The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine

Shimma, Nobuo; Umeda, Isao; Arasaki, Motohiro; Murasaki, Chikako; Masubuchi, Kazunao; Kohchi, Yasunori; Miwa, Masanori; Ura, Masako; Sawada, Noriaki; Tahara, Hitoshi; Kuruma, Isamu; Horii, Ikuo; Ishitsuka, Hideo

doi:10.1016/s0968-0896(00)00087-0

Cited by 124 publications

(92 citation statements)

References 16 publications

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“…The effective concentration necessary for 50% growth inhibition (EC 50 ) of each transfectant in a 3-day cytotoxicity assay was determined and is presented in Table 1. Comparison of the EC 50 values for HEK-vector and HEK-MRP5 indicated that HEK-MRP5 is f9-fold resistant to both 6-TG and 5-FU and f2-fold to 5V -deoxy-5V -fluorouridine, which is subsequently metabolized to 5-FU in tumor cells (22). These MRP5-transfected HEK cells were also 4-to 8-fold resistant to methotrexate and pemetrexed, approximately 3-fold resistant to the platinum-containing anticancer agents cisplatin and oxaliplatin, and 2-fold resistant to doxorubicin.…”

Section: Resultsmentioning

confidence: 99%

The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

Pratt

Shepard

Kandasamy³

et al. 2005

Molecular Cancer Therapeutics

211

175

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Abstract5V -Fluorouracil (5-FU), used in the treatment of colon and breast cancers, is converted intracellularly to 5V -fluoro-2V -deoxyuridine (5-FUdR) by thymidine phosphorylase and is subsequently phosphorylated by thymidine kinase to 5V -fluoro-2V -dUMP (5-FdUMP). This active metabolite, along with the reduced folate cofactor, 5,10-methylenetetrahydrofolate, forms a stable inhibitory complex with thymidylate synthase that blocks cellular growth. The present study shows that the ATP-dependent multidrug resistance protein-5 (MRP5, ABCC5) confers resistance to 5-FU by transporting the monophosphate metabolites. MRP5-and vector-transfected human embryonic kidney (HEK) cells were employed in these studies. In 3-day cytotoxicity assays, MRP5-transfected cells were f9-fold resistant to 5-FU and 6-thioguanine. Studies with inside-out membrane vesicles prepared from transfected cells showed that MRP5 mediates ATP-dependent transport of 5 Mmol/L

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Section: Resultsmentioning

confidence: 99%

The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

Pratt

Shepard

Kandasamy³

et al. 2005

Molecular Cancer Therapeutics

211

175

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“…Several studies have examined the use of new oral chemotherapeutic agents in the CRT protocol for treatment of rectal cancer with many biologic and clinical advantages including mimicking protracted infusion of 5-FU. [7][8][9][10] In a prospective phase 2 trial of preoperative CRT with capecitabine, we reported encouraging rates of tumor downstaging, sphincter preservation, and low toxicity. 11 With such encouraging outcomes, we designed a prospective, single institution phase 3 trial that compared preoperative CRT and postoperative CRT in survival, local control, sphincter preservation, and treatmentrelated toxicity for treatment of locally advanced rectal cancer.…”

mentioning

confidence: 95%

Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer

Park

Yoon

et al. 2011

Cancer

137

111

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BACKGROUND: Although many trials have shown the efficacy of preoperative chemoradiotherapy (CRT) or postoperative CRT compared with surgery alone, the optimal sequence of radiotherapy and surgery is unclear. The authors reported the final results of this single institution prospective randomized phase 3 trial comparing preoperative CRT with postoperative CRT using capecitabine in survival, local control, sphincter preservation, and toxicity for the treatment of locally advanced rectal cancer. METHODS: Patients with locally advanced rectal cancer (cT3, potentially resectable cT4 or Nþ) were randomly assigned to receive preoperative or postoperative CRT. CRT consisted of 50 Gy/ 25 fractions and concurrent capecitabine (1,650 mg/m

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“…Because intracellular MTA is metabolized rapidly by MTA phosphorylase (MTAP) in mammalian cells, adenine which is known to be a potent MTAP inhibitor, 26,27 was added to the reaction mixture to block endogenous MTAP in this experiment. Etheno-derivatized MTA and adenine were detected at 25 and 22 min, respectively, as shown in the HPLC chromatograms for Spdsyn activity assay in supernatant protein of HepG2 cells (Figs.…”

Section: Measurement Of Apt Activity In Hepg2 Cellsmentioning

confidence: 99%

Determination of Cellular Aminopropyltransferase Activity Using Precolumn Fluorescent Etheno-Derivatization with High-Performance Liquid Chromatography

et al. 2012

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The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine

Cited by 124 publications

References 16 publications

The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer

Determination of Cellular Aminopropyltransferase Activity Using Precolumn Fluorescent Etheno-Derivatization with High-Performance Liquid Chromatography

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