Dactolisib (BEZ235, NVP-BEZ235)

Catalog No.S1009

Dactolisib (BEZ235, NVP-BEZ235) Chemical Structure

Molecular Weight(MW): 469.55

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell.

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Cited by 82 Publications

11 Customer Reviews

  • Level of phospho-proteins in RTK and PI3K–Akt–mTOR pathways in treated tumours, detected with western blot.

    Nature, 2017, 728-732. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Relative kinase activities of p110α mutants and the inhibitory effect of PI3K inhibitors against hotspot mutants of p110α. A, recombinant FLAG-tagged PI3K p110α/p85α protein complex produced in 293T cells was immunoprecipitated , and the immunoprecipitates were used for the quantitative PI3K-HTRF assay (32).

    B, effect of three PI3K inhibitors (ZSTK474, LY294002, and NVP-BEZ235) on the enzymatic activity of two hotspot mutants (E545K and H1047R) p110α compared with the wild-type. No striking difference was observed in the IC50 concentrations of these inhibitors between wild-type and mutant p110α.
     

     

    Cancer Res 2010 70, 4982-4994. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • A, ANOVA of IC50 values of the dual PI3K/mTOR inhibitor NVP-BEZ235 in 23 melanoma cell lines showing no significant difference in sensitivity to this compound in B-Raf mutant and Braf wild-type cells. B, decreases in pAkt and pP70S6K in a dose and time-dependent fashion in 2 melanoma cell lines treated with NVP-BEZ235. pP70S6K levels are undetectable at all concentrations and time points studied, whereas levels of pAkt start rising again after 4 hours of drug exposure in a dose-dependent fashion. C, clonogenic assays in 2 melanoma cell lines (YUVON and YUSIK) treated with NVP-BEZ235 at different concentrations. NVPBEZ235 was effective in inhibiting colony formation at low nanomolar concentrations.

    Clin Cancer Res 2010 16, 6029-6039. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.

    Breast Cancer Res 2011 13, R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • TAM (10 nM) agonistic behavior in MCF7/IGF-1R cells is not inhibited by phosphatidylinositol 3-kinase/Akt inhibitor BEZ235. (a) Inhibitory effects of kinase inhibitors BMS-536924, U0126 and BEZ235 on agonistic effect of TAM (10 nM) in the presence of IGF-1 (100 ng/mL). **P < 0.01. (b) Inhibitory effects of phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor BEZ235 at various dose ranges on IGF-1R signaling. (c) Agonistic behavior of TAM (10 nM) in response to BEZ235 kinase inhibitor. (-), no BEZ235. Results are representative of three independent experiments. Data are expressed as means ± SD.

    Breast Cancer Res 2011 13:R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    ZSTK474 and GDC-0941 selectively inhibit class I PI3K over mTOR. (A) Inhibition profiles of the selected five PI3K inhibitors for mTOR. Data shown are mean±SD (n = 3), representative of 2 or 3 independent experiments. (B) IC50 values of the PI3K inhibitors for mTOR. (C) Selectivity of each PI3K inhibitor for PI3Ka over mTOR. The selectivity index is expressed as the ratio of the IC50 value for mTOR over that for PI3Ka. The IC50 values of ZSTK474, NVP-BEZ235 and LY294002 for PI3Ka are 0.016, 0.007 and 0.6 μM, respectively, as reported previously by us.

     

     

    Eur J Cancer 2010 46, 1111-1121. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • (B) The effects of AZD2014, BEZ235, lapatinib, LEE011, pazopanib on PI3K/AKT signaling in sarcoma PDC line were determined by immunoblotting analysis. Cells were treated with 1 μM of the indicated drugs for 72 h.

