Details of the Drug Combination

General Information of Drug Combination (ID: DCCY955)

Drug Combination Name
Selumetinib Capecitabine
Indication
Disease Entry Status REF
Non-Metastatic Adenocarcinoma of the Rectum Phase 1 [1]
Component Drugs Selumetinib   DMC7W6R Capecitabine   DMTS85L
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 Selumetinib
Disease Entry ICD 11 Status REF
Neurofibromatosis type 1 LD2D.10 Approved [2]
Melanoma 2C30 Phase 3 [3]
Thyroid cancer 2D10 Phase 3 [4]
Non-small-cell lung cancer 2C25.Y Phase 2 [5]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [6]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [6]
Solid tumour/cancer 2A00-2F9Z Investigative [7]
Selumetinib Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [10]
ERK activator kinase 1 (MEK1) TTIDAPM MP2K1_HUMAN Inhibitor [4]
ERK activator kinase 2 (MEK2) TTTW2NY MP2K2_HUMAN Inhibitor [4]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [6]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Selumetinib Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [11]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Decreases Phosphorylation [12]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Activity [12]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [12]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Activity [12]
Cyclic AMP-responsive element-binding protein 1 (CREB1) OT1MDLA1 CREB1_HUMAN Decreases Phosphorylation [12]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [13]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [13]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DOT(s)
Indication(s) of Capecitabine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [8]
Colon adenocarcinoma N.A. Approved [8]
Colorectal cancer 2B91.Z Approved [9]
Metastasis from malignant tumor of colon N.A. Approved [8]
Rectal adenocarcinoma 2B92 Approved [8]
Breast cancer 2C60-2C65 Phase 3 [9]
Colon cancer 2B90.Z Investigative [8]
Gastric cancer 2B72 Investigative [8]
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 [16]
------------------------------------------------------------------------------------
Capecitabine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytidine aminohydrolase (CDA) DEKEDRC CDD_HUMAN Metabolism [17]
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [18]
------------------------------------------------------------------------------------
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 [19]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [20]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [20]
C-C motif chemokine 21 (CCL21) OT7DOXEM CCL21_HUMAN Decreases Expression [14]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Decreases Expression [14]
Aquaporin-8 (AQP8) OT99JKME AQP8_HUMAN Increases Expression [14]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [14]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Decreases Expression [14]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [21]
B-lymphocyte antigen CD20 (MS4A1) OTZTVUBX CD20_HUMAN Decreases Expression [14]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Decreases Expression [14]
40-kDa huntingtin-associated protein (F8A1) OTXTQ59R HAP40_HUMAN Decreases Expression [14]
Chloride anion exchanger (SLC26A3) OTBNK2U2 S26A3_HUMAN Increases Expression [14]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Decreases Expression [14]
Potassium-transporting ATPase alpha chain 2 (ATP12A) OTSQSKEK AT12A_HUMAN Increases Expression [14]
Serine/threonine-protein kinase SIK1 (SIK1) OT6FCHME SIK1_HUMAN Decreases Expression [14]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Decreases Expression [14]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Decreases Expression [14]
Paired box protein Pax-5 (PAX5) OTYBJJWX PAX5_HUMAN Decreases Expression [14]
Endoplasmic reticulum aminopeptidase 2 (ERAP2) OTEMENYF ERAP2_HUMAN Decreases Expression [14]
Fc receptor-like A (FCRLA) OT6MK4M1 FCRLA_HUMAN Decreases Expression [14]
Leucine-rich repeat-containing protein 15 (LRRC15) OTX7JL8H LRC15_HUMAN Decreases Expression [14]
C-C motif chemokine 19 (CCL19) OTQ2UJMH CCL19_HUMAN Decreases Expression [14]
E3 ubiquitin-protein ligase TRIM31 (TRIM31) OT7VW6RP TRI31_HUMAN Increases Expression [14]
Interleukin-1 receptor type 2 (IL1R2) OT0G7E35 IL1R2_HUMAN Increases Response To Substance [15]
Interleukin-17 receptor B (IL17RB) OT0KDNSF I17RB_HUMAN Increases Response To Substance [15]
Glycogen phosphorylase, brain form (PYGB) OT2ZTJT0 PYGB_HUMAN Increases Response To Substance [15]
Calcium and integrin-binding protein 1 (CIB1) OT4BVCRU CIB1_HUMAN Increases Response To Substance [15]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Increases Response To Substance [15]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB) OT6RMDCE KAPCB_HUMAN Decreases Response To Substance [15]
