Details of the Drug Combination

General Information of Drug Combination (ID: DCMIBJB)

Drug Combination Name
GDC-0084 YM155
Indication
Disease Entry Status REF
Hodgkin lymphoma Investigative [1]
Component Drugs GDC-0084   DMA9SEY YM155   DM5Q1W4
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: L-1236
Zero Interaction Potency (ZIP) Score: 4.237
Bliss Independence Score: 4.588
Loewe Additivity Score: 2.435
LHighest Single Agent (HSA) Score: 5.242

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GDC-0084
Disease Entry ICD 11 Status REF
Glioblastoma of brain 2A00.00 Phase 2 [2]
GDC-0084 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [4]
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Indication(s) of YM155
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [3]
Non-hodgkin lymphoma 2B33.5 Phase 2 [3]
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 [5]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [5]
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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 [6]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Phosphorylation [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [8]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [8]
POU domain, class 5, transcription factor 1 (POU5F1) OTDHHN7O PO5F1_HUMAN Decreases Expression [7]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [8]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [8]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [8]
ELAV-like protein 1 (ELAVL1) OTY55PLY ELAV1_HUMAN Decreases Expression [8]
Histone-lysine N-methyltransferase EHMT2 (EHMT2) OTC4DWB6 EHMT2_HUMAN Decreases Expression [7]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [8]
Histone-lysine N-methyltransferase EHMT1 (EHMT1) OT6QC8GK EHMT1_HUMAN Decreases Expression [7]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Response To Substance [9]
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⏷ Show the Full List of 16 DOT(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 ClinicalTrials.gov (NCT03522298) Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma. U.S. National Institutes of Health.
3 ClinicalTrials.gov (NCT00818480) An Extension Study Administering YM155 to Subjects Previously Enrolled in Another Protocol Administering YM155. U.S. National Institutes of Health.
4 Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.
5 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.
6 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.
7 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.
8 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.
9 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.