Details of the Drug Combination

General Information of Drug Combination (ID: DCTHSYG)

Drug Combination Name
LIAROZOLE Fludarabine
Indication
Disease Entry Status REF
Childhood T acute lymphoblastic leukemia Investigative [1]
Component Drugs LIAROZOLE   DM4OYXE Fludarabine   DMVRLT7
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CCRF-CEM
Zero Interaction Potency (ZIP) Score: 5.2
Bliss Independence Score: 1.75
Loewe Additivity Score: 0.33
LHighest Single Agent (HSA) Score: 3.64

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LIAROZOLE
Disease Entry ICD 11 Status REF
Dermatological disease DA24.Y Phase 2/3 [2]
LIAROZOLE Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [5]
Cytochrome P450 26 (CYP26A1) TTD7Q0R CP26A_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Indication(s) of Fludarabine
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [3]
Cutaneous melanoma 2C30 Approved [3]
Haematological malignancy 2B33.Y Approved [4]
Hematologic disease 3C0Z Approved [3]
Hepatosplenic T-cell lymphoma N.A. Approved [3]
Immunodeficiency 4A00-4A85 Approved [3]
Large granular lymphocytic leukemia 2A90.1 Approved [3]
Lung cancer 2C25.0 Approved [3]
MALT lymphoma N.A. Approved [3]
Multiple sclerosis 8A40 Approved [3]
Myeloproliferative neoplasm 2A20 Approved [3]
Nodal marginal zone lymphoma 2A85.0 Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [3]
Recurrent adult burkitt lymphoma 2A85.6 Approved [3]
Small intestine lymphoma N.A. Approved [3]
Splenic marginal zone lymphoma N.A. Approved [3]
Systemic lupus erythematosus 4A40.0 Approved [3]
Systemic sclerosis 4A42 Approved [3]
Testicular lymphoma N.A. Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [3]
Colon cancer 2B90.Z Investigative [3]
Gastric cancer 2B72 Investigative [3]
Neuroblastoma 2D11.2 Investigative [3]
Fludarabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [10]
------------------------------------------------------------------------------------
Fludarabine Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Affects Expression [11]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [12]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [14]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [15]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [16]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCGH005 HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DC2BRCX MOLT-4 Investigative [1]
Astrocytoma DCKCXUL U251 Investigative [1]
Chronic myelogenous leukemia DC748U6 K-562 Investigative [1]
Clear cell renal cell carcinoma DCKO4WZ CAKI-1 Investigative [1]
Adenocarcinoma DC3VYTU OVCAR3 Investigative [17]
Pleural epithelioid mesothelioma DCKNZGE NCI-H226 Investigative [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 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: 5210).
3 Fludarabine FDA Label
4 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: 4802).
5 Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
6 Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
7 Role of histone deacetylase inhibitor-induced reactive oxygen species and DNA damage in LAQ-824/fludarabine antileukemic interactions. Mol Cancer Ther. 2008 Oct;7(10):3285-97. doi: 10.1158/1535-7163.MCT-08-0385.
8 9-beta-D-arabinofuranosyl-2-fluoroadenine inhibits expression of vascular endothelial growth factor through hypoxia-inducible factor-1 in human ovarian cancer cells. Mol Pharmacol. 2004 Jul;66(1):178-86. doi: 10.1124/mol.66.1.178.
9 MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood. 2006 May 15;107(10):4109-14. doi: 10.1182/blood-2005-08-3273. Epub 2006 Jan 26.
10 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
11 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
12 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
13 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
14 Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006 May 15;107(10):4122-9. doi: 10.1182/blood-2005-11-4465. Epub 2006 Jan 26.
15 Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 2012 Mar;107(6):781-90. doi: 10.1017/S0007114511003631. Epub 2011 Aug 1.
16 Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide. PLoS One. 2014 Jun 23;9(6):e99993. doi: 10.1371/journal.pone.0099993. eCollection 2014.
17 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976