    Transl Oncol, 2016, 9(3):197-202. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    The effects of LY294002, rapamycin and NVP-BEZ235 on activation of PI3K-Akt-mTOR pathway in hepatocytes. (a) The mRNA expression (PI3K, Akt, mTOR, raptor) by Real-Time PCR, (b) protein expression (PI3K, Akt, mTOR, S6K) by ELISA kits; (c) protein expression of S6K and P-S6K by western blotting. The different letters indicated significant differences (P <0.05). LY = LY294002; rapa = rapamycin; NVP = NVP-BEZ235.

    Animal, 2016, 10(8):1319-27. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  

    FIG. 4. Phospholipase A2 group 4A (PLA2G4A) expression was increased after BEZ235 treatment in basal-like xenografts. The bar graph shows the quantification of the immunoblots (mean±SD). PLA2G4A, Ethanolamine kinase 1 and 2 (ETNK1/2), Choline kinase alpha/beta (ChoKA/B), and β-actin protein expression were examined by immunoblotting of tissue samples after MRS experiments [control group (n= 5) and BEZ235-treated group (n=7)]. This demonstrated a higher expression of PLA2G4A protein ( P=0.005), but no changes in ETNK1 and ChoKA/B in samples from basal-like xenografts treated with BEZ235.

    Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

Description Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell.
Targets
p110α [1]
(Cell-free assay)
p110γ [1]
(Cell-free assay)
mTOR (p70S6K) [1]
(Cell-free assay)
p110δ [1]
(Cell-free assay)
ATR [8]
(3T3TopBP1-ER cells)
4 nM 5 nM 6 nM 7 nM 21 nM
In vitro

