Details of the Drug Combination

General Information of Drug Combination (ID: DCGSZY3)

Drug Combination Name
BAY 80-6946 Ibrutinib
Indication
Disease Entry Status REF
Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) Phase 1 [1]
Component Drugs BAY 80-6946   DMLOS5R 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 BAY 80-6946
Disease Entry ICD 11 Status REF
Follicular lymphoma 2A80 Approved [2]
Non-hodgkin lymphoma 2B33.5 Approved [3]
BAY 80-6946 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase delta (PIK3CD) TTGBPJE PK3CD_HUMAN Inhibitor [2]
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [2]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [7]
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BAY 80-6946 Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [8]
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BAY 80-6946 Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Response To Substance [9]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [9]
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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 [3]
Diffuse large B-cell lymphoma 2A81 Phase 3 [3]
Follicular lymphoma 2A80 Phase 3 [3]
Non-hodgkin lymphoma 2B33.5 Phase 3 [3]
Pancreatic cancer 2C10 Phase 3 [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [6]
Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
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 [10]
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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 [11]
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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 [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
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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 [13]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [14]
PR domain zinc finger protein 1 (PRDM1) OTQLSVBS PRDM1_HUMAN Decreases Expression [14]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [14]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2) OTGVC9MY PLCG2_HUMAN Decreases Phosphorylation [14]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) OTVLI4DD TNAP3_HUMAN Decreases Expression [14]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Expression [14]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Expression [14]
Polycomb complex protein BMI-1 (BMI1) OTROVLJ0 BMI1_HUMAN Decreases Expression [14]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [14]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [14]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [14]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) OT9RDS3H IKKB_HUMAN Decreases Activity [15]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [16]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [17]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Affects Binding [16]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Decreases Response To Substance [14]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Decreases Response To Substance [14]
CREB-binding protein (CREBBP) OTPA4QGM CBP_HUMAN Decreases Response To Substance [14]
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14) OTT3DOOL M3K14_HUMAN Decreases Response To Substance [14]
Serine/threonine-protein kinase pim-1 (PIM1) OTWEKXTU PIM1_HUMAN Decreases Response To Substance [14]
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⏷ Show the Full List of 21 DOT(s)

References

1 ClinicalTrials.gov (NCT03581942) Copanlisib With Ibrutinib for Patients With Recurrent/ Refractory Primary Central Nervous System Lymphoma (PCNSL)
2 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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 Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization
7 BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
8 FDA label of Copanlisib. The 2020 official website of the U.S. Food and Drug Administration.
9 PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
10 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).
11 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.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.