General Information of Drug Combination (ID: DCPS156)

Drug Combination Name
IMD-0354 YM155
Indication
Disease Entry Status REF
Hodgkin lymphoma Investigative [1]
Component Drugs IMD-0354   DMOFSLE YM155   DM5Q1W4
Small molecular drug 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: 7.301
Bliss Independence Score: 4.819
Loewe Additivity Score: 0.984
LHighest Single Agent (HSA) Score: 3.513

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of IMD-0354
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Phase 1 [2]
IMD-0354 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Inhibitor of nuclear factor kappa-B kinase beta (IKKB) TTJ3E9X IKKB_HUMAN Inhibitor [4]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
⏷ 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 Activation of histamine H4 receptor inhibits TNFalpha/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells. Apoptosis. 2014 Dec;19(12):1702-11.
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 I B kinase beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. Clin Exp Allergy. 2011 Jan;41(1):104-15.
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.