BEZ235 significantly reduces the phosphorylation levels of the mTOR activated kinase p70S6K. BEZ235 results in a reduction of S235/S236P-RPS6 levels with IC50 of 6.5 nM. The activity of BEZ235 against mTOR is determined using a biochemical mTOR K-LISA assay with IC50 of 20.7 nM. BEZ235 shows slightly lower activity against its β paralogue with IC50 of 75 nM. The PI3K/Akt/mTOR pathway is often constitutively activated in human tumor cells. BEZ235 blocks PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. Both PTEN-null cell lines PC3M and U87MG show a dose-dependent reduction in cell proliferation when treated with increasing concentrations of BEZ235 with an average GI50 of 10-12 nM. [1] BEZ235 is an mTORC1/2 catalytic inhibitor. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei MkTLRY51cW2rY4LvZolidCCDc4PhfS=> MojuNVghcA>? MXrEUXNQ NE\LVmZCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP MW[yOFgxPTl2Nh?=
MCF7 NYfyc4NNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfWbFAxNjBzLUGwNEDPxE1? NH;qOXE1QCCq MonsSG1UVw>? MnXvTWM2OD1yLkezJO69VQ>? NFzhXpUzOzh5MUmwOC=>
HCT116 NXzDTGVoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MViwMlAyNTFyMDFOwG0> Mn:zOFghcA>? MUPEUXNQ NFzaZ4ZKSzVyPUGuNVYh|ryP MnfhNlM5PzF7MES=
U87MG NH;tfotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rzSlAvODFvMUCwJO69VQ>? NYfkV5U{PDhiaB?= Ml3FSG1UVw>? MWXJR|UxRTFwM{Kg{txO M1fHS|I{QDdzOUC0
HBC4 NGroV2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUCwMlAyNTFyMDFOwG0> MmTPOFghcA>? NHH2dYhNd2diR1m1NF0uQC54MTDN NUewfpZbOjJ|M{[yOFY>
BSY1 NVv5WVN7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4OyPFAvODFvMUCwJO69VQ>? MYC0PEBp NESzdXNNd2diR1m1NF0uQC52ODDN Mkn0NlI{OzZ{NE[=
HBC5 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHsRlcxNjBzLUGwNEDPxE1? MorVOFghcA>? MoDKUI9oKEeLNUC9MVcvQDdiTR?= NIXNTIEzOjN|NkK0Oi=>
MCF7 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnGwNE4xOS1zMECg{txO M4\mdFQ5KGh? M2rjO2xw\yCJSUWwQU05NjF4IF2= MlzPNlI{OzZ{NE[=
MDA-MB-231 NGPic5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;iSFAvODFvMUCwJO69VQ>? MWS0PEBp NEjrbXpNd2diR1m1NF0uQC5yOTDN NXjEdpc6OjJ|M{[yOFY>
U251 NFHOOJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXQRXUxNjBzLUGwNEDPxE1? Mo\ZOFghcA>? NWOwRXlQVG:pIFfJOVA:NTdwNk[gUS=> M{HW[VIzOzN4MkS2
SF268 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELNT|AxNjBzLUGwNEDPxE1? NUXWRYI{PDhiaB?= NFy4V4tNd2diR1m1NF0uPy57MjDN NUP6[HFGOjJ|M{[yOFY>
SF295 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\Qc|AvODFvMUCwJO69VQ>? MWq0PEBp MWHMc4chT0l3ME2tPE4{OSCP M{HoNVIzOzN4MkS2
SF539 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXhR4wxNjBzLUGwNEDPxE1? MmP2OFghcA>? MlTMUI9oKEeLNUC9MVgvPTliTR?= NUnLeo03OjJ|M{[yOFY>
SNB75 NUH1R|VWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWSwMlAyNTFyMDFOwG0> NFuzfWs1QCCq M{LsTmxw\yCJSUWwQU05NjV6IF2= NIn6Xo0zOjN|NkK0Oi=>
SNB78 NXe1Xo04T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlW1NE4xOS1zMECg{txO NGfZOIw1QCCq MWLMc4chT0l3ME2tPE43PSCP NGPqS3EzOjN|NkK0Oi=>
HCC2998 MoHSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;xOWsxNjBzLUGwNEDPxE1? MkjOOFghcA>? Mn7PUI9oKEeLNUC9MVgvODViTR?= M4Px[lIzOzN4MkS2
