Details of the Drug Combination

General Information of Drug Combination (ID: DCHNM7Y)

Drug Combination Name
Fludarabine Ibrutinib
Indication
Disease Entry Status REF
Chronic Lymphocytic Leukemia Phase 2 [1]
Component Drugs Fludarabine   DMVRLT7 Ibrutinib   DMHZCPO
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 Fludarabine
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [2]
Cutaneous melanoma 2C30 Approved [2]
Haematological malignancy 2B33.Y Approved [3]
Hematologic disease 3C0Z Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [2]
Immunodeficiency 4A00-4A85 Approved [2]
Large granular lymphocytic leukemia 2A90.1 Approved [2]
Lung cancer 2C25.0 Approved [2]
MALT lymphoma N.A. Approved [2]
Multiple sclerosis 8A40 Approved [2]
Myeloproliferative neoplasm 2A20 Approved [2]
Nodal marginal zone lymphoma 2A85.0 Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [2]
Recurrent adult burkitt lymphoma 2A85.6 Approved [2]
Small intestine lymphoma N.A. Approved [2]
Splenic marginal zone lymphoma N.A. Approved [2]
Systemic lupus erythematosus 4A40.0 Approved [2]
Systemic sclerosis 4A42 Approved [2]
Testicular lymphoma N.A. Approved [2]
Classic Hodgkin lymphoma N.A. Investigative [2]
Colon cancer 2B90.Z Investigative [2]
Gastric cancer 2B72 Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Fludarabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [11]
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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 [12]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [8]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [14]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [15]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [16]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [17]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [10]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Ibrutinib
Disease Entry ICD 11 Status REF
Mantle cell lymphoma 2A85.5 Approved [4]
Small lymphocytic lymphoma 2A82.0 Approved [5]
Waldenstrom macroglobulinemia 2A85.4 Approved [5]
B-cell non-hodgkin lymphoma 2B33.5 Phase 3 [6]
Diffuse large B-cell lymphoma 2A81 Phase 3 [6]
Follicular lymphoma 2A80 Phase 3 [6]
Non-hodgkin lymphoma 2B33.5 Phase 3 [6]
Pancreatic cancer 2C10 Phase 3 [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [7]
Solid tumour/cancer 2A00-2F9Z Phase 2 [6]
Ibrutinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase BTK (ATK) TTGM6VW BTK_HUMAN Inhibitor [18]
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Ibrutinib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [19]
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Ibrutinib Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [20]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [20]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [20]
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Ibrutinib Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [21]
PR domain zinc finger protein 1 (PRDM1) OTQLSVBS PRDM1_HUMAN Decreases Expression [21]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2) OTGVC9MY PLCG2_HUMAN Decreases Phosphorylation [21]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) OTVLI4DD TNAP3_HUMAN Decreases Expression [21]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [21]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [21]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [21]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [22]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Response To Substance [21]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Decreases Response To Substance [21]
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14) OTT3DOOL M3K14_HUMAN Decreases Response To Substance [21]
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⏷ Show the Full List of 11 DOT(s)

References

1 ClinicalTrials.gov (NCT02514083) A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL
2 Fludarabine FDA Label
3 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).
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: 6912).
5 Ibrutinib FDA Label
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization
8 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.
9 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.
10 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.
11 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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. (Target id: 1948).
19 P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability. Mol Pharm. 2018 Nov 5;15(11):5124-5134.
20 Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97.
21 Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
22 Label-Free Bottom-Up Proteomic Workflow for Simultaneously Assessing the Target Specificity of Covalent Drug Candidates and Their Off-Target Reactivity to Selected Proteins. Chem Res Toxicol. 2016 Jan 19;29(1):109-16. doi: 10.1021/acs.chemrestox.5b00460. Epub 2015 Dec 29.