Details of the Drug Combination

General Information of Drug Combination (ID: DC1POCJ)

Drug Combination Name
YM155 Everolimus
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs YM155   DM5Q1W4 Everolimus   DM8X2EH
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: 27.916
Bliss Independence Score: 28.913
Loewe Additivity Score: 9.032
LHighest Single Agent (HSA) Score: 12.061

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 [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
------------------------------------------------------------------------------------
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 [8]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Phosphorylation [9]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [10]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [10]
POU domain, class 5, transcription factor 1 (POU5F1) OTDHHN7O PO5F1_HUMAN Decreases Expression [9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [10]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [10]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [10]
ELAV-like protein 1 (ELAVL1) OTY55PLY ELAV1_HUMAN Decreases Expression [10]
Histone-lysine N-methyltransferase EHMT2 (EHMT2) OTC4DWB6 EHMT2_HUMAN Decreases Expression [9]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [10]
Histone-lysine N-methyltransferase EHMT1 (EHMT1) OT6QC8GK EHMT1_HUMAN Decreases Expression [9]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Response To Substance [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 DOT(s)
Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [3]
Advanced/metastatic breast cancer 2C60 Approved [4]
Brainstem neoplasm N.A. Approved [3]
Breast carcinoma N.A. Approved [3]
Graft-versus-host disease 4B24 Approved [3]
Intracranial meningioma N.A. Approved [3]
Leukemia N.A. Approved [3]
Lung cancer 2C25.0 Approved [3]
Mucosal melanoma N.A. Approved [3]
Multiple sclerosis 8A40 Approved [3]
Plasma cell myeloma 2A83.1 Approved [3]
Prostate cancer 2C82.0 Approved [3]
Renal cell carcinoma 2C90 Approved [5]
Salivary gland squamous cell carcinoma N.A. Approved [3]
Tuberous sclerosis LD2D.2 Approved [3]
Kidney cancer 2C90.0 Phase 3 [5]
Castration-resistant prostate carcinoma N.A. Investigative [3]
Colon cancer 2B90.Z Investigative [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [6]
Neuroblastoma 2D11.2 Investigative [3]
Pancreatic acinar cell carcinoma N.A. Investigative [3]
Polycystic kidney disease GB8Y Investigative [3]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [6]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [12]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Everolimus 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]
------------------------------------------------------------------------------------
Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
------------------------------------------------------------------------------------

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 Everolimus FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 5889).
6 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
7 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.
8 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.
9 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.
10 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.
11 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.
12 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
13 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
14 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.