KM12 NWHjc5p2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXmwMlAyNTFyMDFOwG0> NUO0OW5JPDhiaB?= MULMc4chT0l3ME2tO{42PCCP NXzhdYZnOjJ|M{[yOFY>
HT-29 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWCwMlAyNTFyMDFOwG0> MkCzOFghcA>? MUXMc4chT0l3ME2tO{44PSCP NIXKPIczOjN|NkK0Oi=>
HCT15 M4n0bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYewMlAyNTFyMDFOwG0> M4PlcFQ5KGh? Ml[4UI9oKEeLNUC9MVgvODNiTR?= NFzrW4YzOjN|NkK0Oi=>
HCT116 NFPaSWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn7DNE4xOS1zMECg{txO MWO0PEBp MmPTUI9oKEeLNUC9MVcvPjFiTR?= M2fKZVIzOzN4MkS2
NCI-H23 Mne1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYWwMlAyNTFyMDFOwG0> NUXCO405PDhiaB?= NYnSRYVbVG:pIFfJOVA:NTdwNkSgUS=> M4rTTVIzOzN4MkS2
NCI-H226 NXrMRoh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXOwMlAyNTFyMDFOwG0> NF\FZXg1QCCq M2\qXmxw\yCJSUWwQU05NjR2IF2= NV7td2N7OjJ|M{[yOFY>
NCI-H522 NXfQW49PT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX[wMlAyNTFyMDFOwG0> M3\pOFQ5KGh? NV3iNpBKVG:pIFfJOVA:NThwNEWgUS=> M4n2Z|IzOzN4MkS2
NCI-H438 NEXt[oxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{i3O|AvODFvMUCwJO69VQ>? M1jWSlQ5KGh? NXrpRlNZVG:pIFfJOVA:NThwMUGgUS=> Mon5NlI{OzZ{NE[=
A549 Moi0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljlNE4xOS1zMECg{txO NULYbmF1PDhiaB?= NH3OXo1Nd2diR1m1NF0uQC5yNzDN Mnf1NlI{OzZ{NE[=
DMS273 MnziS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmO1NE4xOS1zMECg{txO M2q0[|Q5KGh? M17IU2xw\yCJSUWwQU04NjhyIF2= M{jxPFIzOzN4MkS2
DMS114 MmjyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUmwMlAyNTFyMDFOwG0> M4LZW|Q5KGh? MUHMc4chT0l3ME2tPE4{QSCP Mkf2NlI{OzZ{NE[=
LOXIMVI MoOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zGPVAvODFvMUCwJO69VQ>? M1vEcVQ5KGh? NVy5XFFOVG:pIFfJOVA:NThwNk[gUS=> NYLmXGFxOjJ|M{[yOFY>
OVCAR3 NHzIb5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonZNE4xOS1zMECg{txO NFzvUnY1QCCq NVy1OXlPVG:pIFfJOVA:NThwMUegUS=> NF\0OZkzOjN|NkK0Oi=>
OVCAR4 NWTa[XRJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnmNE4xOS1zMECg{txO Mn;XOFghcA>? MVTMc4chT0l3ME2tPE42QCCP NUTDW3FTOjJ|M{[yOFY>
OVCAR5 NHzjZXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHkNE4xOS1zMECg{txO M37zVVQ5KGh? M3nOOWxw\yCJSUWwQU04NjV5IF2= MXuyNlM{PjJ2Nh?=
OVCAR8 M3fYVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYWwMlAyNTFyMDFOwG0> MofoOFghcA>? NIHkcZlNd2diR1m1NF0uPy56NDDN MX6yNlM{PjJ2Nh?=
SKOV3 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPvNE4xOS1zMECg{txO M3naVlQ5KGh? NETY[3ZNd2diR1m1NF0uQC52MTDN MVqyNlM{PjJ2Nh?=
RXF631L NWPBOoxDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWqwMlAyNTFyMDFOwG0> Mk\ROFghcA>? MkHQUI9oKEeLNUC9MVgvOjFiTR?= MoO1NlI{OzZ{NE[=
ACHN M3rU[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TpbFAvODFvMUCwJO69VQ>? NEe0TYM1QCCq MlvJUI9oKEeLNUC9MVcvQTViTR?= MXOyNlM{PjJ2Nh?=
St-4 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoH3NE4xOS1zMECg{txO NInPSlY1QCCq MkTuUI9oKEeLNUC9MVcvPDdiTR?= NXXtbnBIOjJ|M{[yOFY>
MKN1 MnPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVewMlAyNTFyMDFOwG0> MUO0PEBp M{jON2xw\yCJSUWwQU05NjRzIF2= NF\LeoozOjN|NkK0Oi=>
