Drug Information

Drug (ID: DG00003) and It's Reported Resistant Information

• Name: Capecitabine
• Synonyms: Capecitabin; Capecitabina; Capecitabinum; Capecitibine; Capiibine; Caxeta; Xabine; Xeloda; Capecitabine [USAN]; R340;R-340; RG-340; Ro 09-1978; Xeloda (TN); Ro 09-1978/000; Ro-09-1978; Xeloda, Captabin, Capecitabine; Capecitabine (JAN/USAN/INN); Ro-09-1978/000; N(4)-Pentyloxycarbonyl-5'-deoxy-5-fluorocytidine; Pentyl 1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate; Pentyl [1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate; Carbamic acid, (1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-, pentyl ester; Pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate; (1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl ester; 5'-Deoxy-5-fluoro-N-((pentyloxy)carbonyl)cytidine; 5'-deoxy-5-fluoro-N-[(pentyloxy)carbonyl]cytidine; Capecitabine (Fluoropyrimidine)
• Indication:
  In total 2 Indication(s)
  Colorectal cancer [ICD-11: 2B91]; Approved; [1]
  Breast cancer [ICD-11: 2C60]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Colon cancer [ICD-11: 2B90]; [1]
• Target: Candida Thymidylate synthase (Candi TMP1); TYSY_CANAL; [1]
• Formula: C15H22FN3O6
• IsoSMILES: CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@H]2[C@@H]([C@@H]([C@H](O2)C)O)O
• InChI: 1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1
• InChIKey: GAGWJHPBXLXJQN-UORFTKCHSA-N
• PubChem CID: 60953
• ChEBI ID: CHEBI:31348
• TTD Drug ID: D00HCQ
• VARIDT ID: DR00380
• INTEDE ID: DR0266
• DrugBank ID: DB01101

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Colon cancer [ICD-11: 2B90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-296 [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Response evaluation criteria in solid tumors assay
• Mechanism Description: The patients with decrease in miR-296 at 4 weeks may reflect a more aggressive tumor phenotype with increased metastasis and tumor cell invasiveness. The loss of miR-296 may be one of the mechanisms for primary resistance of colorectal cancer to chemotherapy.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Growth arrest-specific protein 6 (GAS6) [2]

• Molecule Alteration: Splicing mutation; Splicing
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AXLK signaling pathway; Activation; hsa01521
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Circulating-free DNA assay; Whole exome sequencing assay
• Mechanism Description: Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.

Key Molecule: Tumor protein 63 (TP63) [2]

• Molecule Alteration: Missense mutation; p.S551G
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AXLK signaling pathway; Activation; hsa01521
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Circulating-free DNA assay; Whole exome sequencing assay
• Mechanism Description: Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.

Key Molecule: Tumor protein 63 (TP63) [2]

• Molecule Alteration: Missense mutation; p.S551G
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Circulating-free DNA assay; Whole exome sequencing assay
• Mechanism Description: Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.

References

• Ref 1: Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int J Colorectal Dis. 2013 Jun;28(6):887. doi: 10.1007/s00384-012-1560-1. Epub 2012 Aug 15.
• Ref 2: Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.