Details of the Drug Combination

General Information of Drug Combination (ID: DCDJGS3)

Drug Combination Name
Selinexor Venetoclax
Indication
Disease Entry Status REF
Diffuse Large B-cell Lymphoma Phase 1 [1]
Component Drugs Selinexor   DMBD4K3 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 Selinexor
Disease Entry ICD 11 Status REF
Multiple myeloma 2A83 Approved [2]
Liposarcoma 2B59 Phase 3 [3]
Neuroendocrine cancer 2B72.1 Phase 3 [3]
Acute myeloid leukaemia 2A60 Phase 2 [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Diffuse large B-cell lymphoma 2A81 Phase 2 [4]
Recurrent glioblastoma 2A00.00 Phase 2 [3]
Solid tumour/cancer 2A00-2F9Z Phase 2 [6]
Selinexor Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Exportin-1 (XPO1) TTCJUR4 XPO1_HUMAN Inhibitor [7]
------------------------------------------------------------------------------------
Selinexor Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [8]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Selinexor Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor protein p73 (TP73) OT0LUO47 P73_HUMAN Increases Expression [9]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [9]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [9]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [9]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DOT(s)
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 [10]
------------------------------------------------------------------------------------
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 [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [12]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [14]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [13]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [14]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [14]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [15]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
AML DCD4CLW N. A. Phase 2 [17]
AML, Adult DCV3MVY N. A. Phase 2 [18]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT03955783) Venetoclax and Selinexor in Treating Patients With Relapsed or Refractory High Risk Hematologic Malignancies
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT04349098) Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection. U.S. National Institutes of Health.
6 ClinicalTrials.gov (NCT02025985) Phase II Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies. U.S. National Institutes of Health.
7 Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014 August; 0: 62-73.
8 FDA label of Selinexor. The 2020 official website of the U.S. Food and Drug Administration.
9 The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
10 Venclexta FDA label
11 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.
12 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.
13 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.
14 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.
15 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.
16 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.
17 ClinicalTrials.gov (NCT05736978) Adaptive Treatment for Acute Myeloid Leukemia Based on D14 MRD Results
18 ClinicalTrials.gov (NCT05736965) A Study of Selinexor in Combination With Azacitidine and Venetoclax (SAV Regimen) in Treatment Nave Participants With Acute Myeloid Leukemia