Claudin-3 (CLDN3) OT71MN9S CLD3_HUMAN Increases Response To Substance [15]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Decreases Response To Substance [15]
Protein flightless-1 homolog (FLII) OT7G9JG6 FLII_HUMAN Decreases Response To Substance [15]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Response To Substance [15]
Ras-related protein R-Ras2 (RRAS2) OT83NCEB RRAS2_HUMAN Decreases Response To Substance [15]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Response To Substance [15]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Response To Substance [22]
Ras-related protein Rab-40B (RAB40B) OTCA9ZF5 RB40B_HUMAN Increases Response To Substance [15]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Response To Substance [15]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7) OTDNTHNR ABCB7_HUMAN Decreases Response To Substance [15]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) OTESFZSO PTN13_HUMAN Decreases Response To Substance [15]
ADP-ribosylation factor-like protein 4D (ARL4D) OTG5I3KU ARL4D_HUMAN Decreases Response To Substance [15]
Double-strand break repair protein MRE11 (MRE11) OTGU8TZM MRE11_HUMAN Decreases Response To Substance [15]
Inorganic pyrophosphatase (PPA1) OTHZK1QB IPYR_HUMAN Increases Response To Substance [15]
Polycystin-2 (PKD2) OTIXBU8H PKD2_HUMAN Decreases Response To Substance [15]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [15]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Increases Response To Substance [15]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Increases Response To Substance [15]
Plakophilin-2 (PKP2) OTJOVF68 PKP2_HUMAN Increases Response To Substance [15]
Transcriptional enhancer factor TEF-1 (TEAD1) OTK6971C TEAD1_HUMAN Decreases Response To Substance [15]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Response To Substance [15]
Myelin regulatory factor (MYRF) OTKF6AEB MYRF_HUMAN Increases Response To Substance [15]
Galectin-4 (LGALS4) OTKQCG0H LEG4_HUMAN Increases Response To Substance [15]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Response To Substance [15]
Hepatoma-derived growth factor-related protein 3 (HDGFL3) OTNN7WYH HDGR3_HUMAN Decreases Response To Substance [15]
E3 ubiquitin-protein ligase TRIM15 (TRIM15) OTNYAKP6 TRI15_HUMAN Increases Response To Substance [15]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Decreases Response To Substance [15]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Increases Response To Substance [15]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Response To Substance [15]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Decreases Response To Substance [15]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Response To Substance [15]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1) OTVKRET0 THIK_HUMAN Increases Response To Substance [15]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Increases Response To Substance [15]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Response To Substance [15]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Increases Response To Substance [15]
------------------------------------------------------------------------------------
⏷ Show the Full List of 65 DOT(s)

References

1 ClinicalTrials.gov (NCT01134601) A Phase I Study of AZD6244 in Combination With Capecitabine and Radiotherapy in Locally Advanced Adenocarcinoma of the Rectum
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 ClinicalTrials.gov (NCT01933932) Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 5665).
6 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
7 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. (Target id: 1479).
8 Capecitabine FDA Label
9 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).
10 Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
11 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
12 Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway. Chem Biol Interact. 2020 Jan 5;315:108910. doi: 10.1016/j.cbi.2019.108910. Epub 2019 Nov 29.
13 The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. Br J Cancer. 2012 Apr 10;106(8):1386-94. doi: 10.1038/bjc.2012.70. Epub 2012 Mar 13.
14 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.
15 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.
16 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.
17 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.
18 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.
19 DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
20 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.
21 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.
22 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.