Dactolisib tosylate is also known as NVP-BEZ 235 Tosylate. NVP-BEZ235 is an imidazo[4,5-c]quinoline derivative that inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. The IC50s for PI3Kα, β, γ, δ are 4, 75, 7, 5 nM, respectively. It is also found to be as active against the mutant PI3KαE545K or PI3KαH1047R with IC50s of 5.7 and 4.6 nM, respectively. In human tumor cell lines, it is able to effectively and specifically block the dysfunctional activation of the PI3K pathway, inducing G1 arrest. PTEN-null cell lines PC3M and U87MG shows a dose-dependent reduction in cell proliferation when treated with increasing concentrations of NVP-BEZ235, with an average GI50 of 10 to 12 nM. In Vivo NVP-BEZ235 is well tolerated, displays disease stasis when administered orally, and enhances the efficacy of other anticancer agents. At a dose of 50 mg/kg, NVP-BEZ235 appears rapidly in plasma with a Cmax of 1.68 μM at 0.5 h and a C24h of 0.03 μM.
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Dactolisib, also known as BEZ235, is a dual inhibitor of the phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. It has been extensively studied for its potential therapeutic applications in cancer treatment and other diseases. This paper will provide an overview of the synthesis and extraction methods, chemical structure and biological activity, biological effects, applications, and future perspectives and challenges of dactolisib.
CC-115 hydrochloride is a inhibitor of mTOR/DNA-PK (IC50= 21/ 13 nM).IC50 value: 21 nM (for mTOR), 13 nM (for DNA-PK)Target: mTOR, DNA-PKin vitro: The IC50 values for CC-115 are >10 μM against a panel of CYP enzymes and >33 μM for the hERG ion channel. When screened in a single point assay at 10 μM against a Cerep receptor and enzyme panel only one target was inhibited >50% (PDE3, IC50 = 0.63 μM).in vivo: CC-115 shows good PK profiles across multiple species with 53%, 76%, and 100% oral bioavailability in mouse, rat, and dog, respectively. CC-115, with favorable physicochemical and pharmacokinetic properties, demonstrates mTOR pathway inhibition and tumor growth inhibition, as well as a good safety profile, suitable for clinical development.
Losartan-d4 Carboxylic Acid is a deuterated analog of Losartan, which is a widely used angiotensin II receptor antagonist. Losartan-d4 Carboxylic Acid is a labeled compound that is used in various research studies, including drug development, clinical trials, and environmental research. This paper aims to provide a comprehensive review of Losartan-d4 Carboxylic Acid, including its method of synthesis or extraction, chemical structure, biological activity, biological effects, applications, future perspectives, and challenges.
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