BEZ235 (NVP-BEZ235, Dactolisib)

Catalog No.S1009

BEZ235 (NVP-BEZ235, Dactolisib) Chemical Structure

Molecular Weight(MW): 469.55

BEZ235 (NVP-BEZ235, Dactolisib) 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 78 Publications

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  • 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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. BEZ235 (NVP-BEZ235, Dactolisib) 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.

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

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description BEZ235 (NVP-BEZ235, Dactolisib) 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 M1PQcWFvfGmvaXPyc4Jq[WxiQYPzZZk> M3;CfVE5KGh? MoPYSG1UVw>? NWCyenpLSW62aYTyfZBidm:|b33hcEBi[3Srdnn0fUB4cXSqIFXDOVAhd2ZiMD6wNFI2KM7:TR?= M1LwOVI1QDB3OUS2
MCF7 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV2wMlAyNTFyMDFOwG0> MV60PEBp M{D5NWROW09? M{XDc2lEPTB;MD63N{DPxE1? NIjTO|kzOzh5MUmwOC=>
HCT116 MlHQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1HUXlAvODFvMUCwJO69VQ>? MnTTOFghcA>? NWq3[mZtTE2VTx?= MkXCTWM2OD1zLkG2JO69VQ>? M2fkclI{QDdzOUC0
U87MG M3[3VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jiclAvODFvMUCwJO69VQ>? M{\C[|Q5KGh? NUPLb2x6TE2VTx?= MnHsTWM2OD1zLkOyJO69VQ>? NV;td49JOjN6N{G5NFQ>
HBC4 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV2wMlAyNTFyMDFOwG0> Moq2OFghcA>? NW\hPFJoVG:pIFfJOVA:NThwNkGgUS=> MYOyNlM{PjJ2Nh?=
BSY1 NEC0dXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2\telAvODFvMUCwJO69VQ>? NEDFVFA1QCCq MlPLUI9oKEeLNUC9MVgvPDhiTR?= MWiyNlM{PjJ2Nh?=
HBC5 NIW2U4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUT2UIZnOC5yMT2xNFAh|ryP MXe0PEBp MlLTUI9oKEeLNUC9MVcvQDdiTR?= NIPiO4YzOjN|NkK0Oi=>
MCF7 NXzq[JNjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXuc4MxNjBzLUGwNEDPxE1? MX:0PEBp MX\Mc4chT0l3ME2tPE4yPiCP NYXwWZJxOjJ|M{[yOFY>
MDA-MB-231 NF3oZVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXuwMlAyNTFyMDFOwG0> M4TVWlQ5KGh? NVyyXY9EVG:pIFfJOVA:NThwMEmgUS=> MWSyNlM{PjJ2Nh?=
U251 NHvGS2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHoNE4xOS1zMECg{txO MV[0PEBp MULMc4chT0l3ME2tO{43PiCP M1LHOlIzOzN4MkS2
SF268 M2D3PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGrD[mMxNjBzLUGwNEDPxE1? MkfDOFghcA>? M4XyV2xw\yCJSUWwQU04Njl{IF2= MV:yNlM{PjJ2Nh?=
SF295 NFzuU4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYOwVFVNOC5yMT2xNFAh|ryP M3TGelQ5KGh? NH;hVnpNd2diR1m1NF0uQC5|MTDN M16yWVIzOzN4MkS2
SF539 M33OXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmK2NE4xOS1zMECg{txO M4PMZ|Q5KGh? M4\HS2xw\yCJSUWwQU05NjV7IF2= NI\NOHIzOjN|NkK0Oi=>
SNB75 NETXO2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{OyRlAvODFvMUCwJO69VQ>? MmXlOFghcA>? M4jJ[Gxw\yCJSUWwQU05NjV6IF2= MnTWNlI{OzZ{NE[=
SNB78 MlXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnYTXpTOC5yMT2xNFAh|ryP NWG3XoRTPDhiaB?= MWTMc4chT0l3ME2tPE43PSCP MX6yNlM{PjJ2Nh?=
HCC2998 M3\PXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnn2NE4xOS1zMECg{txO Ml;qOFghcA>? MmK3UI9oKEeLNUC9MVgvODViTR?= Mli1NlI{OzZ{NE[=
KM12 MmLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M332TFAvODFvMUCwJO69VQ>? M{TXXVQ5KGh? NFXteHlNd2diR1m1NF0uPy53NDDN Ml7jNlI{OzZ{NE[=
HT-29 M4HLcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXewMlAyNTFyMDFOwG0> MXG0PEBp MmDIUI9oKEeLNUC9MVcvPzViTR?= MXWyNlM{PjJ2Nh?=
HCT15 M3TSPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEP4T|kxNjBzLUGwNEDPxE1? M{LROFQ5KGh? MXTMc4chT0l3ME2tPE4xOyCP NFzRdnkzOjN|NkK0Oi=>
HCT116 MlvVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlqzNE4xOS1zMECg{txO M4HlclQ5KGh? M3rtNGxw\yCJSUWwQU04NjZzIF2= Mn\3NlI{OzZ{NE[=
