FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W580688262> ?p ?o ?g. }

• W580688262 abstract "Over 65,000 people acquired renal cell carcinoma (RCC) and over 13,500 people died from the disease in the United States in 2012. The median survival for persons with metastatic disease is 13 months. Recent research has identified new targets for this disease and new targeted therapies have been developed. Despite this, the overall survival remains poor, and there remains a need for new therapies for RCC. Benzaldehyde dimethane sulfonate (BEN, DMS612) is a bifunctional alkylating agent with activity against renal cell carcinoma. The goal of the research conducted was to evaluate the preclinical and clinical pharmacology of BEN. Benzaldehyde dimethane sulfonate is stable in plasma but is metabolized in blood by aldehyde dehydrogenase into an acid that decomposes in aqueous and biological matrices. Furthermore, the acid product decomposes into 6 different species of which none are as active as BEN in the renal carcinoma cells that we have tested. We also found that BEN had greater activity in renal carcinoma cell lines that expressed higher levels of aldehyde dehydrogenase. This led us to believe that BEN acts as a pro-drug with its main carboxylic acid metabolite exerting the activity against renal carcinoma cell lines. We determined that BEN is rapidly metabolized in mice and that the pretreatment of mice with the aldehyde dehydrogenase inhibitor disulfiram greatly increases the exposure to BEN. Furthermore the carboxylic decomposition products that were detected in vitro were also found in the mice along with corresponding glucuronides. Also, we found that BEN when administered to patients is very rapidly metabolized and the same glucuronides generated in mice were also detected in humans. The maximum tolerated dose in a phase I clinical trial in humans was 9.0 mg/m2. The dose limiting toxicity was neutropenia. The information generated in this dissertation will be instrumental in the future clinical development of BEN." @default.
• W580688262 created "2016-06-24" @default.
• W580688262 creator A5077511890 @default.
• W580688262 date "2014-04-18" @default.
• W580688262 modified "2023-09-24" @default.
• W580688262 title "THE PRECLINICAL AND CLINICAL PHARMACOLOGY OF BENZALDEHYDE DIMETHANE SULFONATE (BEN) FOR THE TREATMENT OF RENAL CELL CARCINOMA" @default.
• W580688262 cites W108422045 @default.
• W580688262 cites W1487835988 @default.
• W580688262 cites W1495710350 @default.
• W580688262 cites W1524246713 @default.
• W580688262 cites W1545715398 @default.
• W580688262 cites W1559764573 @default.
• W580688262 cites W1592698345 @default.
• W580688262 cites W172596912 @default.
• W580688262 cites W1754555893 @default.
• W580688262 cites W1968004589 @default.
• W580688262 cites W1968332094 @default.
• W580688262 cites W1974466912 @default.
• W580688262 cites W1976204353 @default.
• W580688262 cites W1976949137 @default.
• W580688262 cites W1977541322 @default.
• W580688262 cites W1979814852 @default.
• W580688262 cites W1980339772 @default.
• W580688262 cites W1986290963 @default.
• W580688262 cites W1986408429 @default.
• W580688262 cites W1988742700 @default.
• W580688262 cites W1990078200 @default.
• W580688262 cites W1991588523 @default.
• W580688262 cites W1992350807 @default.
• W580688262 cites W1994053770 @default.
• W580688262 cites W1999668980 @default.
• W580688262 cites W2001219188 @default.
• W580688262 cites W2003192353 @default.
• W580688262 cites W2005248343 @default.
• W580688262 cites W2007782538 @default.
• W580688262 cites W2008030419 @default.
• W580688262 cites W2008916581 @default.
• W580688262 cites W2009677768 @default.
• W580688262 cites W2010705030 @default.
• W580688262 cites W2013485244 @default.
• W580688262 cites W2015644147 @default.
• W580688262 cites W2018998761 @default.
• W580688262 cites W2019043300 @default.
• W580688262 cites W2019573100 @default.
• W580688262 cites W2021769734 @default.
• W580688262 cites W2024302689 @default.
• W580688262 cites W2027335142 @default.
• W580688262 cites W2029229070 @default.
• W580688262 cites W2029789274 @default.
• W580688262 cites W2030303923 @default.
• W580688262 cites W2032848771 @default.
• W580688262 cites W2033162609 @default.
• W580688262 cites W2033966791 @default.
• W580688262 cites W2034680734 @default.
• W580688262 cites W2035989409 @default.
• W580688262 cites W2036967869 @default.
• W580688262 cites W2038154508 @default.
• W580688262 cites W2042628081 @default.
• W580688262 cites W2043294920 @default.
• W580688262 cites W2048389579 @default.
• W580688262 cites W2051203972 @default.
• W580688262 cites W2053364576 @default.
• W580688262 cites W2055128799 @default.
• W580688262 cites W2056222185 @default.
• W580688262 cites W2057961266 @default.
• W580688262 cites W2058806296 @default.
• W580688262 cites W2060136712 @default.
• W580688262 cites W2060833841 @default.
• W580688262 cites W2061536169 @default.
• W580688262 cites W2061663237 @default.
• W580688262 cites W2061988463 @default.
• W580688262 cites W2063152098 @default.
• W580688262 cites W2064943663 @default.
• W580688262 cites W2065758141 @default.
• W580688262 cites W2067761886 @default.
• W580688262 cites W2068555261 @default.
• W580688262 cites W2074097432 @default.
• W580688262 cites W2074650715 @default.
• W580688262 cites W2076823089 @default.
• W580688262 cites W2086578727 @default.
• W580688262 cites W2087312216 @default.
• W580688262 cites W2089196766 @default.
• W580688262 cites W2092169443 @default.
• W580688262 cites W2092519115 @default.
• W580688262 cites W2096057999 @default.
• W580688262 cites W2097096070 @default.
• W580688262 cites W2099088585 @default.
• W580688262 cites W2103244521 @default.
• W580688262 cites W2107962002 @default.
• W580688262 cites W2115155004 @default.
• W580688262 cites W2121850852 @default.
• W580688262 cites W2122576167 @default.
• W580688262 cites W2126249296 @default.
• W580688262 cites W2127048088 @default.
• W580688262 cites W2128320141 @default.
• W580688262 cites W2130828569 @default.
• W580688262 cites W2132125330 @default.
• W580688262 cites W2132463881 @default.
• W580688262 cites W2133256613 @default.
• W580688262 cites W2133932878 @default.

• next