Details of the Drug Combination

General Information of Drug Combination (ID: DCKC5EJ)

Drug Combination Name
Fludarabine CATECHIN
Indication
Disease Entry Status REF
Hematological Malignancies Phase 1 [1]
Component Drugs Fludarabine   DMVRLT7 CATECHIN   DMY38SB
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 Fludarabine
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [2]
Cutaneous melanoma 2C30 Approved [2]
Haematological malignancy 2B33.Y Approved [3]
Hematologic disease 3C0Z Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [2]
Immunodeficiency 4A00-4A85 Approved [2]
Large granular lymphocytic leukemia 2A90.1 Approved [2]
Lung cancer 2C25.0 Approved [2]
MALT lymphoma N.A. Approved [2]
Multiple sclerosis 8A40 Approved [2]
Myeloproliferative neoplasm 2A20 Approved [2]
Nodal marginal zone lymphoma 2A85.0 Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [2]
Recurrent adult burkitt lymphoma 2A85.6 Approved [2]
Small intestine lymphoma N.A. Approved [2]
Splenic marginal zone lymphoma N.A. Approved [2]
Systemic lupus erythematosus 4A40.0 Approved [2]
Systemic sclerosis 4A42 Approved [2]
Testicular lymphoma N.A. Approved [2]
Classic Hodgkin lymphoma N.A. Investigative [2]
Colon cancer 2B90.Z Investigative [2]
Gastric cancer 2B72 Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Fludarabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Fludarabine Interacts with 22 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Affects Expression [9]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [10]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [11]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Increases Expression [12]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [5]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [13]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [14]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [6]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [6]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Activity [15]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Increases Activity [15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [13]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [14]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Increases Activity [15]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [12]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [12]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [13]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [6]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [7]
Growth/differentiation factor 15 (GDF15) OTWQN50N GDF15_HUMAN Increases Expression [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 22 DOT(s)
Indication(s) of CATECHIN
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
CATECHIN Interacts with 9 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Carbonic anhydrase VI (CA-VI) TTCFSPE CAH6_HUMAN Inhibitor [4]
Carbonic anhydrase I (CA-I) TTHQPL7 CAH1_HUMAN Inhibitor [4]
Carbonic anhydrase XII (CA-XII) TTSYM0R CAH12_HUMAN Inhibitor [4]
Carbonic anhydrase II (CA-II) TTANPDJ CAH2_HUMAN Inhibitor [4]
Carbonic anhydrase XIV (CA-XIV) TTEYTKG CAH14_HUMAN Inhibitor [4]
Carbonic anhydrase (CA) TTUNARX NOUNIPROTAC Inhibitor [4]
Carbonic anhydrase IV (CA-IV) TTZHA0O CAH4_HUMAN Inhibitor [4]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Inhibitor [18]
Carbonic anhydrase IX (CA-IX) TT2LVK8 CAH9_HUMAN Inhibitor [4]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DTT(s)
CATECHIN Interacts with 75 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [19]
Interleukin-2 receptor subunit alpha (IL2RA) OT0MWCHG IL2RA_HUMAN Decreases Expression [16]
Ferritin heavy chain (FTH1) OT6IFS0O FRIH_HUMAN Increases Expression [16]
Thymidine kinase, cytosolic (TK1) OTY5JFM1 KITH_HUMAN Decreases Expression [16]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [16]
Nucleophosmin (NPM1) OTTBYYT0 NPM_HUMAN Decreases Expression [16]
Annexin A2 (ANXA2) OTFNS0CC ANXA2_HUMAN Increases Expression [16]
Tyrosine-protein kinase Lyn (LYN) OTP686K2 LYN_HUMAN Decreases Expression [16]
60 kDa heat shock protein, mitochondrial (HSPD1) OTTO1Y11 CH60_HUMAN Decreases Expression [16]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Expression [16]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [16]
Macrophage migration inhibitory factor (MIF) OTUCMVCX MIF_HUMAN Decreases Expression [16]
B-lymphocyte antigen CD19 (CD19) OTCPF9NF CD19_HUMAN Increases Expression [16]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [16]
Integrin alpha-L (ITGAL) OTCUQAIS ITAL_HUMAN Increases Expression [16]
CD9 antigen (CD9) OT2184XU CD9_HUMAN Increases Expression [16]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Expression [16]
