Details of the Drug Combination

General Information of Drug Combination (ID: DCE5NQG)

Drug Combination Name
PMID25656651-Compound-5 CP-673451
Indication
Disease Entry Status REF
Hodgkin lymphoma Investigative [1]
Component Drugs PMID25656651-Compound-5   DMAI95U CP-673451   DMVBPRO
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: L-1236
Zero Interaction Potency (ZIP) Score: 44.749
Bliss Independence Score: 44.36
Loewe Additivity Score: 0.71
LHighest Single Agent (HSA) Score: 4.685

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 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [5]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Activity [5]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [6]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Activity [4]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [6]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Cleavage [7]
High affinity nerve growth factor receptor (NTRK1) OTJORQAU NTRK1_HUMAN Decreases Activity [4]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Activity [4]
Tyrosine-protein kinase Fyn (FYN) OTLSLVZS FYN_HUMAN Decreases Activity [4]
Tyrosine-protein kinase Lyn (LYN) OTP686K2 LYN_HUMAN Decreases Activity [4]
Tyrosine-protein kinase HCK (HCK) OTRL6OSI HCK_HUMAN Decreases Activity [4]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [8]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Activity [4]
Troponin I, cardiac muscle (TNNI3) OT65E12V TNNI3_HUMAN Increases Secretion [9]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Decreases Activity [4]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [6]
Tyrosine-protein kinase FRK (FRK) OTEKV1SC FRK_HUMAN Decreases Activity [4]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [9]
Tyrosine-protein kinase Blk (BLK) OT1EB8MT BLK_HUMAN Decreases Activity [4]
Cytoplasmic tyrosine-protein kinase BMX (BMX) OTJUE0ZD BMX_HUMAN Decreases Activity [4]
Tyrosine-protein kinase JAK3 (JAK3) OTQ8QW2L JAK3_HUMAN Decreases Activity [4]
Protein-tyrosine kinase 6 (PTK6) OT7NWIQ0 PTK6_HUMAN Decreases Activity [4]
Protein-tyrosine kinase 2-beta (PTK2B) OTGAS0I8 FAK2_HUMAN Decreases Activity [4]
Receptor tyrosine-protein kinase erbB-4 (ERBB4) OT9L6C41 ERBB4_HUMAN Decreases Activity [4]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Increases Lipidation [11]
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⏷ Show the Full List of 27 DOT(s)
Indication(s) of CP-673451
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [3]
CP-673451 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Platelet-derived growth factor receptor alpha (PDGFRA) TT8FYO9 PGFRA_HUMAN Inhibitor [3]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Inhibitor [3]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Inhibitor [3]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
3 Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res. 2005 Feb 1;65(3):957-66.
4 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.
5 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.
6 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.
7 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.
8 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.
9 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.
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.