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Chemical compound From Wikipedia, the free encyclopedia
Dactolisib (codenamed NVP-BEZ235 and BEZ-235, also known as RTB101) is an imidazoquinoline derivative acting as a PI3K inhibitor.[1] It also inhibits mTOR.[2] It is being investigated as a possible cancer treatment.[3]
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Preferred IUPAC name
2-Methyl-2-{4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl]phenyl}propanenitrile | |
Other names
NVP-BEZ235; BEZ-235; RTB101 | |
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Properties | |
C30H23N5O | |
Molar mass | 469.548 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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It has been shown to be toxic to Waldenström's macroglobulinemia cells.[4]
It was the first PI3K inhibitor to enter clinical trials, in 2006.[5]
A phase IB/II clinical trial for locally advanced or metastatic HER2 negative breast cancer has completed.[6]
A phase II clinical trial for advanced pancreatic neuroendocrine tumors (pNET) had initially reported results, but was later terminated because insufficient normal tissue tolerance to the drug.[7] A phase I clinical trial of BEZ235 in patients with advanced renal cell carcinoma had to be terminated prematurely due to toxicity and a lack of clinical efficacy .[8] Another Phase Ib study on patients with various solid cancers found severe normal tissue toxicity as well when BEZ235/Dactolisib was administered in combination with the mTOR inhibitor Everolimus. The authors concluded that the combination of both drugs demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity .[9] A phase I study of BEZ-235 to treat acute lymphoid leukaemia was initiated in 2012, but no results were published since then.[10]
A phase 2a randomized, placebo-controlled clinical trial published in 2018 showed that everolimus in combination with dactolisib decreased the rate of reported infections in an elderly population.[11]
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