General Information of Drug Combination (ID: DCCG0Q9)

Drug Combination Name
Venetoclax ABT-263
Indication
Disease Entry Status REF
Myeloid Malignancy Phase 1 [1]
Component Drugs Venetoclax   DM8I94Y ABT-263   DMNE56X
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 [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)
Indication(s) of ABT-263
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Phase 3 [3]
Relapsed or refractory chronic lymphocytic leukaemia 2A82.0 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [5]
ABT-263 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-W (BCL-W) TTQ79W8 B2CL2_HUMAN Inhibitor [13]
G1/S-specific cyclin-D1 (CCND1) TTFCJ7S CCND1_HUMAN Inhibitor [14]
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Inhibitor [13]
Apoptosis regulator Bcl-xL (BCL-xL) TTU1E82 B2CL1_HUMAN Inhibitor [13]
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ABT-263 Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
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ABT-263 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [16]
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ABT-263 Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [17]
Gelsolin (GSN) OT4KS2UU GELS_HUMAN Increases Cleavage [18]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [18]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Affects Response To Substance [17]
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⏷ Show the Full List of 6 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Acute Lymphoblastic Leukemia DCJPVLH N. A. Phase 1 [19]
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References

1 ClinicalTrials.gov (NCT05455294) Combination Navitoclax, Venetoclax and Decitabine for Advanced Myeloid Neoplasms
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health.
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: 8319).
5 Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
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.
13 Clinical pipeline report, company report or official report of Roche (2009).
14 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15 The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein. Biochem Biophys Res Commun. 2011 May 6;408(2):344-9.
16 Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer. J Clin Pharm Ther. 2014 Dec;39(6):680-4.
17 Human breast cancer cells display different sensitivities to ABT-263 based on the level of survivin. Toxicol In Vitro. 2018 Feb;46:229-236. doi: 10.1016/j.tiv.2017.09.023. Epub 2017 Sep 23.
18 BCL2/BCL-X(L) inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood. 2011 Jun 30;117(26):7145-54. doi: 10.1182/blood-2011-03-344812. Epub 2011 May 11.
19 ClinicalTrials.gov (NCT05054465) A Phase 1b-2 Trial to Assess Venetoclax and Navitoclax Consolidation and Post-transplant Maintenance in High-risk Patients With T-ALL