General Information of Drug Combination (ID: DCKWOXA)

Drug Combination Name
PHA-739358 Sertraline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PHA-739358   DMGYBZI 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: 2.53
Bliss Independence Score: 2.53
Loewe Additivity Score: 16.75
LHighest Single Agent (HSA) Score: 16.77

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PHA-739358
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Phase 2 [2]
PHA-739358 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [5]
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [6]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
PHA-739358 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [7]
------------------------------------------------------------------------------------
Indication(s) of Sertraline
Disease Entry ICD 11 Status REF
Coronary heart disease BA80.Z Approved [3]
Depression 6A70-6A7Z Approved [4]
Epilepsy 8A60-8A68 Approved [3]
Obsessive compulsive disorder 6B20 Approved [3]
Panic disorder 6B01 Approved [3]
Post-traumatic stress disorder 6B40 Approved [3]
Sertraline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [12]
------------------------------------------------------------------------------------
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 [13]
------------------------------------------------------------------------------------
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 [14]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [15]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [16]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [17]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [18]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [19]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [19]
------------------------------------------------------------------------------------
⏷ 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 [20]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [21]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [22]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Activity [23]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Increases Expression [8]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [8]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [8]
Serine protease hepsin (HPN) OT7QNA61 HEPS_HUMAN Increases Expression [8]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [8]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [8]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [8]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Increases Expression [8]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [8]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [8]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [8]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [8]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [8]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [8]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [8]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [24]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Expression [24]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [25]
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13) OTS93BTX M3K13_HUMAN Increases Expression [9]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [9]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [9]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [9]
Dual specificity protein phosphatase 14 (DUSP14) OTGODFCR DUS14_HUMAN Increases Expression [9]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) OTBMJUOC M4K4_HUMAN Decreases Expression [9]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [9]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [9]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [9]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [26]
Alpha-crystallin A chain (CRYAA) OTSN7JUR CRYAA_HUMAN Increases Expression [9]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [27]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [28]
Platelet factor 4 (PF4) OTEMJU68 PLF4_HUMAN Decreases Expression [10]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [9]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [9]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Increases Expression [29]
Monocyte differentiation antigen CD14 (CD14) OT83GJ47 CD14_HUMAN Decreases Expression [9]
Heat shock 70 kDa protein 1A (HSPA1A) OTKGIE76 HS71A_HUMAN Increases Expression [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [26]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [9]
Cyclic AMP-dependent transcription factor ATF-2 (ATF2) OTNIZPEA ATF2_HUMAN Increases Expression [9]
P-selectin (SELP) OTWR90PK LYAM3_HUMAN Decreases Expression [28]
Platelet endothelial cell adhesion molecule (PECAM1) OTXOM4D9 PECA1_HUMAN Decreases Expression [10]
E-selectin (SELE) OT33RZWY LYAM2_HUMAN Decreases Expression [28]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Decreases Expression [9]
Heat shock 70 kDa protein 6 (HSPA6) OTH4S7WB HSP76_HUMAN Increases Expression [9]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [9]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [11]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [26]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [26]
Dual specificity protein phosphatase 1 (DUSP1) OTN6BR75 DUS1_HUMAN Increases Expression [9]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) OTOZTA1F M3K8_HUMAN Increases Expression [9]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [9]
Translocon-associated protein subunit beta (SSR2) OTQJSL7M SSRB_HUMAN Increases Expression [9]
Caspase-4 (CASP4) OTVQTV1L CASP4_HUMAN Increases Cleavage [9]
Ribosomal protein S6 kinase alpha-3 (RPS6KA3) OTYJNNMD KS6A3_HUMAN Decreases Expression [9]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [9]
Protein transport protein Sec61 subunit gamma (SEC61G) OT7MJRXY SC61G_HUMAN Decreases Expression [9]
E3 ubiquitin-protein ligase RBX1 (RBX1) OTYA1UIO RBX1_HUMAN Decreases Expression [9]
S-phase kinase-associated protein 1 (SKP1) OT5BPAZ4 SKP1_HUMAN Decreases Expression [9]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [9]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [26]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [30]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [11]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [9]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [11]
Cullin-1 (CUL1) OTXPE1UZ CUL1_HUMAN Decreases Expression [9]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [9]
Serine/threonine-protein kinase STK11 (STK11) OT1YZSP3 STK11_HUMAN Increases Phosphorylation [11]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [9]
E3 ubiquitin-protein ligase synoviolin (SYVN1) OTZ4ZJP5 SYVN1_HUMAN Increases Expression [9]
Dual specificity protein phosphatase 16 (DUSP16) OTK7S078 DUS16_HUMAN Increases Expression [9]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [11]
DnaJ homolog subfamily C member 5 (DNAJC5) OTCZDXAL DNJC5_HUMAN Increases Expression [31]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [9]
Serine/threonine-protein kinase TAO2 (TAOK2) OTNUMOZ1 TAOK2_HUMAN Increases Expression [9]
C-Jun-amino-terminal kinase-interacting protein 3 (MAPK8IP3) OT0X8ACY JIP3_HUMAN Increases Expression [9]
Dual specificity protein phosphatase 10 (DUSP10) OTNG467B DUS10_HUMAN Increases Expression [9]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Increases Response To Substance [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 88 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: 7937).
3 Sertraline FDA Label
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: 4798).
5 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
6 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
7 Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.
8 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.
9 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.
10 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.
11 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.
12 Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
13 Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
14 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.
15 The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. CNS Drug Rev. 2001 Spring;7(1):1-24.
16 Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004 Jan-Feb;59(1):5-12.
17 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA166181117)
18 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.
19 Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int J Clin Pharm. 2016 Apr;38(2):388-94.
20 Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
21 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.
22 Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther. 2001 Jul;70(1):42-7.
23 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.
24 Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
25 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.
26 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.
27 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.
28 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.
29 Impact of selective serotonin reuptake inhibitors on neural crest stem cell formation. Toxicol Lett. 2017 Nov 5;281:20-25. doi: 10.1016/j.toxlet.2017.08.012. Epub 2017 Aug 24.
30 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
31 Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex. Neurosci Lett. 2001 Apr 6;301(3):183-6. doi: 10.1016/s0304-3940(01)01638-x.
32 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.