Interleukin-32 (IL32) OT3FHZ81 IL32_HUMAN Decreases Expression [16]
Progranulin (GRN) OTXXSJ53 GRN_HUMAN Increases Expression [16]
Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) OTJ8UM8O TNR8_HUMAN Decreases Expression [16]
Homeobox protein Hox-D3 (HOXD3) OTBUZ35T HXD3_HUMAN Increases Expression [16]
Protein DEK (DEK) OTYCJ5H6 DEK_HUMAN Decreases Expression [16]
Transcription factor 7 (TCF7) OT1ID822 TCF7_HUMAN Increases Expression [16]
Signal transducer and activator of transcription 1-alpha/beta (STAT1) OTLMBUZ6 STAT1_HUMAN Decreases Expression [16]
Signal transducer and activator of transcription 6 (STAT6) OTCKMP49 STAT6_HUMAN Increases Expression [16]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Increases Expression [16]
Lys-63-specific deubiquitinase BRCC36 (BRCC3) OTK0ZN7Y BRCC3_HUMAN Decreases Expression [16]
Protein PRRC2A (PRRC2A) OTBX6FM5 PRC2A_HUMAN Increases Expression [16]
Fms-related tyrosine kinase 3 ligand (FLT3LG) OTU0YGC4 FLT3L_HUMAN Decreases Expression [16]
Host cell factor 1 (HCFC1) OT0UCK62 HCFC1_HUMAN Increases Expression [16]
Signal transducer and activator of transcription 5B (STAT5B) OTZVPEBT STA5B_HUMAN Increases Expression [16]
CCAAT/enhancer-binding protein gamma (CEBPG) OTGNAX3H CEBPG_HUMAN Increases Expression [16]
CD81 antigen (CD81) OTQFXNAZ CD81_HUMAN Increases Expression [16]
Protein BTG1 (BTG1) OTVJ2CDM BTG1_HUMAN Increases Expression [16]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Decreases Expression [16]
Rho GTPase-activating protein 4 (ARHGAP4) OTXV053R RHG04_HUMAN Decreases Expression [16]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Increases Expression [16]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Expression [16]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Increases Expression [16]
Interferon regulatory factor 4 (IRF4) OT1DHQ1P IRF4_HUMAN Decreases Expression [16]
Splicing factor 1 (SF1) OTLEDM2S SF01_HUMAN Decreases Expression [16]
Sodium-dependent phosphate transporter 1 (SLC20A1) OTC3D894 S20A1_HUMAN Increases Expression [16]
Polyribonucleotide 5'-hydroxyl-kinase Clp1 (CLP1) OTPY965Y CLP1_HUMAN Decreases Expression [16]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Activity [20]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Activity [20]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [21]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Increases Expression [22]
Tissue-type plasminogen activator (PLAT) OTQPDNAB TPA_HUMAN Increases Expression [22]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Decreases Expression [23]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [23]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [24]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Decreases Expression [23]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Increases Expression [25]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [26]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [23]
Retinoic acid receptor beta (RARB) OT367U3E RARB_HUMAN Decreases Metabolism [27]
Neutrophil cytosol factor 1 (NCF1) OTMHT3G6 NCF1_HUMAN Decreases Expression [28]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [29]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [30]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Activity [27]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [29]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [29]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [23]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Expression [23]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [23]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [30]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Decreases Expression [23]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [23]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Increases Phosphorylation [31]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [23]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [30]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [26]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Expression [32]
Sulfotransferase 1A1 (SULT1A1) OT0K7JIE ST1A1_HUMAN Increases Sulfation [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 75 DOT(s)

References

1 ClinicalTrials.gov (NCT03344705) Safety and Efficacy Evaluation of IM19 Cells
2 Fludarabine FDA Label
3 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: 4802).
4 Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
5 Role of histone deacetylase inhibitor-induced reactive oxygen species and DNA damage in LAQ-824/fludarabine antileukemic interactions. Mol Cancer Ther. 2008 Oct;7(10):3285-97. doi: 10.1158/1535-7163.MCT-08-0385.
