Details of the Drug Combination

General Information of Drug Combination (ID: DC7K2S6)

Drug Combination Name
Capecitabine Hydroxychloroquine
Indication
Disease Entry Status REF
Pancreatic Cancer Phase 1 [1]
Component Drugs Capecitabine   DMTS85L Hydroxychloroquine   DMSIVND
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 Capecitabine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Colon adenocarcinoma N.A. Approved [2]
Colorectal cancer 2B91.Z Approved [3]
Metastasis from malignant tumor of colon N.A. Approved [2]
Rectal adenocarcinoma 2B92 Approved [2]
Breast cancer 2C60-2C65 Phase 3 [3]
Colon cancer 2B90.Z Investigative [2]
Gastric cancer 2B72 Investigative [2]
Capecitabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [9]
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Capecitabine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytidine aminohydrolase (CDA) DEKEDRC CDD_HUMAN Metabolism [10]
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [11]
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Capecitabine Interacts with 65 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydropyrimidine dehydrogenase (DPYD) OTWRF2NR DPYD_HUMAN Increases Expression [12]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [13]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [13]
C-C motif chemokine 21 (CCL21) OT7DOXEM CCL21_HUMAN Decreases Expression [7]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Decreases Expression [7]
Aquaporin-8 (AQP8) OT99JKME AQP8_HUMAN Increases Expression [7]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [7]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Decreases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [14]
B-lymphocyte antigen CD20 (MS4A1) OTZTVUBX CD20_HUMAN Decreases Expression [7]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Decreases Expression [7]
40-kDa huntingtin-associated protein (F8A1) OTXTQ59R HAP40_HUMAN Decreases Expression [7]
Chloride anion exchanger (SLC26A3) OTBNK2U2 S26A3_HUMAN Increases Expression [7]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Decreases Expression [7]
Potassium-transporting ATPase alpha chain 2 (ATP12A) OTSQSKEK AT12A_HUMAN Increases Expression [7]
Serine/threonine-protein kinase SIK1 (SIK1) OT6FCHME SIK1_HUMAN Decreases Expression [7]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Decreases Expression [7]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Decreases Expression [7]
Paired box protein Pax-5 (PAX5) OTYBJJWX PAX5_HUMAN Decreases Expression [7]
Endoplasmic reticulum aminopeptidase 2 (ERAP2) OTEMENYF ERAP2_HUMAN Decreases Expression [7]
Fc receptor-like A (FCRLA) OT6MK4M1 FCRLA_HUMAN Decreases Expression [7]
Leucine-rich repeat-containing protein 15 (LRRC15) OTX7JL8H LRC15_HUMAN Decreases Expression [7]
C-C motif chemokine 19 (CCL19) OTQ2UJMH CCL19_HUMAN Decreases Expression [7]
E3 ubiquitin-protein ligase TRIM31 (TRIM31) OT7VW6RP TRI31_HUMAN Increases Expression [7]
Interleukin-1 receptor type 2 (IL1R2) OT0G7E35 IL1R2_HUMAN Increases Response To Substance [8]
Interleukin-17 receptor B (IL17RB) OT0KDNSF I17RB_HUMAN Increases Response To Substance [8]
Glycogen phosphorylase, brain form (PYGB) OT2ZTJT0 PYGB_HUMAN Increases Response To Substance [8]
Calcium and integrin-binding protein 1 (CIB1) OT4BVCRU CIB1_HUMAN Increases Response To Substance [8]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Increases Response To Substance [8]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB) OT6RMDCE KAPCB_HUMAN Decreases Response To Substance [8]
Claudin-3 (CLDN3) OT71MN9S CLD3_HUMAN Increases Response To Substance [8]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Decreases Response To Substance [8]
Protein flightless-1 homolog (FLII) OT7G9JG6 FLII_HUMAN Decreases Response To Substance [8]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Response To Substance [8]
Ras-related protein R-Ras2 (RRAS2) OT83NCEB RRAS2_HUMAN Decreases Response To Substance [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Response To Substance [8]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Response To Substance [15]
Ras-related protein Rab-40B (RAB40B) OTCA9ZF5 RB40B_HUMAN Increases Response To Substance [8]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Response To Substance [8]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7) OTDNTHNR ABCB7_HUMAN Decreases Response To Substance [8]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) OTESFZSO PTN13_HUMAN Decreases Response To Substance [8]
ADP-ribosylation factor-like protein 4D (ARL4D) OTG5I3KU ARL4D_HUMAN Decreases Response To Substance [8]
Double-strand break repair protein MRE11 (MRE11) OTGU8TZM MRE11_HUMAN Decreases Response To Substance [8]
Inorganic pyrophosphatase (PPA1) OTHZK1QB IPYR_HUMAN Increases Response To Substance [8]
Polycystin-2 (PKD2) OTIXBU8H PKD2_HUMAN Decreases Response To Substance [8]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [8]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Increases Response To Substance [8]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Increases Response To Substance [8]
Plakophilin-2 (PKP2) OTJOVF68 PKP2_HUMAN Increases Response To Substance [8]
Transcriptional enhancer factor TEF-1 (TEAD1) OTK6971C TEAD1_HUMAN Decreases Response To Substance [8]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Response To Substance [8]
Myelin regulatory factor (MYRF) OTKF6AEB MYRF_HUMAN Increases Response To Substance [8]
Galectin-4 (LGALS4) OTKQCG0H LEG4_HUMAN Increases Response To Substance [8]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Response To Substance [8]
Hepatoma-derived growth factor-related protein 3 (HDGFL3) OTNN7WYH HDGR3_HUMAN Decreases Response To Substance [8]
