Details of the Drug Combination

General Information of Drug Combination (ID: DCGR5B8)

Drug Combination Name
Venetoclax BAY 80-6946
Indication
Disease Entry Status REF
Non-Hodgkin Lymphoma Phase 1 [1]
Component Drugs Venetoclax   DM8I94Y BAY 80-6946   DMLOS5R
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 Venetoclax
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [2]
Venetoclax Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
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Venetoclax Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [6]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [7]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [8]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [9]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [9]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [10]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [11]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of BAY 80-6946
Disease Entry ICD 11 Status REF
Follicular lymphoma 2A80 Approved [3]
Non-hodgkin lymphoma 2B33.5 Approved [4]
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 [3]
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [3]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [12]
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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 [13]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [13]
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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 [14]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [14]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [14]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Diffuse Large B Cell Lymphoma DCTO2Z4 N. A. Phase 1 [15]
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References

1 ClinicalTrials.gov (NCT03886649) Copanlisib in Combination With Venetoclax in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Venclexta FDA label
6 ZCL-082, a boron-containing compound, induces apoptosis of non-Hodgkin's lymphoma via targeting p90 ribosomal S6 kinase 1/NF-B signaling pathway. Chem Biol Interact. 2022 Jan 5;351:109770. doi: 10.1016/j.cbi.2021.109770. Epub 2021 Nov 30.
7 Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat Genet. 2015 Sep;47(9):1020-1029. doi: 10.1038/ng.3362. Epub 2015 Jul 27.
8 HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia. Curr Issues Mol Biol. 2023 Aug 23;45(9):7011-7026. doi: 10.3390/cimb45090443.
9 Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
10 Prospective Drug Candidates as Human Multidrug Transporter ABCG2 Inhibitors: an In Silico Drug Discovery Study. Cell Biochem Biophys. 2021 Jun;79(2):189-200. doi: 10.1007/s12013-021-00985-y. Epub 2021 May 5.
11 Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors. Cancer Res Commun. 2023 Dec 8;3(12):2497-2509. doi: 10.1158/2767-9764.CRC-23-0350.
12 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.
13 FDA label of Copanlisib. The 2020 official website of the U.S. Food and Drug Administration.
14 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.
15 ClinicalTrials.gov (NCT04572763) Copanlisib Plus Venetoclax in R/R DLBCL