Details of the Drug Combination

General Information of Drug Combination (ID: DCCEDU6)

Drug Combination Name
Cladribine Cladribine
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs Cladribine   DM3JDRP Cladribine   DM3JDRP
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: JHH-136
Zero Interaction Potency (ZIP) Score: 4.38
Bliss Independence Score: 3.53
Loewe Additivity Score: 6.18
LHighest Single Agent (HSA) Score: 8.44

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 [5]
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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 [6]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [7]
Equilibrative nucleoside transporter 3 (SLC29A3) DTZAWTH S29A3_HUMAN Substrate [8]
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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 [9]
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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 [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [11]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [13]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [10]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [13]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Increases Cleavage [13]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [14]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Increases Phosphorylation [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [16]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [17]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [16]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Increases Activity [16]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [14]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [16]
Histone-lysine N-methyltransferase 2A (KMT2A) OT9GLJI6 KMT2A_HUMAN Increases Response To Substance [18]
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⏷ Show the Full List of 17 DOT(s)
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 [5]
------------------------------------------------------------------------------------
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 [6]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [7]
Equilibrative nucleoside transporter 3 (SLC29A3) DTZAWTH S29A3_HUMAN Substrate [8]
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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 [9]
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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 [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [11]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [13]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [10]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [13]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Increases Cleavage [13]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [14]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Increases Phosphorylation [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [16]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [17]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [16]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Increases Activity [16]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [14]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [16]
Histone-lysine N-methyltransferase 2A (KMT2A) OT9GLJI6 KMT2A_HUMAN Increases Response To Substance [18]
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⏷ Show the Full List of 17 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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 Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
6 Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 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.
9 Potential mechanisms of action related to the efficacy and safety of cladribine. Mult Scler Relat Disord. 2019 May;30:176-186.
10 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.
11 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.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.