Details of the Drug Combination

General Information of Drug Combination (ID: DCBNZPM)

Drug Combination Name
YM155 AT13387
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs YM155   DM5Q1W4 AT13387   DM2B9E0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 8.807
Bliss Independence Score: 9.104
Loewe Additivity Score: 1.065
LHighest Single Agent (HSA) Score: 4.423

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of YM155
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Non-hodgkin lymphoma 2B33.5 Phase 2 [2]
YM155 Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [4]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [4]
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YM155 Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [5]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Phosphorylation [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [7]
POU domain, class 5, transcription factor 1 (POU5F1) OTDHHN7O PO5F1_HUMAN Decreases Expression [6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [7]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [7]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [7]
ELAV-like protein 1 (ELAVL1) OTY55PLY ELAV1_HUMAN Decreases Expression [7]
Histone-lysine N-methyltransferase EHMT2 (EHMT2) OTC4DWB6 EHMT2_HUMAN Decreases Expression [6]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [7]
Histone-lysine N-methyltransferase EHMT1 (EHMT1) OT6QC8GK EHMT1_HUMAN Decreases Expression [6]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Response To Substance [8]
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⏷ Show the Full List of 16 DOT(s)
Indication(s) of AT13387
Disease Entry ICD 11 Status REF
Melanoma 2C30 Phase 1 [3]
AT13387 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [9]
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AT13387 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
mRNA-capping enzyme (RNGTT) OT59E0KX MCE1_HUMAN Decreases Expression [10]
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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 ClinicalTrials.gov (NCT00818480) An Extension Study Administering YM155 to Subjects Previously Enrolled in Another Protocol Administering YM155. U.S. National Institutes of Health.
3 Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
4 Characterization of human organic cation transporter 1 (OCT1/SLC22A1)- and OCT2 (SLC22A2)-mediated transport of 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)- 4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), a novel small molecule survivin suppressant. Drug Metab Dispos. 2010 Jan;38(1):1-4.
5 Inhibition of pluripotent stem cell-derived teratoma formation by small molecules. Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):E3281-90. doi: 10.1073/pnas.1303669110. Epub 2013 Aug 5.
6 YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells. PLoS One. 2017 Aug 7;12(8):e0182149. doi: 10.1371/journal.pone.0182149. eCollection 2017.
7 Autophagic HuR mRNA degradation induces survivin and MCL1 downregulation in YM155-treated human leukemia cells. Toxicol Appl Pharmacol. 2020 Jan 15;387:114857. doi: 10.1016/j.taap.2019.114857. Epub 2019 Dec 16.
8 The SMAC mimetic LCL161 is a direct ABCB1/MDR1-ATPase activity modulator and BIRC5/Survivin expression down-regulator in cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115080. doi: 10.1016/j.taap.2020.115080. Epub 2020 Jun 1.
9 Astex Presents Updates on AT13387, its HSP90 Inhibitor, and AT9283, its Multi-Targeted Kinase Inhibitor at the EORTC-NCI-AACR Cancer Conference. Astex. 2008.
10 RNA-binding proteins and heat-shock protein 90 are constituents of the cytoplasmic capping enzyme interactome. J Biol Chem. 2018 Oct 26;293(43):16596-16607. doi: 10.1074/jbc.RA118.004973. Epub 2018 Aug 30.