Details of the Drug Combination

General Information of Drug Combination (ID: DCBSGJK)

Drug Combination Name
CB-839 Capecitabine
Indication
Disease Entry Status REF
Colorectal Cancer Phase 1 [1]
Component Drugs CB-839   DM094UH Capecitabine   DMTS85L
N.A. 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 CB-839
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Renal cell carcinoma 2C90 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
leukaemia 2A60-2B33 Phase 1 [3]
CB-839 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glutaminase (GLS) TTCW0KX GLSK_HUMAN; GLSL_HUMAN Modulator [6]
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CB-839 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Decreases Activity [7]
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Indication(s) of Capecitabine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [4]
Colon adenocarcinoma N.A. Approved [4]
Colorectal cancer 2B91.Z Approved [5]
Metastasis from malignant tumor of colon N.A. Approved [4]
Rectal adenocarcinoma 2B92 Approved [4]
Breast cancer 2C60-2C65 Phase 3 [5]
Colon cancer 2B90.Z Investigative [4]
Gastric cancer 2B72 Investigative [4]
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 [10]
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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 [11]
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [12]
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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 [13]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [14]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [14]
C-C motif chemokine 21 (CCL21) OT7DOXEM CCL21_HUMAN Decreases Expression [8]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Decreases Expression [8]
Aquaporin-8 (AQP8) OT99JKME AQP8_HUMAN Increases Expression [8]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [8]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Decreases Expression [8]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [15]
B-lymphocyte antigen CD20 (MS4A1) OTZTVUBX CD20_HUMAN Decreases Expression [8]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Decreases Expression [8]
40-kDa huntingtin-associated protein (F8A1) OTXTQ59R HAP40_HUMAN Decreases Expression [8]
Chloride anion exchanger (SLC26A3) OTBNK2U2 S26A3_HUMAN Increases Expression [8]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Decreases Expression [8]
Potassium-transporting ATPase alpha chain 2 (ATP12A) OTSQSKEK AT12A_HUMAN Increases Expression [8]
Serine/threonine-protein kinase SIK1 (SIK1) OT6FCHME SIK1_HUMAN Decreases Expression [8]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Decreases Expression [8]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Decreases Expression [8]
Paired box protein Pax-5 (PAX5) OTYBJJWX PAX5_HUMAN Decreases Expression [8]
Endoplasmic reticulum aminopeptidase 2 (ERAP2) OTEMENYF ERAP2_HUMAN Decreases Expression [8]
Fc receptor-like A (FCRLA) OT6MK4M1 FCRLA_HUMAN Decreases Expression [8]
Leucine-rich repeat-containing protein 15 (LRRC15) OTX7JL8H LRC15_HUMAN Decreases Expression [8]
C-C motif chemokine 19 (CCL19) OTQ2UJMH CCL19_HUMAN Decreases Expression [8]
E3 ubiquitin-protein ligase TRIM31 (TRIM31) OT7VW6RP TRI31_HUMAN Increases Expression [8]
Interleukin-1 receptor type 2 (IL1R2) OT0G7E35 IL1R2_HUMAN Increases Response To Substance [9]
Interleukin-17 receptor B (IL17RB) OT0KDNSF I17RB_HUMAN Increases Response To Substance [9]
Glycogen phosphorylase, brain form (PYGB) OT2ZTJT0 PYGB_HUMAN Increases Response To Substance [9]
Calcium and integrin-binding protein 1 (CIB1) OT4BVCRU CIB1_HUMAN Increases Response To Substance [9]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Increases Response To Substance [9]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB) OT6RMDCE KAPCB_HUMAN Decreases Response To Substance [9]
Claudin-3 (CLDN3) OT71MN9S CLD3_HUMAN Increases Response To Substance [9]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Decreases Response To Substance [9]
Protein flightless-1 homolog (FLII) OT7G9JG6 FLII_HUMAN Decreases Response To Substance [9]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Response To Substance [9]
Ras-related protein R-Ras2 (RRAS2) OT83NCEB RRAS2_HUMAN Decreases Response To Substance [9]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Response To Substance [9]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Response To Substance [16]
Ras-related protein Rab-40B (RAB40B) OTCA9ZF5 RB40B_HUMAN Increases Response To Substance [9]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Response To Substance [9]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7) OTDNTHNR ABCB7_HUMAN Decreases Response To Substance [9]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) OTESFZSO PTN13_HUMAN Decreases Response To Substance [9]
ADP-ribosylation factor-like protein 4D (ARL4D) OTG5I3KU ARL4D_HUMAN Decreases Response To Substance [9]
Double-strand break repair protein MRE11 (MRE11) OTGU8TZM MRE11_HUMAN Decreases Response To Substance [9]
Inorganic pyrophosphatase (PPA1) OTHZK1QB IPYR_HUMAN Increases Response To Substance [9]
Polycystin-2 (PKD2) OTIXBU8H PKD2_HUMAN Decreases Response To Substance [9]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [9]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Increases Response To Substance [9]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Increases Response To Substance [9]
Plakophilin-2 (PKP2) OTJOVF68 PKP2_HUMAN Increases Response To Substance [9]
Transcriptional enhancer factor TEF-1 (TEAD1) OTK6971C TEAD1_HUMAN Decreases Response To Substance [9]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Response To Substance [9]
Myelin regulatory factor (MYRF) OTKF6AEB MYRF_HUMAN Increases Response To Substance [9]
Galectin-4 (LGALS4) OTKQCG0H LEG4_HUMAN Increases Response To Substance [9]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Response To Substance [9]
Hepatoma-derived growth factor-related protein 3 (HDGFL3) OTNN7WYH HDGR3_HUMAN Decreases Response To Substance [9]
E3 ubiquitin-protein ligase TRIM15 (TRIM15) OTNYAKP6 TRI15_HUMAN Increases Response To Substance [9]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Decreases Response To Substance [9]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Increases Response To Substance [9]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Response To Substance [9]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Decreases Response To Substance [9]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Response To Substance [9]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1) OTVKRET0 THIK_HUMAN Increases Response To Substance [9]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Increases Response To Substance [9]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Response To Substance [9]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Increases Response To Substance [9]
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⏷ Show the Full List of 65 DOT(s)

References

1 ClinicalTrials.gov (NCT02861300) CB-839 + Capecitabine in Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT02071862) Study of the Glutaminase Inhibitor CB-839 in Solid Tumors. U.S. National Institutes of Health.
4 Capecitabine 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: 6799).
6 Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901.
7 Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells. J Biol Chem. 2019 Jun 14;294(24):9342-9357.
8 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.
9 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.
10 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.
11 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.
12 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.
13 DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
14 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.
15 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.
16 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.