MKN7 NHT3SHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUX1O|VXOC5yMT2xNFAh|ryP M3LvelQ5KGh? M{Pub2xw\yCJSUWwQU04NjZ6IF2= NEHxW|MzOjN|NkK0Oi=>
MKN28 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHsNE4xOS1zMECg{txO NGHBfJk1QCCq Ml:5UI9oKEeLNUC9MVcvODdiTR?= MmfCNlI{OzZ{NE[=
MKN45 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml63NE4xOS1zMECg{txO MmHBOFghcA>? MmXRUI9oKEeLNUC9MVgvOzRiTR?= NXj4N4dDOjJ|M{[yOFY>
MKN74 M2LQbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn6xNE4xOS1zMECg{txO NHPIOY01QCCq M2Tl[2xw\yCJSUWwQU04NjR{IF2= MXqyNlM{PjJ2Nh?=
DU145 NIS0VY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2q3N|AvODFvMUCwJO69VQ>? NX\EbZFMPDhiaB?= M1vFcWxw\yCJSUWwQU05NjF4IF2= NFzLU3UzOjN|NkK0Oi=>
PC3 M4PHWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TMXFAvODFvMUCwJO69VQ>? M1LiR|Q5KGh? NUDuVIV6VG:pIFfJOVA:NThwNk[gUS=> M{mzfFIzOzN4MkS2
Trypanosoma brucei brucei M4PBS2Z2dmO2aX;uJGF{e2G7 M17JS|IxOCCwTR?= NYPPSGIzOTJiaB?= MnHySG1UVw>? M4freWRm[3KnYYPlJIlvKHCqb4PwbI91cWS7bDDpco9{cXSxbDDwbI9{eGijdHWgcIV3\Wx? M2rxUlI1QDB3OUS2
Trypanosoma brucei brucei NHX0OGdHfW6ldHnvckBCe3OjeR?= MVGxPEBp MUHEUXNQ MmO5TY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? MXuyOFgxPTl2Nh?=
Trypanosoma brucei brucei M1HDfmZ2dmO2aX;uJGF{e2G7 NVeyT|dyOjByIH7N MXSxNkBp MVvEUXNQ MnuySYZn\WO2IH;uJJNxcGmwZ3;tfYxmcW5ibHX2[Yw> MnPVNlQ5ODV7NE[=
Trypanosoma brucei brucei Mn33SpVv[3Srb36gRZN{[Xl? MXmyNFAhdk1? NXW4WJU5OTJiaB?= NH3GUZlFVVOR MV7F[oZm[3Rib36gdIhwe3CqYYTp[Jlt[2ixbHnu[UBt\X[nbB?= NVTtSo1XOjR6MEW5OFY>
UM-UC-3 Mke0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjRPWxKSzVyPUOxOUBxVQ>? NWTFc5hyW0GQR1XS
SBC-1 M362OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHs[|RKSzVyPUe0NkBxVQ>? NYPWSYpKW0GQR1XS
MKN1 MlmzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3m5RmlEPTB;Mj64JI5O M{\3SXNCVkeHUh?=
NCI-H720 M3HJOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTNwNUegcm0> NWHEVWlSW0GQR1XS
BFTC-909 MlewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX\JR|UxRTNwN{Ggcm0> Ml7iV2FPT0WU
BPH-1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3nwZ2lEPTB;ND63OkBvVQ>? MWPTRW5ITVJ?
PC-3 Ml\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlX3TWM2OD13LkC5JI5O NYfZO4o2W0GQR1XS
AN3-CA M3T6Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\4c|ZrUUN3ME21MlU3KG6P NFXrOG5USU6JRWK=
HN NXPLZ2JLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXOTWM2OD13Lkm2JI5O M1zENXNCVkeHUh?=
HCC2218 NYTLenBxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTZwNkGgcm0> Mlq3V2FPT0WU
KP-4 MmXCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HHfGlEPTB;NzDuUS=> M4LtZXNCVkeHUh?=
LU-139 NG\JOIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3uN|FKSzVyPUeuO|chdk1? NX;nSVhsW0GQR1XS
ETK-1 MlqzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYj6NnR5UUN3ME23Mlg5KG6P NGSzOWRUSU6JRWK=
Ramos-2G6-4C10 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnJR|UxRThwNEmgcm0> NWnZSnBuW0GQR1XS
MHH-PREB-1 MlW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzRTWM2OD17LkGyJI5O M{XPR3NCVkeHUh?=
DU-4475 NIPiZ4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\TUFRKSzVyPUmuOFQhdk1? NXjJPZd1W0GQR1XS
