Details of the Drug Combination

General Information of Drug Combination (ID: DCMVINI)

Drug Combination Name
PMID25656651-Compound-5 PMID25656651-Compound-5
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs PMID25656651-Compound-5   DMAI95U PMID25656651-Compound-5   DMAI95U
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: Rh36
Zero Interaction Potency (ZIP) Score: 6.984
Bliss Independence Score: 9.655
Loewe Additivity Score: 6.743
LHighest Single Agent (HSA) Score: 6.084

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PMID25656651-Compound-5
Disease Entry ICD 11 Status REF
Chronic myeloid leukaemia 2A20 Patented [2]
PMID25656651-Compound-5 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Inhibitor [2]
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PMID25656651-Compound-5 Interacts with 68 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [4]
Macrophage colony-stimulating factor 1 receptor (CSF1R) OTDYTB9C CSF1R_HUMAN Decreases Activity [4]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [4]
Platelet-derived growth factor receptor beta (PDGFRB) OTYSNK9Q PGFRB_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Activity [4]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [4]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [4]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 4 (FGFR4) OTRQERG2 FGFR4_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Activity [4]
Ephrin type-A receptor 2 (EPHA2) OTI6QNX2 EPHA2_HUMAN Decreases Activity [4]
Ephrin type-A receptor 3 (EPHA3) OTZJF3ML EPHA3_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 3 (FLT4) OTRAA26B VGFR3_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Activity [4]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Activity [4]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Activity [4]
Ephrin type-A receptor 7 (EPHA7) OT3VC211 EPHA7_HUMAN Decreases Activity [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [5]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Activity [3]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [3]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [5]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Cleavage [6]
High affinity nerve growth factor receptor (NTRK1) OTJORQAU NTRK1_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Fyn (FYN) OTLSLVZS FYN_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Lyn (LYN) OTP686K2 LYN_HUMAN Decreases Activity [3]
Tyrosine-protein kinase HCK (HCK) OTRL6OSI HCK_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Fgr (FGR) OTCUYU9F FGR_HUMAN Decreases Activity [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [5]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Activity [3]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [3]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [5]
Troponin I, cardiac muscle (TNNI3) OT65E12V TNNI3_HUMAN Increases Secretion [8]
Ephrin type-A receptor 1 (EPHA1) OTGJMRZ0 EPHA1_HUMAN Decreases Activity [3]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Decreases Activity [3]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Ephrin type-A receptor 8 (EPHA8) OTHOESG6 EPHA8_HUMAN Decreases Activity [3]
Ephrin type-B receptor 2 (EPHB2) OT8VZ6C5 EPHB2_HUMAN Decreases Activity [3]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [5]
Tyrosine-protein kinase CSK (CSK) OTP03OD0 CSK_HUMAN Decreases Activity [3]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Phosphorylation [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Tyrosine-protein kinase ABL2 (ABL2) OTS8F4GD ABL2_HUMAN Decreases Activity [3]
Tyrosine-protein kinase FRK (FRK) OTEKV1SC FRK_HUMAN Decreases Activity [3]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [8]
Tyrosine-protein kinase Blk (BLK) OT1EB8MT BLK_HUMAN Decreases Activity [3]
Cytoplasmic tyrosine-protein kinase BMX (BMX) OTJUE0ZD BMX_HUMAN Decreases Activity [3]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Activity [3]
Ephrin type-B receptor 3 (EPHB3) OT4XD8O3 EPHB3_HUMAN Decreases Activity [3]
Ephrin type-A receptor 5 (EPHA5) OTAM0CVX EPHA5_HUMAN Decreases Activity [3]
Ephrin type-B receptor 4 (EPHB4) OTKLPVXJ EPHB4_HUMAN Decreases Activity [3]
Ephrin type-B receptor 1 (EPHB1) OTPG2DRZ EPHB1_HUMAN Decreases Activity [3]
Ephrin type-A receptor 4 (EPHA4) OT3AMK0C EPHA4_HUMAN Decreases Activity [3]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [5]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [10]
Protein-tyrosine kinase 6 (PTK6) OT7NWIQ0 PTK6_HUMAN Decreases Activity [3]
Protein-tyrosine kinase 2-beta (PTK2B) OTGAS0I8 FAK2_HUMAN Decreases Activity [3]
Receptor tyrosine-protein kinase erbB-4 (ERBB4) OT9L6C41 ERBB4_HUMAN Decreases Activity [3]
NT-3 growth factor receptor (NTRK3) OTII30MY NTRK3_HUMAN Decreases Activity [3]
BDNF/NT-3 growth factors receptor (NTRK2) OTD557PU NTRK2_HUMAN Decreases Activity [3]
Discoidin domain-containing receptor 2 (DDR2) OT9IHOGZ DDR2_HUMAN Decreases Activity [3]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Increases Lipidation [11]
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⏷ Show the Full List of 68 DOT(s)
Indication(s) of PMID25656651-Compound-5
Disease Entry ICD 11 Status REF
Chronic myeloid leukaemia 2A20 Patented [2]
PMID25656651-Compound-5 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Inhibitor [2]
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PMID25656651-Compound-5 Interacts with 68 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [4]
Macrophage colony-stimulating factor 1 receptor (CSF1R) OTDYTB9C CSF1R_HUMAN Decreases Activity [4]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [4]
