Details of the Drug Combination

General Information of Drug Combination (ID: DCO6CTL)

Drug Combination Name
Sertraline Miglustat
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Sertraline   DM0FB1J Miglustat   DM5J64S
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 7.84
Bliss Independence Score: 7.84
Loewe Additivity Score: 21.33
LHighest Single Agent (HSA) Score: 21.34

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sertraline
Disease Entry ICD 11 Status REF
Coronary heart disease BA80.Z Approved [2]
Depression 6A70-6A7Z Approved [3]
Epilepsy 8A60-8A68 Approved [2]
Obsessive compulsive disorder 6B20 Approved [2]
Panic disorder 6B01 Approved [2]
Post-traumatic stress disorder 6B40 Approved [2]
Sertraline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [10]
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Sertraline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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Sertraline Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [17]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
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⏷ Show the Full List of 7 DME(s)
Sertraline Interacts with 88 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [18]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [19]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [21]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Increases Expression [6]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [6]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [6]
Serine protease hepsin (HPN) OT7QNA61 HEPS_HUMAN Increases Expression [6]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [6]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [6]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [6]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Increases Expression [6]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [6]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [6]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [6]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [6]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [6]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [6]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [6]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [22]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Expression [22]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [23]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13) OTS93BTX M3K13_HUMAN Increases Expression [7]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [7]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [7]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 14 (DUSP14) OTGODFCR DUS14_HUMAN Increases Expression [7]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) OTBMJUOC M4K4_HUMAN Decreases Expression [7]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [7]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [24]
Alpha-crystallin A chain (CRYAA) OTSN7JUR CRYAA_HUMAN Increases Expression [7]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [25]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [26]
Platelet factor 4 (PF4) OTEMJU68 PLF4_HUMAN Decreases Expression [8]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [7]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [7]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Increases Expression [27]
Monocyte differentiation antigen CD14 (CD14) OT83GJ47 CD14_HUMAN Decreases Expression [7]
Heat shock 70 kDa protein 1A (HSPA1A) OTKGIE76 HS71A_HUMAN Increases Expression [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [24]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [7]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2) OTNIZPEA ATF2_HUMAN Increases Expression [7]
P-selectin (SELP) OTWR90PK LYAM3_HUMAN Decreases Expression [26]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [8]
E-selectin (SELE) OT33RZWY LYAM2_HUMAN Decreases Expression [26]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Decreases Expression [7]
Heat shock 70 kDa protein 6 (HSPA6) OTH4S7WB HSP76_HUMAN Increases Expression [7]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [7]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [7]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [9]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [24]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [24]
Dual specificity protein phosphatase 1 (DUSP1) OTN6BR75 DUS1_HUMAN Increases Expression [7]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [7]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) OTOZTA1F M3K8_HUMAN Increases Expression [7]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Translocon-associated protein subunit beta (SSR2) OTQJSL7M SSRB_HUMAN Increases Expression [7]
Caspase-4 (CASP4) OTVQTV1L CASP4_HUMAN Increases Cleavage [7]
Ribosomal protein S6 kinase alpha-3 (RPS6KA3) OTYJNNMD KS6A3_HUMAN Decreases Expression [7]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [7]
Protein transport protein Sec61 subunit gamma (SEC61G) OT7MJRXY SC61G_HUMAN Decreases Expression [7]
E3 ubiquitin-protein ligase RBX1 (RBX1) OTYA1UIO RBX1_HUMAN Decreases Expression [7]
S-phase kinase-associated protein 1 (SKP1) OT5BPAZ4 SKP1_HUMAN Decreases Expression [7]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [7]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [7]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [28]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [9]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [7]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [9]
Cullin-1 (CUL1) OTXPE1UZ CUL1_HUMAN Decreases Expression [7]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [7]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Phosphorylation [9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [7]
E3 ubiquitin-protein ligase synoviolin (SYVN1) OTZ4ZJP5 SYVN1_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 16 (DUSP16) OTK7S078 DUS16_HUMAN Increases Expression [7]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [9]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [29]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [7]
Serine/threonine-protein kinase TAO2 (TAOK2) OTNUMOZ1 TAOK2_HUMAN Increases Expression [7]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3) OT0X8ACY JIP3_HUMAN Increases Expression [7]
Dual specificity protein phosphatase 10 (DUSP10) OTNG467B DUS10_HUMAN Increases Expression [7]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Response To Substance [30]
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⏷ Show the Full List of 88 DOT(s)
Indication(s) of Miglustat
Disease Entry ICD 11 Status REF
Niemann-Pick disease type C N.A. Approved [4]
Type 1 gaucher disease 5C56.0Y Approved [5]
Gaucher disease 5C56.0Y Investigative [4]
Miglustat Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ceramide glucosyltransferase (UGCG) TTPHEX3 CEGT_HUMAN Inhibitor [31]
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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 [32]
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References

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2 Sertraline 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: 4798).
4 Miglustat FDA Label
5 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).
6 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
7 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
8 Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry. 2005 Jun;162(6):1165-70. doi: 10.1176/appi.ajp.162.6.1165.
9 Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein. Autophagy. 2021 Oct;17(10):2783-2799. doi: 10.1080/15548627.2020.1841953. Epub 2020 Nov 9.
10 Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
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12 New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients. Ther Clin Risk Manag. 2014 Jun 13;10:423-36.
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15 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA166181117)
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17 Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int J Clin Pharm. 2016 Apr;38(2):388-94.
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21 Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
22 Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
23 Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicol In Vitro. 2015 Oct;29(7):1729-35.
24 Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
25 Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
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30 The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl). 2004 Aug;174(4):525-9. doi: 10.1007/s00213-003-1562-3. Epub 2003 Sep 4.
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32 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.