSSKVHI
  HHSTWLHFPGHNLRWILTFMLLFVLVCEIAEGILSDGVTESHHLHLYMPAGMAFMAAVTS
  VVYYHNIETSNFPKLLIALLVYWTLAFITKTIKFVKFLDHAIGFSQLRFCLTGLLVILYG
  MLLLVEVNVIRVRRYIFFKTPREVKPPEDLQDLGVRFLQPFVNLLSKGTYWWMNAFIKTA
  HKKPIDLRAIGKLPIAMRALTNYQRLCEAFDAQVRKDIQGTQGARAIWQALSHAFGRRLV
  LSSTFRILADLLGFAGPLCIFGIVDHLGKENDVFQPKTQFLGVYFVSSQEFLANAYVLAV
  LLFLALLLQRTFLQASYYVAIETGINLRGAIQTKIYNKIMHLSTSNLSMGEMTAGQICNL
  VAIDTNQLMWFFFLCPNLWAMPVQIIVGVILLYYILGVSALIGAAVIILLAPVQYFVATK
  LSQAQRSTLEYSNERLKQTNEMLRGIKLLKLYAWENIFRTRVETTRRKEMTSLRAFAIYT
  SISIFMNTAIPIAAVLITFVGHVSFFKEADFSPSVAFASLSLFHILVTPLFLLSSVVRST
  VKALVSVQKLSEFLSSAEIREEQCAPHEPTPQGPASKYQAVPLRVVNRKRPAREDCRGLT
  GPLQSLVPSADGDADNCCVQIMGGYFTWTPDGIPTLSNITIRIPRGQLTMIVGQVGCGKS
  SLLLAALGEMQKVSGAVFWSSLPDSEIGEDPSPERETATDLDIRKRGPVAYASQKPWLLN
  ATVEENIIFESPFNKQRYKMVIEACSLQPDIDILPHGDQTQIGERGINLSGGQRQRISVA
  RALYQHANVVFLDDPFSALDIHLSDHLMQAGILELLRDDKRTVVLVTHKLQYLPHADWII
  AMKDGTIQREGTLKDFQRSECQLFEHWKTLMNRQDQELEKETVTERKATEPPQGLSRAMS
  SRDGLLQDEEEEEEEAAESEEDDNLSSMLHQRAEIPWRACAKYLSSAGILLLSLLVFSQL
  LKHMVLVAIDYWLAKWTDSALTLTPAARNCSLSQECTLDQTVYAMVFTVLCSLGIVLCLV
  TSVTVEWTGLKVAKRLHRSLLNRIILAPMRFFETTPLGSILNRFSSDCNTIDQHIPSTLE
  CLSRSTLLCVSALAVISYVTPVFLVALLPLAIVCYFIQKYFRVASRDLQQLDDTTQLPLL
  SHFAETVEGLTTIRAFRYEARFQQKLLEYTDSNNIASLFLTAANRWLEVRMEYIGACVVL
  IAAVTSISNSLHRELSAGLVGLGLTYALMVSNYLNWMVRNLADMELQLGAVKRIHGLLKT
  EAESYEGLLAPSLIPKNWPDQGKIQIQNLSVRYDSSLKPVLKHVNALIAPGQKIGICGRT
  GSGKSSFSLAFFRMVDTFEGHIIIDGIDIAKLPLHTLRSRLSIILQDPVLFSGTIRFNLD
  PERKCSDSTLWEALEIAQLKLVVKALPGGLDAIITEGGENFSQGQRQLFCLARAFVRKTS
  IFIMDEATASIDMATENILQKVVMTAFADRTVVTIAHRVHTILSADLVIVLKRGAILEFD
  KPEKLLSRKDSVFASFVRADK
• Function: Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Insulin secretion (hsa04911)
  Type II diabetes mellitus (hsa04930)
• Reactome Pathway:
  Regulation of insulin secretion (R-HSA-422356)
  ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DTT

6 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetohexamide	DMR6N7H	Diabetic complication	5A2Y	Approved	[2]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[3]
Gliclazide	DMN6QO5	Diabetic complication	5A2Y	Approved	[4]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[1]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[5]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[6]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NN-414	DMRJEXM	Type-1 diabetes	5A10	Phase 1	[7]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HBR-985	DMKDBFL	Discovery agent	N.A.	Investigative	[8]
NS-11757	DM98VMZ	Atrial fibrillation	BC81.3	Investigative	[9]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sulfonylurea receptor 1 (ABCC8) DTP Info
• Gene Name: ABCC8

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	[10]

References

• [1] Mechanism of disopyramide-induced hypoglycaemia in a patient with Type 2 diabetes. Diabet Med. 2009 Jan;26(1):76-8.
• [2] Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.Diabetes.2005 Nov;54(11):3065-72.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9.
• [5] Metformin/Repaglinide (PrandiMet) for type 2 diabetes. Med Lett Drugs Ther. 2009 Jun 1;51(1313):41-3.
• [6] 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.
• [7] Attenuation of hyperinsulinemia by NN414, a SUR1/Kir6.2 selective K-adenosine triphosphate channel opener, improves glucose tolerance and lipid profile in obese Zucker rats.Metabolism.2004 Apr;53(4):441-7.
• [8] Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem. 2001 Mar 29;44(7):1085-98.
• [9] 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. (Ligand id: 2944).
• [10] ABCC8 and ABCC9: ABC transporters that regulate K+ channels. Pflugers Arch. 2007 Feb;453(5):703-18.