General Information of Drug Combination (ID: DCASDHE)

Drug Combination Name
Levetiracetam Fludarabine
Indication
Disease Entry Status REF
Hematologic Disorders Phase 1 [1]
Component Drugs Levetiracetam   DMTGDN8 Fludarabine   DMVRLT7
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Levetiracetam
Disease Entry ICD 11 Status REF
Epilepsy 8A60-8A68 Approved [2]
Fibromyalgia MG30.01 Approved [3]
Levetiracetam Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 3A receptor (HTR3A) TTPC4TU 5HT3A_HUMAN Antagonist [3]
Synaptic vesicle glycoprotein 2A (SV2A) TTT3P91 SV2A_HUMAN Modulator [6]
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Levetiracetam Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Levetiracetam Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [8]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Expression [9]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Expression [9]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2) OT02MSKN 3BHS2_HUMAN Decreases Expression [9]
Steroidogenic acute regulatory protein, mitochondrial (STAR) OTFEZ5AI STAR_HUMAN Decreases Expression [9]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Affects Activity [10]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Fludarabine
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [4]
Cutaneous melanoma 2C30 Approved [4]
Haematological malignancy 2B33.Y Approved [5]
Hematologic disease 3C0Z Approved [4]
Hepatosplenic T-cell lymphoma N.A. Approved [4]
Immunodeficiency 4A00-4A85 Approved [4]
Large granular lymphocytic leukemia 2A90.1 Approved [4]
Lung cancer 2C25.0 Approved [4]
MALT lymphoma N.A. Approved [4]
Multiple sclerosis 8A40 Approved [4]
Myeloproliferative neoplasm 2A20 Approved [4]
Nodal marginal zone lymphoma 2A85.0 Approved [4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [4]
Recurrent adult burkitt lymphoma 2A85.6 Approved [4]
Small intestine lymphoma N.A. Approved [4]
Splenic marginal zone lymphoma N.A. Approved [4]
Systemic lupus erythematosus 4A40.0 Approved [4]
Systemic sclerosis 4A42 Approved [4]
Testicular lymphoma N.A. Approved [4]
Classic Hodgkin lymphoma N.A. Investigative [4]
Colon cancer 2B90.Z Investigative [4]
Gastric cancer 2B72 Investigative [4]
Neuroblastoma 2D11.2 Investigative [4]
Fludarabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [14]
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Fludarabine Interacts with 22 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 [15]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [16]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [16]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [17]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Increases Expression [18]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [11]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [19]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [20]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [12]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Activity [21]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Increases Activity [21]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [19]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [20]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Increases Activity [21]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [18]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [18]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [19]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [12]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [13]
Growth/differentiation factor 15 (GDF15) OTWQN50N GDF15_HUMAN Increases Expression [17]
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⏷ Show the Full List of 22 DOT(s)

References

1 ClinicalTrials.gov (NCT01666080) Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)
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: 6826).
3 Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
4 Fludarabine FDA Label
5 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).
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46.
8 Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
9 Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model. Acta Neurol Scand Suppl. 2009;(189):14-21.
10 Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
11 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.
12 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.
13 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.
14 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Res. 2004 Apr 1;64(7):2590-600. doi: 10.1158/0008-5472.can-03-2631.