Details of the Drug Combination

General Information of Drug Combination (ID: DCQZIIO)

• Drug Combination Name: Acetohexamide + Lacosamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Acetohexamide (DMR6N7H): Small molecular drug
  Lacosamide (DMVM6QR): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 29.35
  Bliss Independence Score: 29.35
  Loewe Additivity Score: 41.61
  LHighest Single Agent (HSA) Score: 41.62

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Acetohexamide

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[2]

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	[5]

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	[6]
Short-chain dehydrogenase/reductase retSDR1 (DHRS3)	DEXPVUN	DHRS3_HUMAN	Metabolism	[7]

Acetohexamide Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[8]
Carbonyl reductase 3 (CBR3)	OT9G6SF0	CBR3_HUMAN	Increases ADR	[9]

Indication(s) of Lacosamide

Disease Entry	ICD 11	Status	REF
Convulsion	8A68.Z	Approved	[3]
Epilepsy	8A60-8A68	Approved	[4]
Diabetic neuropathy	8C0Z	Phase 3	[3]

Lacosamide Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A)	TTN9VTF	SCNBA_HUMAN	Inhibitor	[4]
Voltage-gated sodium channel (Nav)	TTIG65Q	NOUNIPROTAC	Inhibitor	[4]
Dihydropyrimidinase related protein 2 (DPYSL2)	TTZCW3T	DPYL2_HUMAN	Modulator	[10]

Lacosamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[11]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[12]

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] 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).
• [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: 7472).
• [4] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [5] Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.Diabetes.2005 Nov;54(11):3065-72.
• [6] Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83.
• [7] Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). Chem Biol Interact. 2015 Jun 5;234:178-87.
• [8] 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.
• [9] 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.
• [10] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [11] Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4.
• [12] Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013 Dec;35(6):849-52.