General Information of Drug Combination (ID: DC5SGO6)

Drug Combination Name
Cladribine Venetoclax
Indication
Disease Entry Status REF
Acute Myeloid Leukemia Phase 2 [1]
Component Drugs Cladribine   DM3JDRP 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 Cladribine
Disease Entry ICD 11 Status REF
Hairy cell leukaemia 2A82.2 Approved [2]
Multiple sclerosis 8A40 Phase 3 [3]
Relapsing-remitting multiple sclerosis 8A40.0 Phase 3 [4]
Cladribine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [6]
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Cladribine Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [8]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [8]
Equilibrative nucleoside transporter 3 (SLC29A3) DTZAWTH S29A3_HUMAN Substrate [9]
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Cladribine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Deoxycytidine kinase (DCK) DE9FGNK DCK_HUMAN Metabolism [10]
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Cladribine Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [12]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [13]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [14]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [14]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Increases Cleavage [14]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [15]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Increases Phosphorylation [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [17]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [17]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Increases Activity [17]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [15]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [17]
Histone-lysine N-methyltransferase 2A (KMT2A) OT9GLJI6 KMT2A_HUMAN Increases Response To Substance [19]
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⏷ Show the Full List of 17 DOT(s)
Indication(s) of Venetoclax
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [5]
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 [20]
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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 [21]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Activity [22]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [23]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [21]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Folding [24]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [24]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [23]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [24]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Affects Folding [24]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Binding [25]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Affects Response To Substance [26]
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⏷ 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
Acute Myeloid Leukemia DCSF8IM N. A. Phase 2 [1]
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References

1 ClinicalTrials.gov (NCT06232655) Cladribine Venetoclax in Monocytic AML
2 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: 4799).
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
7 Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102.
8 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
9 Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem. 2005 Apr 22;280(16):15880-7.
10 Potential mechanisms of action related to the efficacy and safety of cladribine. Mult Scler Relat Disord. 2019 May;30:176-186.
11 Expression and release of chemokines associated with apoptotic cell death in human promonocytic U937 cells and peripheral blood mononuclear cells. Eur J Immunol. 1999 Oct;29(10):3225-35. doi: 10.1002/(SICI)1521-4141(199910)29:10<3225::AID-IMMU3225>3.0.CO;2-0.
12 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
13 Paradoxical immunologic effects of 2-CdA therapy: comment on the article by Davis et al. Arthritis Rheum. 1998 Sep;41(9):1704-5. doi: 10.1002/1529-0131(199809)41:9<1704::AID-ART26>3.0.CO;2-9.
14 2-Chlorodeoxyadenosine alone and in combination with cyclophosphamide and mitoxantrone induce apoptosis in B chronic lymphocytic leukemia cells in vivo. Cancer Detect Prev. 2004;28(6):433-42. doi: 10.1016/j.cdp.2004.08.001.
15 Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 2012 Mar;107(6):781-90. doi: 10.1017/S0007114511003631. Epub 2011 Aug 1.
16 Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma. BMC Cancer. 2011 Jun 16;11:255. doi: 10.1186/1471-2407-11-255.
17 Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mitochondria. Biochem J. 2001 Nov 1;359(Pt 3):537-46. doi: 10.1042/0264-6021:3590537.
18 Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol. 2003 Sep 1;66(5):711-24. doi: 10.1016/s0006-2952(03)00410-6.
19 In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype. Leukemia. 2004 Mar;18(3):521-9. doi: 10.1038/sj.leu.2403253.
20 Venclexta FDA label
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.