NCI-H1666 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHLselRKSzVyPUmuO|Ehdk1? M{K4UnNCVkeHUh?=
CAMA-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLxUm5KSzVyPUmuPEBvVQ>? MVvTRW5ITVJ?
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SK-N-DZ MnO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{HZb2lEPTB;Mj64OlM5OSEQvF2= NFrGOWRUSU6JRWK=
NCI-H82 Mn3uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPqSGNKSzVyPUKuPVA{PjlizszN MmewV2FPT0WU
JVM-2 Mki0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn7BTWM2OD1|LkCzNVg5KM7:TR?= NXPTR21KW0GQR1XS
SW1116 NEXId|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2T0dGlEPTB;Mz6wOVQyOSEQvF2= Mlz6V2FPT0WU
MDA-MB-453 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DmcmlEPTB;Mz6xNFQ{QSEQvF2= NGfOOIdUSU6JRWK=
Calu-6 M3vNZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3q4OmlEPTB;Mz6xPVk4KM7:TR?= NYn3OFRlW0GQR1XS
SHP-77 M4LHWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1i5TGlEPTB;Mz61Nlgh|ryP MV\TRW5ITVJ?
Capan-2 NGLsV5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XzT2lEPTB;ND6zNlU5OSEQvF2= NIHqWWxUSU6JRWK=
SW948 Mn3TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrvTWM2OD12Lke0O|c6KM7:TR?= MXvTRW5ITVJ?
HDLM-2 NYH2OWJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVHJR|UxRTVwMEe3NlUh|ryP M1S2N3NCVkeHUh?=
LAN-6 MoP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzhVnRsUUN3ME22MlIyPDl3IN88US=> M2jVcnNCVkeHUh?=
LU-135 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fxdGlEPTB;Nj60N|A4PyEQvF2= M1LXXXNCVkeHUh?=
T84 NVnsS41VT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlP5TWM2OD14Lkm4OlQh|ryP NUPxV3dVW0GQR1XS
CAPAN-1 Mk\pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DLOWlEPTB;Nz62NlI{OyEQvF2= M4j3U3NCVkeHUh?=
SW1417 MmLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLRV|V6UUN3ME23MlkyPzNzIN88US=> MWTTRW5ITVJ?
BALL-1 NWm4N5VLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWDJR|UxRThwNUC0NFkh|ryP MnjiV2FPT0WU
HT-29 NHS0e3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLHTWM2OD17LkC3OVk6KM7:TR?= MkHFV2FPT0WU
C3A NV;r[nNbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnGwTWM2OD17Lki4N|k1KM7:TR?= NE\zfotUSU6JRWK=
NCI-H1993 NYPFXppiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{n2OGlEPTB;MUCuOVA5OSEQvF2= NYDwNXRYW0GQR1XS
SK-MEL-1 MnTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTOTmt2UUN3ME2xNU43Ojh7IN88US=> NX3KN|F3W0GQR1XS
DU-145 NWDO[5RkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4rwZ2lEPTB;MUSuOVA2OiEQvF2= Mn;UV2FPT0WU
KP-N-YN MnzZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLLTWM2OD1zND61NVA{KM7:TR?= NE\scJJUSU6JRWK=
CCRF-CEM MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DldmlEPTB;MUSuO|gxQSEQvF2= NGXEU29USU6JRWK=
ZR-75-30 NWrybYNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2H1RWlEPTB;MU[uN|MxOyEQvF2= M1fpOnNCVkeHUh?=
A673 MmnBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXMSGVKSzVyPUKwMlU2ODdizszN NFLFb3RUSU6JRWK=
K-562 NYCzUFQ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUPJR|UxRTJ6LkSxPFMh|ryP MWnTRW5ITVJ?

