Details of the Drug Combination

General Information of Drug Combination (ID: DCO73WU)

• Drug Combination Name: Miglustat + Acetohexamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Miglustat (DM5J64S): Small molecular drug
  Acetohexamide (DMR6N7H): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.94
  Bliss Independence Score: 11.94
  Loewe Additivity Score: 22.44
  LHighest Single Agent (HSA) Score: 22.47

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Miglustat

Disease Entry	ICD 11	Status	REF
Niemann-Pick disease type C	N.A.	Approved	[2]
Type 1 gaucher disease	5C56.0Y	Approved	[3]
Gaucher disease	5C56.0Y	Investigative	[2]

Miglustat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ceramide glucosyltransferase (UGCG)	TTPHEX3	CEGT_HUMAN	Inhibitor	[5]

Miglustat Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Increases Activity	[6]

Indication(s) of Acetohexamide

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[4]

Acetohexamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette transporter C8 (ABCC8)	TTP835K	ABCC8_HUMAN	Modulator	[7]

Acetohexamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Short-chain dehydrogenase/reductase retSDR1 (DHRS3)	DEXPVUN	DHRS3_HUMAN	Metabolism	[9]

Acetohexamide Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[10]
Carbonyl reductase 3 (CBR3)	OT9G6SF0	CBR3_HUMAN	Increases ADR	[11]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Miglustat FDA Label
• [3] 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: 4841).
• [4] 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: 6793).
• [5] Effect of miglustat on bone disease in adults with type 1 Gaucher disease: a pooled analysis of three multinational, open-label studies. Clin Ther. 2007 Aug;29(8):1645-54.
• [6] Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622. J Pharmacol Exp Ther. 2008 Apr;325(1):89-99. doi: 10.1124/jpet.107.134502. Epub 2008 Jan 29.
• [7] Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.Diabetes.2005 Nov;54(11):3065-72.
• [8] Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83.
• [9] Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). Chem Biol Interact. 2015 Jun 5;234:178-87.
• [10] Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1590-8. doi: 10.1016/j.jchromb.2010.04.019.
• [11] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.