Details of the Drug Combination

General Information of Drug Combination (ID: DCDMPHL)

Drug Combination Name
Lacosamide Nitrosoglutathione
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Lacosamide   DMVM6QR Nitrosoglutathione   DMZ9WI4
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 3.65
Bliss Independence Score: 3.65
Loewe Additivity Score: 14.9
LHighest Single Agent (HSA) Score: 14.9

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lacosamide
Disease Entry ICD 11 Status REF
Convulsion 8A68.Z Approved [2]
Epilepsy 8A60-8A68 Approved [3]
Diabetic neuropathy 8C0Z Phase 3 [2]
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 [3]
Voltage-gated sodium channel (Nav) TTIG65Q NOUNIPROTAC Inhibitor [3]
Dihydropyrimidinase related protein 2 (DPYSL2) TTZCW3T DPYL2_HUMAN Modulator [4]
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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 [5]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [6]
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Nitrosoglutathione Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
S-(hydroxymethyl)glutathione dehydrogenase (adh) DEAH3PE A0A0A7DS01_VIBCL Metabolism [7]
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Nitrosoglutathione Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine protease HTRA2, mitochondrial (HTRA2) OTC7616F HTRA2_HUMAN Affects Localization [8]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [9]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Increases Secretion [9]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Decreases Secretion [9]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [9]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Increases Activity [10]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [11]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Secretion [9]
Cystic fibrosis transmembrane conductance regulator (CFTR) OT6B22QH CFTR_HUMAN Decreases Expression [10]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [9]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Decreases Expression [9]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [8]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Activity [10]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [12]
Carbonyl reductase 1 (CBR1) OTQ3A541 CBR1_HUMAN Increases Reduction [13]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Response To Substance [14]
Alcohol dehydrogenase class-3 (ADH5) OTSO67MI ADHX_HUMAN Increases Reduction [15]
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⏷ Show the Full List of 19 DOT(s)

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: 7472).
3 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
4 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
5 Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4.
6 Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013 Dec;35(6):849-52.
7 Nitrosative stress response in Vibrio cholerae: role of S-nitrosoglutathione reductase. Appl Biochem Biotechnol. 2017 Jul;182(3):871-884.
8 The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells. Toxicol Appl Pharmacol. 2010 May 1;244(3):374-84. doi: 10.1016/j.taap.2010.02.004. Epub 2010 Feb 11.
9 Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. J Interferon Cytokine Res. 2003 Aug;23(8):423-31. doi: 10.1089/107999003322277838.
10 Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1. Biochem J. 2004 May 15;380(Pt 1):67-74. doi: 10.1042/BJ20031687.
11 Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors. Biochem Pharmacol. 1999 Jul 15;58(2):227-36. doi: 10.1016/s0006-2952(99)00097-0.
12 Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators nitric oxide and tumor necrosis factor-alpha in contrast to desferroxamine and phenylarsine oxide. J Biol Chem. 2001 Oct 26;276(43):39805-11. doi: 10.1074/jbc.M107689200. Epub 2001 Aug 20.
13 Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
14 Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor. Free Radic Biol Med. 1997;22(1-2):343-7. doi: 10.1016/s0891-5849(96)00336-x.
15 The Janus face of alcohol dehydrogenase 3. Chem Biol Interact. 2009 Mar 16;178(1-3):29-35. doi: 10.1016/j.cbi.2008.10.050. Epub 2008 Nov 6.