... Click to View More Cell Line Experimental Data

In vivo BEZ235 induces regression of the tumors (69%) without statistically significant effect on body weight gain. Altogether, these preliminary in vivo efficacy results show that BEZ235 causes disease stasis when administered orally as a single agent and can enhance the efficacy of other anticancer agents when used in combination studies. [1]

Protocol

Kinase Assay:

[1]

+ Expand

In vitro Protein Kinase, PI3K, and mTOR Assays:

PI3Kα, β, and δ proteins are composed of the iSH2 domain of p85 NH2-terminally fused to the full-length protein p110 protein, with the exception of α that also does not contain the last 20 amino acids. PI3Kγ is produced as full-length protein deleted for its first 144 amino acids. All constructs are fused to a COOH-terminal His tag for convenient purification and then cloned into the pBlue-Bac4.5 (for α, β, and δ isoforms) or pVL1393 (for γ isoform) plasmids. The different vectors are then cotransfected with BaculoGold WT genomic DNA using methods recommended by the vendor for production of the respective recombinant baculoviruses and proteins. BEZ235 are tested for their activity against PI3K using a Kinase-Glo assay. The kinase reaction is done in 384-well black plate. Each well is loaded with 50 μL of test items (in 90% DMSO) and 5 μL reaction buffer containing 10 μg/mL PI substrate (l-α-phosphatidylinositol; Avanti Polar Lipids; prepared in 3% octyl-glucoside) and the PI3K proteins (10, 25, 10, and 150 nM of p110α, p110β, p110δ, and p110γ, respectively) are then added to it. The reaction is started by the addition of 5 μL of 1 μM ATP prepared in the reaction buffer and is incubated for either 60 (for p110α, p110β, and p110δ) or 120 min (for p110γ). It is terminated by the addition of 10 μL Kinase-Glo buffer. The plates are then read in a Synergy 2 reader for luminescence detection.
Cell Research:

[2]

+ Expand
  • Cell lines: HCT116, DLD-1 and SW480 cells
  • Concentrations: 0-1 μM
  • Incubation Time: 48 hours
  • Method:

    The human CRC cell lines, HCT116 (PIK3CA mutant; kinase domain at H1047R), DLD-1 (PIK3CA mutant; helical domain at E545K), and SW480 (PIK3CA wild-type) and isogenic DLD-1 PIK3CA mutant as well as wild-type cells are maintained in DMEM with 10% FBS and 1 × Penicillin/Streptomycin. Cells are plated at different initial densities (HCT116: 3 × 103 cells/well, DLD-1: 5.5 × 103 cells/well, SW480: 4.5 × 103 cells/well, DLD-1 PIK3CA mutant: 7 × 103 cells/well, and DLD-1 PIK3CA wild-type: 9 × 103 cells/well) to account for differential growth kinetics. After 16 hours, cells are incubated with increasing concentrations of BEZ235, and the drug-containing growth medium is changed every 24 hours. Cell viability is assessed 16 hours after the initial plating and 48 hours after initiation of drug treatment using the colorimetric MTS assay CellTiter 96® AQueous One Solution Cell Proliferation Assay, as per the manufacturer's instructions. Cell viability after drug treatment is normalized to that of untreated cells also grown for 48 hours. For western blot analysis, cells are plated with zero or maximum inhibitory dose (500 nM) BEZ235 for 2, 6, 24, or 48 hours.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: Female Harlan athymic nude mice
  • Formulation: NMP/polyethylene glycol 300 (10/90, v/v)
  • Dosages: 45 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMF 18 mg/mL warmed (38.33 mM)
DMSO 0.01 mg/mL (0.02 mM)
Water Insoluble
In vivo Add solvents individually and in order:
NMP+polyethylene glycol 300 (10+90, v+v)
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 469.55
Formula

C30H23N5O

CAS No. 915019-65-7
Storage powder
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00620594 Completed Breast Cancer|Advanced Solid Tumors|Cowden Syndrome Novartis Pharmaceuticals|Novartis December 21, 2006 Phase 1
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01717898 Terminated Castrate-resistant Prostate Cancer Patients. Charles Ryan|Novartis Pharmaceuticals|University of California, San Francisco January 2013 Phase 1|Phase 2
NCT01658436 Completed Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis November 2012 Phase 2
NCT01628913 Terminated Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis October 2012 Phase 2
NCT01690871 Withdrawn Malignant PEComa (Perivascular Epithelioid Cell Tumors) Novartis Pharmaceuticals|Novartis September 2012 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

    With difficulties in dissolving BEZ235, How can I improve its solubility?

  • Answer:

    For in vivo study, we suggest the vehicle solution NMP/polyethylene glycol 300 (10/90, v/v). Please dissolve BEZ235 in NMP as more as possible. You can sonicate and warm it in water bath for a while. Then dilute with PEG 300.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID