BEZ235 (Tosylate)

Names

[ Name ]:
BEZ235 (Tosylate)

[Synonym ]:
BEZ235 Tosylate||BEZ-235 Tosylate
NVP-BEZ235 tosylate
NVP-BEZ235-ANA
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile monotosylate
Dactolisib Tosylate
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile monotosylate salt
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]propionitrile p-toluenesulfonate
BEZ235 Tosylate
BEZ235 (Tosylate)

Biological Activity

[Description]:

BEZ235 Tosylate is a dual PI3K and mTOR kinase inhibitor with IC50 values of 4, 75, 7, 5 nM for PI3Kα, β, γ, δ, respectively. BEZ235 inhibits mTORC1 and mTORC2.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

[Target]

p110α:4 nM (IC50)

p110α-H1047R:4.6 nM (IC50)

p110α-E545K:5.7 nM (IC50)

p110γ:5 nM (IC50)

p110δ:7 nM (IC50)

p110β:75 nM (IC50)

mTOR:20.7 nM (IC50)

mTORC1

mTORC2

Autophagy

[In Vitro]

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[1].

[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[1].

[Kinase Assay]

NVP-BEZ235 is dissolved in DMSO to a stock concentration of 10 mM and diluted with cell media. The kinase reaction is done in 384-well black plate. Each well is loaded with 50 nL of test items (in 90% DMSO) and 5 μL reaction buffer containing 10 μg/mL PI substrate and the PI3K proteins (10, 25, 10, and 150 nM of p110α, p110β, p110γ, and p110δ, respectively) are then added. The reaction is started by the addition of 5 μL of 1 μM ATP prepared in the reaction buffer and ran for either 60 or 120 min and subsequently terminated by the addition of 10 μL Kinase-Glo buffer. The plates are then read in a Synergy 2 reader for luminescence detection[1].

[Animal admin]

Mice: The NVP-BEZ235 powder is dissolved in NMP on sonication, and the remaining volume of polyethylene glycol 300 is added to a concentration of 5 mg/mL. The application volume is 10 mL/kg. For analytics, frozen tissues are minced and then homogenized in an equal volume of ice-cold PBS and centrifugation, supernatants are analyzed. Samples are then eluted with a linear gradient of 10% to 90% (v/v) acetonitrile in water containing 0.05% (v/v) trifluoroacetic acid over a period of 20 min at a flow rate of 1 mL/min. The compounds are detected by UV absorbance at 340 nm, and concentrations are determined by the external standard method using peak heights[1].

[References]

[1]. Maira SM, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther, 2008, 7(7), 1851-1863.

[Related Small Molecules]

Chemical & Physical Properties

[ Molecular Formula ]:
C₃₇H₃₁N₅O₄S

[ Molecular Weight ]:
641.73800

[ Exact Mass ]:
641.21000

[ PSA ]:
139.25000

[ LogP ]:
8.21628

[ Storage condition ]:
-20°C

BEZ235 (Tosylate)

Names

Biological Activity

Chemical & Physical Properties

Related Compounds