E3 ubiquitin-protein ligase TRIM15 (TRIM15) OTNYAKP6 TRI15_HUMAN Increases Response To Substance [8]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Decreases Response To Substance [8]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Increases Response To Substance [8]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Response To Substance [8]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Decreases Response To Substance [8]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Response To Substance [8]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1) OTVKRET0 THIK_HUMAN Increases Response To Substance [8]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Increases Response To Substance [8]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Response To Substance [8]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Increases Response To Substance [8]
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⏷ Show the Full List of 65 DOT(s)
Indication(s) of Hydroxychloroquine
Disease Entry ICD 11 Status REF
Chronic renal failure GB61.Z Approved [4]
Malaria 1F40-1F45 Approved [5]
Plasmodium falciparum malaria 1F40 Approved [4]
Plasmodium malariae malaria N.A. Approved [4]
Plasmodium ovale malaria N.A. Approved [4]
Systemic lupus erythematosus 4A40.0 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
Colon cancer 2B90.Z Investigative [4]
Hydroxychloroquine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R) TTD16BI N.A. Inhibitor [16]
HUMAN glycosylation of host receptor (GHR) TTZGK1R N.A. Inhibitor [16]
Toll-like receptor 7 (TLR7) TTRJ1K4 TLR7_HUMAN Antagonist [17]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway) TT3A1EZ N.A. Inhibitor [18]
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Hydroxychloroquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [19]
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Hydroxychloroquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [20]
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Hydroxychloroquine Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [21]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) OTPGHZB9 IFIT3_HUMAN Increases Expression [22]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [23]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [22]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) OT4TMERS NFAC1_HUMAN Affects Expression [24]
Claudin-1 (CLDN1) OT27KV99 CLD1_HUMAN Increases Expression [25]
Interferon beta (IFNB1) OTYQGUB5 IFNB_HUMAN Increases Expression [22]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Expression [22]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Affects Expression [26]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Affects Expression [26]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [22]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Affects Localization [27]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [28]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [29]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [29]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Degradation [22]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [23]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [22]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Activity [27]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Increases Expression [22]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) OTK5T6HZ NFAC2_HUMAN Affects Localization [24]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [30]
Interferon regulatory factor 3 (IRF3) OT81U8ME IRF3_HUMAN Increases Phosphorylation [22]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Increases Expression [25]
Mitochondrial antiviral-signaling protein (MAVS) OTTQ0J64 MAVS_HUMAN Increases Expression [22]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2) OTCA9WCM RSAD2_HUMAN Increases Expression [22]
Interferon-induced helicase C domain-containing protein 1 (IFIH1) OTZA2AHA IFIH1_HUMAN Increases Expression [22]
Toll-like receptor 9 (TLR9) OTFZ45HX TLR9_HUMAN Decreases Expression [31]
7-dehydrocholesterol reductase (DHCR7) OTLILBUI DHCR7_HUMAN Affects Expression [26]
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⏷ Show the Full List of 30 DOT(s)

References

1 ClinicalTrials.gov (NCT01494155) Short Course Radiation Therapy With Proton or Photon Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer
2 Capecitabine 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: 6799).
4 Hydroxychloroquine FDA Label
5 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: 7198).
6 ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
7 Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
8 Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
9 UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
10 Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805.
11 Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
12 DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
13 Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. Biomed Pharmacother. 2007 Oct;61(9):596-600.
14 P38 MAPK, NF-B, and JAK-STAT3 Signaling Pathways Involved in Capecitabine-Induced Hand-Foot Syndrome via Interleukin 6 or Interleukin 8 Abnormal Expression. Chem Res Toxicol. 2022 Mar 21;35(3):422-430. doi: 10.1021/acs.chemrestox.1c00317. Epub 2022 Feb 11.
15 A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Curr Drug Metab. 2008 May;9(4):336-43. doi: 10.2174/138920008784220646.
16 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
17 TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
18 Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
19 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
20 Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
21 Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
22 Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
23 Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
24 Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
25 Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
26 Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
27 Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
28 Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
29 Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
30 d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
31 Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.