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- W2215668545 abstract "The prominent role for the drug efflux pump ABCB1 (P-glycoprotein) in mediating resistance to chemotherapy was first suggested in 1976 and sparked an incredible drive to restore the efficacy of anticancer drugs. Achieving this goal seemed inevitable in 1982 when a series of calcium channel blockers were demonstrated to restore the efficacy of chemotherapy agents. A large number of other compounds have since been demonstrated to restore chemotherapeutic sensitivity in cancer cells or tissues. Where do we stand almost three decades since the first reports of ABCB1 inhibition? Unfortunately, in the aftermath of extensive fundamental and clinical research efforts the situation remains gloomy. Only a small handful of compounds have reached late stage clinical trials and none are in routine clinical usage to circumvent chemoresistance. Why has the translation process been so ineffective? One factor is the multifactorial nature of drug resistance inherent to cancer tissues; ABCB1 is not the sole factor. However, expression of ABCB1 remains a significant negative prognostic indicator and is closely associated with poor response to chemotherapy in many cancer types. The main difficulties with restoration of sensitivity to chemotherapy reside with poor properties of the ABCB1 inhibitors: (1) low selectivity to ABCB1, (2) poor potency to inhibit ABCB1, (3) inherent toxicity and/or (4) adverse pharmacokinetic interactions with anticancer drugs. Despite these difficulties, there is a clear requirement for effective inhibitors and to date the strategies for generating such compounds have involved serendipity or simple chemical syntheses. This chapter outlines more sophisticated approaches making use of bioinformatics, combinatorial chemistry and structure informed drug design. Generating a new arsenal of potent and selective ABCB1 inhibitors offers the promise of restoring the efficacy of a key weapon in cancer treatment – chemotherapy." @default.
- W2215668545 created "2016-06-24" @default.
- W2215668545 creator A5052311197 @default.
- W2215668545 creator A5053463680 @default.
- W2215668545 creator A5066853094 @default.
- W2215668545 date "2009-10-05" @default.
- W2215668545 modified "2023-09-30" @default.
- W2215668545 title "Generating Inhibitors of P-Glycoprotein: Where to, Now?" @default.
- W2215668545 cites W1271389891 @default.
- W2215668545 cites W1481486686 @default.
- W2215668545 cites W1526872663 @default.
- W2215668545 cites W1561870857 @default.
- W2215668545 cites W1562542189 @default.
- W2215668545 cites W1570070844 @default.
- W2215668545 cites W1578896110 @default.
- W2215668545 cites W1591356314 @default.
- W2215668545 cites W1595051082 @default.
- W2215668545 cites W1595188935 @default.
- W2215668545 cites W1780912673 @default.
- W2215668545 cites W1807250678 @default.
- W2215668545 cites W1925223276 @default.
- W2215668545 cites W1949997781 @default.
- W2215668545 cites W1964118830 @default.
- W2215668545 cites W1964286235 @default.
- W2215668545 cites W1964303330 @default.
- W2215668545 cites W1965455284 @default.
- W2215668545 cites W1967331103 @default.
- W2215668545 cites W1967839568 @default.
- W2215668545 cites W1969999093 @default.
- W2215668545 cites W1970963835 @default.
- W2215668545 cites W1971570097 @default.
- W2215668545 cites W1973501200 @default.
- W2215668545 cites W1976815300 @default.
- W2215668545 cites W1977032620 @default.
- W2215668545 cites W1977944550 @default.
- W2215668545 cites W1980998456 @default.
- W2215668545 cites W1981893537 @default.
- W2215668545 cites W1983318447 @default.
- W2215668545 cites W1983327716 @default.
- W2215668545 cites W1987641460 @default.
- W2215668545 cites W1987792429 @default.
- W2215668545 cites W1989310657 @default.
- W2215668545 cites W1989502449 @default.
- W2215668545 cites W1992633542 @default.
- W2215668545 cites W1992787746 @default.
- W2215668545 cites W1992867510 @default.
- W2215668545 cites W1994348363 @default.
- W2215668545 cites W1995238258 @default.
- W2215668545 cites W1995452398 @default.
- W2215668545 cites W1995852445 @default.
- W2215668545 cites W1997929799 @default.
- W2215668545 cites W2002808451 @default.
- W2215668545 cites W2006439869 @default.
- W2215668545 cites W2006721545 @default.
- W2215668545 cites W2010004274 @default.
- W2215668545 cites W2010099401 @default.
- W2215668545 cites W2010689523 @default.
- W2215668545 cites W2011027855 @default.
- W2215668545 cites W2012334764 @default.
- W2215668545 cites W2012495753 @default.
- W2215668545 cites W2012719422 @default.
- W2215668545 cites W2012845533 @default.
- W2215668545 cites W2013329423 @default.
- W2215668545 cites W2015365345 @default.
- W2215668545 cites W2016756053 @default.
- W2215668545 cites W2018755505 @default.
- W2215668545 cites W201908734 @default.
- W2215668545 cites W2020889790 @default.
- W2215668545 cites W2021759214 @default.
- W2215668545 cites W2023520902 @default.
- W2215668545 cites W2024250662 @default.
- W2215668545 cites W2024962401 @default.
- W2215668545 cites W2025907258 @default.
- W2215668545 cites W2026610312 @default.
- W2215668545 cites W2027843873 @default.
- W2215668545 cites W2028533496 @default.
- W2215668545 cites W2030867539 @default.
- W2215668545 cites W2033767311 @default.
- W2215668545 cites W2034957642 @default.
- W2215668545 cites W2035253718 @default.
- W2215668545 cites W2035506170 @default.
- W2215668545 cites W2036690838 @default.
- W2215668545 cites W2041133307 @default.
- W2215668545 cites W2041209857 @default.
- W2215668545 cites W2041833179 @default.
- W2215668545 cites W2045755433 @default.
- W2215668545 cites W2045831118 @default.
- W2215668545 cites W2046311259 @default.
- W2215668545 cites W2047282772 @default.
- W2215668545 cites W2047705402 @default.
- W2215668545 cites W2048083250 @default.
- W2215668545 cites W2048634673 @default.
- W2215668545 cites W2048679896 @default.
- W2215668545 cites W2049376982 @default.
- W2215668545 cites W2049520769 @default.
- W2215668545 cites W2050205112 @default.
- W2215668545 cites W2052007165 @default.
- W2215668545 cites W2053159064 @default.