General Information of Drug Combination (ID: DC11I9L)

Drug Combination Name
Hydralazine Sertraline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Hydralazine   DMU8JGH Sertraline   DM0FB1J
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: 6.7
Bliss Independence Score: 6.7
Loewe Additivity Score: 18.21
LHighest Single Agent (HSA) Score: 18.21

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Hydralazine
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Malignant essential hypertension BA00 Approved [2]
Hydralazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Membrane copper amine oxidase (AOC3) TT7HC21 AOC3_HUMAN Modulator [6]
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Hydralazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Metabolism [7]
N-acetyltransferase 1 (NAT1) DE7OAB3 ARY1_HUMAN Metabolism [8]
N-acetyltransferase 2 (NAT2) DER7TA0 ARY2_HUMAN Metabolism [8]
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Hydralazine Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Increases Acetylation [9]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Increases Expression [10]
Adenomatous polyposis coli protein (APC) OTKV0TIK APC_HUMAN Decreases Methylation [10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Methylation [10]
Bis(5'-adenosyl)-triphosphatase (FHIT) OTGWBSLA FHIT_HUMAN Increases Expression [10]
Death-associated protein kinase 1 (DAPK1) OTNCNUCO DAPK1_HUMAN Increases Expression [10]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [11]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [12]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [13]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Sertraline
Disease Entry ICD 11 Status REF
Coronary heart disease BA80.Z Approved [4]
Depression 6A70-6A7Z Approved [5]
Epilepsy 8A60-8A68 Approved [4]
Obsessive compulsive disorder 6B20 Approved [4]
Panic disorder 6B01 Approved [4]
Post-traumatic stress disorder 6B40 Approved [4]
Sertraline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [18]
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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 [19]
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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 [20]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [21]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [22]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [23]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [24]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [25]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [25]
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⏷ Show the Full List of 7 DME(s)
Sertraline Interacts with 55 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [26]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [27]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Increases Expression [14]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [14]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [14]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [14]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [14]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [14]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [14]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [14]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [14]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [14]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13) OTS93BTX M3K13_HUMAN Increases Expression [15]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [15]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [15]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [15]
Dual specificity protein phosphatase 14 (DUSP14) OTGODFCR DUS14_HUMAN Increases Expression [15]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) OTBMJUOC M4K4_HUMAN Decreases Expression [15]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [15]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [15]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [28]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [29]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [15]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [15]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Increases Expression [30]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [15]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2) OTNIZPEA ATF2_HUMAN Increases Expression [15]
Heat shock 70 kDa protein 6 (HSPA6) OTH4S7WB HSP76_HUMAN Increases Expression [15]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [15]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [15]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [15]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [15]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [31]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [31]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [15]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) OTOZTA1F M3K8_HUMAN Increases Expression [15]
Translocon-associated protein subunit beta (SSR2) OTQJSL7M SSRB_HUMAN Increases Expression [15]
Protein transport protein Sec61 subunit gamma (SEC61G) OT7MJRXY SC61G_HUMAN Decreases Expression [15]
E3 ubiquitin-protein ligase RBX1 (RBX1) OTYA1UIO RBX1_HUMAN Decreases Expression [15]
S-phase kinase-associated protein 1 (SKP1) OT5BPAZ4 SKP1_HUMAN Decreases Expression [15]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [15]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [15]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [17]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [15]
Cullin-1 (CUL1) OTXPE1UZ CUL1_HUMAN Decreases Expression [15]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [15]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Phosphorylation [17]
E3 ubiquitin-protein ligase synoviolin (SYVN1) OTZ4ZJP5 SYVN1_HUMAN Increases Expression [15]
Dual specificity protein phosphatase 16 (DUSP16) OTK7S078 DUS16_HUMAN Increases Expression [15]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [17]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [32]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [15]
Serine/threonine-protein kinase TAO2 (TAOK2) OTNUMOZ1 TAOK2_HUMAN Increases Expression [15]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3) OT0X8ACY JIP3_HUMAN Increases Expression [15]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Response To Substance [33]
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⏷ Show the Full List of 55 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Hydralazine 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: 7326).
4 Sertraline 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: 4798).
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8 N-acetyltransferase 2 genotype-dependent N-acetylation of hydralazine in human hepatocytes. Drug Metab Dispos. 2017 Dec;45(12):1276-1281.
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13 Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts. Chem Res Toxicol. 2020 Jul 20;33(7):1969-1979. doi: 10.1021/acs.chemrestox.0c00146. Epub 2020 Jun 29.
14 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.
15 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.
16 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.
17 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.
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23 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA166181117)
24 Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005 Feb;33(2):262-70.
25 Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int J Clin Pharm. 2016 Apr;38(2):388-94.
26 Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther. 2001 Jul;70(1):42-7.
27 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.
28 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.
29 Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation. 2003 Aug 26;108(8):939-44. doi: 10.1161/01.CIR.0000085163.21752.0A. Epub 2003 Aug 11.
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31 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.
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33 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.