General Information of Drug Combination (ID: DC3796J)

Drug Combination Name
Nintedanib Ibrutinib
Indication
Disease Entry Status REF
Diffuse large B cell lymphoma Investigative [1]
Component Drugs Nintedanib   DMMQ2OW Ibrutinib   DMHZCPO
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TMD8
Zero Interaction Potency (ZIP) Score: 18
Bliss Independence Score: 17.84
Loewe Additivity Score: 10.75
LHighest Single Agent (HSA) Score: 13.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nintedanib
Disease Entry ICD 11 Status REF
Idiopathic pulmonary fibrosis CB03.4 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [3]
Ovarian neoplasm N.A. Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Indication(s) of Ibrutinib
Disease Entry ICD 11 Status REF
Mantle cell lymphoma 2A85.5 Approved [5]
Small lymphocytic lymphoma 2A82.0 Approved [6]
Waldenstrom macroglobulinemia 2A85.4 Approved [6]
B-cell non-hodgkin lymphoma 2B33.5 Phase 3 [7]
Diffuse large B-cell lymphoma 2A81 Phase 3 [7]
Follicular lymphoma 2A80 Phase 3 [7]
Non-hodgkin lymphoma 2B33.5 Phase 3 [7]
Pancreatic cancer 2C10 Phase 3 [7]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [8]
Solid tumour/cancer 2A00-2F9Z Phase 2 [7]
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 [9]
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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 [10]
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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 [11]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [11]
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Ibrutinib Interacts with 21 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase BTK (BTK) OTG3CDVK BTK_HUMAN Decreases Response To Substance [12]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [13]
PR domain zinc finger protein 1 (PRDM1) OTQLSVBS PRDM1_HUMAN Decreases Expression [13]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [13]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2) OTGVC9MY PLCG2_HUMAN Decreases Phosphorylation [13]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) OTVLI4DD TNAP3_HUMAN Decreases Expression [13]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Expression [13]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Expression [13]
Polycomb complex protein BMI-1 (BMI1) OTROVLJ0 BMI1_HUMAN Decreases Expression [13]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [13]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [13]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [13]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) OT9RDS3H IKKB_HUMAN Decreases Activity [14]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [15]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [16]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Affects Binding [15]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Response To Substance [13]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Decreases Response To Substance [13]
CREB-binding protein (CREBBP) OTPA4QGM CBP_HUMAN Decreases Response To Substance [13]
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14) OTT3DOOL M3K14_HUMAN Decreases Response To Substance [13]
Serine/threonine-protein kinase pim-1 (PIM1) OTWEKXTU PIM1_HUMAN Decreases Response To Substance [13]
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⏷ Show the Full List of 21 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 205832
3 Nintedanib FDA Label
4 ClinicalTrials.gov (NCT04338802) Efficacy and Safety of Nintedanib in the Treatment of Pulmonary Fibrosis in Patients With Moderate to Severe COVID -19. U.S. National Institutes of Health.
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: 6912).
6 Ibrutinib FDA Label
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization
9 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).
10 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.
11 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.
12 Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors. Leukemia. 2015 Apr;29(4):895-900. doi: 10.1038/leu.2014.263. Epub 2014 Sep 5.
13 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.
14 Blockade of oncogenic IB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11365-70. doi: 10.1073/pnas.1411701111. Epub 2014 Jul 21.
15 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.
16 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.