6 9-beta-D-arabinofuranosyl-2-fluoroadenine inhibits expression of vascular endothelial growth factor through hypoxia-inducible factor-1 in human ovarian cancer cells. Mol Pharmacol. 2004 Jul;66(1):178-86. doi: 10.1124/mol.66.1.178.
7 MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood. 2006 May 15;107(10):4109-14. doi: 10.1182/blood-2005-08-3273. Epub 2006 Jan 26.
8 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
9 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
10 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
11 Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006 May 15;107(10):4122-9. doi: 10.1182/blood-2005-11-4465. Epub 2006 Jan 26.
12 Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide. PLoS One. 2014 Jun 23;9(6):e99993. doi: 10.1371/journal.pone.0099993. eCollection 2014.
13 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
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 The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Res. 2004 Apr 1;64(7):2590-600. doi: 10.1158/0008-5472.can-03-2631.
16 Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.
17 Phloretin exhibits potential food-drug interactions by inhibiting human UDP-glucuronosyltransferases in vitro. Toxicol In Vitro. 2022 Oct;84:105447. doi: 10.1016/j.tiv.2022.105447. Epub 2022 Jul 19.
18 Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure-activity relationship study. J Nat Prod. 2004 Nov;67(11):1777-82.
19 Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship. Jpn J Cancer Res. 2000 Jul;91(7):686-91.
20 Green tea catechins alone or in combination alter functional parameters of human neutrophils via suppressing the activation of TLR-4/NFB p65 signal pathway. Toxicol In Vitro. 2015 Oct;29(7):1766-78.
21 Stable cellular models of nuclear receptor PXR for high-throughput evaluation of small molecules. Toxicol In Vitro. 2018 Oct;52:222-234.
22 Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells. Alcohol Clin Exp Res. 2001 Feb;25(2):155-62.
23 Cytotoxicity and apoptosis induction in human breast adenocarcinoma MCF-7 cells by (+)-cyanidan-3-ol. Exp Toxicol Pathol. 2013 Nov;65(7-8):1091-100. doi: 10.1016/j.etp.2013.04.005. Epub 2013 May 21.
24 Polyphenols downregulate PAI-1 gene expression in cultured human coronary artery endothelial cells: molecular contributor to cardiovascular protection. Thromb Res. 2007;121(1):59-65. doi: 10.1016/j.thromres.2007.02.001. Epub 2007 Mar 26.
25 (-)-Epicatechin rescues the As(2) O(3) -induced HERG K(+) channel deficiency possibly through upregulating transcription factor SP1 expression. J Biochem Mol Toxicol. 2017 Nov;31(11). doi: 10.1002/jbt.21966. Epub 2017 Aug 2.
26 Flavonoids protect human retinal pigment epithelial cells from oxidative-stress-induced death. Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3164-77. doi: 10.1167/iovs.04-1369.
27 Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids. Mol Pharmacol. 2005 Oct;68(4):1018-30. doi: 10.1124/mol.104.008367. Epub 2005 Jul 21.
28 Effects of red grape juice polyphenols in NADPH oxidase subunit expression in human neutrophils and mononuclear blood cells. Br J Nutr. 2009 Oct;102(8):1125-35. doi: 10.1017/S0007114509382148. Epub 2009 May 19.
29 The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth. Free Radic Biol Med. 2006 Jan 15;40(2):323-34. doi: 10.1016/j.freeradbiomed.2005.08.031. Epub 2005 Oct 11.
30 Role of fatty acid chain length on the induction of apoptosis by newly synthesized catechin derivatives. Chem Biol Interact. 2010 May 14;185(3):182-8. doi: 10.1016/j.cbi.2010.02.045. Epub 2010 Mar 4.
31 Monomeric and oligomeric flavanols are agonists of membrane androgen receptors. Exp Cell Res. 2005 Oct 1;309(2):329-39. doi: 10.1016/j.yexcr.2005.06.011.
32 Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate. Toxicol Sci. 2007 Apr;96(2):227-36. doi: 10.1093/toxsci/kfl147. Epub 2006 Oct 31.
33 Variable sulfation of dietary polyphenols by recombinant human sulfotransferase (SULT) 1A1 genetic variants and SULT1E1. Drug Metab Dispos. 2007 May;35(5):740-6. doi: 10.1124/dmd.106.013987. Epub 2007 Feb 9.