Platelet-derived growth factor receptor beta (PDGFRB) OTYSNK9Q PGFRB_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Activity [4]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [4]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [4]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 4 (FGFR4) OTRQERG2 FGFR4_HUMAN Decreases Activity [4]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Activity [4]
Ephrin type-A receptor 2 (EPHA2) OTI6QNX2 EPHA2_HUMAN Decreases Activity [4]
Ephrin type-A receptor 3 (EPHA3) OTZJF3ML EPHA3_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 3 (FLT4) OTRAA26B VGFR3_HUMAN Decreases Activity [4]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Activity [4]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Activity [4]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Activity [4]
Ephrin type-A receptor 7 (EPHA7) OT3VC211 EPHA7_HUMAN Decreases Activity [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [5]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Activity [3]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [3]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [5]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Cleavage [6]
High affinity nerve growth factor receptor (NTRK1) OTJORQAU NTRK1_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Fyn (FYN) OTLSLVZS FYN_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Lyn (LYN) OTP686K2 LYN_HUMAN Decreases Activity [3]
Tyrosine-protein kinase HCK (HCK) OTRL6OSI HCK_HUMAN Decreases Activity [3]
Tyrosine-protein kinase Fgr (FGR) OTCUYU9F FGR_HUMAN Decreases Activity [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [5]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Activity [3]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [3]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [5]
Troponin I, cardiac muscle (TNNI3) OT65E12V TNNI3_HUMAN Increases Secretion [8]
Ephrin type-A receptor 1 (EPHA1) OTGJMRZ0 EPHA1_HUMAN Decreases Activity [3]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Decreases Activity [3]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Ephrin type-A receptor 8 (EPHA8) OTHOESG6 EPHA8_HUMAN Decreases Activity [3]
Ephrin type-B receptor 2 (EPHB2) OT8VZ6C5 EPHB2_HUMAN Decreases Activity [3]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [5]
Tyrosine-protein kinase CSK (CSK) OTP03OD0 CSK_HUMAN Decreases Activity [3]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Phosphorylation [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Tyrosine-protein kinase ABL2 (ABL2) OTS8F4GD ABL2_HUMAN Decreases Activity [3]
Tyrosine-protein kinase FRK (FRK) OTEKV1SC FRK_HUMAN Decreases Activity [3]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [8]
Tyrosine-protein kinase Blk (BLK) OT1EB8MT BLK_HUMAN Decreases Activity [3]
Cytoplasmic tyrosine-protein kinase BMX (BMX) OTJUE0ZD BMX_HUMAN Decreases Activity [3]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Activity [3]
Ephrin type-B receptor 3 (EPHB3) OT4XD8O3 EPHB3_HUMAN Decreases Activity [3]
Ephrin type-A receptor 5 (EPHA5) OTAM0CVX EPHA5_HUMAN Decreases Activity [3]
Ephrin type-B receptor 4 (EPHB4) OTKLPVXJ EPHB4_HUMAN Decreases Activity [3]
Ephrin type-B receptor 1 (EPHB1) OTPG2DRZ EPHB1_HUMAN Decreases Activity [3]
Ephrin type-A receptor 4 (EPHA4) OT3AMK0C EPHA4_HUMAN Decreases Activity [3]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [5]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [10]
Protein-tyrosine kinase 6 (PTK6) OT7NWIQ0 PTK6_HUMAN Decreases Activity [3]
Protein-tyrosine kinase 2-beta (PTK2B) OTGAS0I8 FAK2_HUMAN Decreases Activity [3]
Receptor tyrosine-protein kinase erbB-4 (ERBB4) OT9L6C41 ERBB4_HUMAN Decreases Activity [3]
NT-3 growth factor receptor (NTRK3) OTII30MY NTRK3_HUMAN Decreases Activity [3]
BDNF/NT-3 growth factors receptor (NTRK2) OTD557PU NTRK2_HUMAN Decreases Activity [3]
Discoidin domain-containing receptor 2 (DDR2) OT9IHOGZ DDR2_HUMAN Decreases Activity [3]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Increases Lipidation [11]
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⏷ Show the Full List of 68 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DCUZZEQ CTR Investigative [1]
Embryonal rhabdomyosarcoma DC5Y3GW RD Investigative [1]
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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 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
3 AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028.
4 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8.
5 BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther. 2014 Oct;13(10):2315-27. doi: 10.1158/1535-7163.MCT-14-0258. Epub 2014 Jul 22.
6 Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome. Haematologica. 2013 Jan;98(1):103-6. doi: 10.3324/haematol.2012.066407. Epub 2012 Aug 8.
7 Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther. 2011 Jun;10(6):1028-35. doi: 10.1158/1535-7163.MCT-10-1044. Epub 2011 Apr 11.
8 A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicol Sci. 2015 Jan;143(1):147-55. doi: 10.1093/toxsci/kfu215. Epub 2014 Oct 10.
9 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
10 Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation. Br J Haematol. 2012 May;157(4):483-92. doi: 10.1111/j.1365-2141.2012.09085.x. Epub 2012 Mar 13.
11 Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib, regorafenib and sorafenib in human hepatic HepG2 cells. Toxicology. 2018 Feb 15;395:34-44. doi: 10.1016/j.tox.2018.01.005. Epub 2018 Jan 16.