Details of the Drug Combination

General Information of Drug Combination (ID: DCA4EJ0)

Drug Combination Name
Duvelisib Venetoclax
Indication
Disease Entry Status REF
Chronic Lymphocytic Leukemia Phase 1 [1]
Component Drugs Duvelisib   DM7USVA Venetoclax   DM8I94Y
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 Duvelisib
Disease Entry ICD 11 Status REF
Follicular lymphoma 2A80 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [3]
Duvelisib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN PI3-kinase delta (PIK3CD) TTK5FVJ PK3CD_HUMAN Inhibitor [3]
HUMAN PI3-kinase gamma (PIK3CG) TTHXGLJ PK3CG_HUMAN Inhibitor [3]
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Duvelisib Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Activator of apoptosis harakiri (HRK) OTR4GWJ0 HRK_HUMAN Increases Expression [5]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [5]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [5]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Decreases Expression [5]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [5]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [5]
Bcl-2-like protein 13 (BCL2L13) OT2VRFTM B2L13_HUMAN Increases Expression [5]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Venetoclax
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [4]
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 [6]
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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 [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [8]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [10]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [9]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [10]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [10]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [11]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [12]
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⏷ Show the Full List of 11 DOT(s)

References

1 ClinicalTrials.gov (NCT02640833) A Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 211155
3 ClinicalTrials.gov (NCT04372602) Duvelisib to Combat COVID-19. U.S. National Institutes of Health.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199). Leukemia. 2017 Sep;31(9):1872-1881. doi: 10.1038/leu.2016.382. Epub 2016 Dec 26.
6 Venclexta FDA label
7 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.
8 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.
9 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.
10 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.
11 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.
12 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.