NCI-H23 NY\m[mpPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1Pnd|AvODFvMUCwJO69VQ>? NYfscFJYPDhiaB?= M2LKbWxw\yCJSUWwQU04NjZ2IF2= MUSyNlM{PjJ2Nh?=
NCI-H226 Mm\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fsUVAvODFvMUCwJO69VQ>? NE[zdVQ1QCCq NFnlVWhNd2diR1m1NF0uQC52NDDN NW\oWVF6OjJ|M{[yOFY>
NCI-H522 M4XYS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\iUGdqOC5yMT2xNFAh|ryP MojNOFghcA>? M{n1bWxw\yCJSUWwQU05NjR3IF2= NUjwUXZKOjJ|M{[yOFY>
NCI-H438 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXPNE4xOS1zMECg{txO NUH1XodXPDhiaB?= M1zNOmxw\yCJSUWwQU05NjFzIF2= M2H5R|IzOzN4MkS2
A549 NIjqfHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTCNE4xOS1zMECg{txO NIXGb2M1QCCq Mm[wUI9oKEeLNUC9MVgvODdiTR?= NWf4TXdOOjJ|M{[yOFY>
DMS273 NV7RVHZIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3JNE4xOS1zMECg{txO Mnj3OFghcA>? Mmi4UI9oKEeLNUC9MVcvQDBiTR?= M1Pvd|IzOzN4MkS2
DMS114 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXu4W2tmOC5yMT2xNFAh|ryP M37HbFQ5KGh? MkfJUI9oKEeLNUC9MVgvOzliTR?= MmDuNlI{OzZ{NE[=
LOXIMVI NIfWNnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\FRVkxNjBzLUGwNEDPxE1? M2S5UVQ5KGh? NV\yTol1VG:pIFfJOVA:NThwNk[gUS=> MmjrNlI{OzZ{NE[=
OVCAR3 M3zlcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkXzNE4xOS1zMECg{txO NHTvPHA1QCCq MYLMc4chT0l3ME2tPE4yPyCP M36xXVIzOzN4MkS2
OVCAR4 NUnN[5ZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrXNE4xOS1zMECg{txO M2KwZVQ5KGh? MlfCUI9oKEeLNUC9MVgvPThiTR?= MUmyNlM{PjJ2Nh?=
OVCAR5 NWC4T4dbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVywMlAyNTFyMDFOwG0> NHrKclY1QCCq NUnpZ2VzVG:pIFfJOVA:NTdwNUegUS=> MmnBNlI{OzZ{NE[=
OVCAR8 NYXjeJFET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILGeoExNjBzLUGwNEDPxE1? NW\sd3JoPDhiaB?= M1nyUGxw\yCJSUWwQU04Njh2IF2= NWK1UHNCOjJ|M{[yOFY>
SKOV3 NWj5N2kzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml;ONE4xOS1zMECg{txO NYDTZ3FMPDhiaB?= NV7yT2dXVG:pIFfJOVA:NThwNEGgUS=> NVzWVm1oOjJ|M{[yOFY>
RXF631L MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPqV4oxNjBzLUGwNEDPxE1? NF3rUYc1QCCq M{\1dmxw\yCJSUWwQU05NjJzIF2= Ml3nNlI{OzZ{NE[=
ACHN NH7NUHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV2wMlAyNTFyMDFOwG0> NFP5NVU1QCCq NHTkPZpNd2diR1m1NF0uPy57NTDN M4f2OFIzOzN4MkS2
St-4 NIPoR41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\sfWpEOC5yMT2xNFAh|ryP M{fnPFQ5KGh? MX3Mc4chT0l3ME2tO{41PyCP NYnyNZU{OjJ|M{[yOFY>
MKN1 NF2yOnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2DXWlAvODFvMUCwJO69VQ>? MoS2OFghcA>? NGLuXmtNd2diR1m1NF0uQC52MTDN M17SclIzOzN4MkS2
MKN7 MoXuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{O5R|AvODFvMUCwJO69VQ>? M3:2T|Q5KGh? NHL0N4dNd2diR1m1NF0uPy54ODDN NWTUfms1OjJ|M{[yOFY>
MKN28 NEHoU3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrONE4xOS1zMECg{txO M2DVclQ5KGh? MXjMc4chT0l3ME2tO{4xPyCP MkTqNlI{OzZ{NE[=
MKN45 NHSxb|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlz3NE4xOS1zMECg{txO MVm0PEBp NFrwVpNNd2diR1m1NF0uQC5|NDDN NGPoVXAzOjN|NkK0Oi=>
MKN74 NGDxXJFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWSwMlAyNTFyMDFOwG0> NXPLOJRjPDhiaB?= Mm[xUI9oKEeLNUC9MVcvPDJiTR?= MW[yNlM{PjJ2Nh?=
DU145 M2W4b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{PHUFAvODFvMUCwJO69VQ>? NYr6ZVFFPDhiaB?= MYPMc4chT0l3ME2tPE4yPiCP NVrmfGlCOjJ|M{[yOFY>
PC3 MlvsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVewMlAyNTFyMDFOwG0> MlXTOFghcA>? M2DSVWxw\yCJSUWwQU05NjZ4IF2= MXSyNlM{PjJ2Nh?=
Trypanosoma brucei brucei NVP1cotMTnWwY4Tpc44hSXO|YYm= NVP2cWpsOjByIH7N NGDn[nYyOiCq NWfWbYVsTE2VTx?= MXjE[YNz\WG|ZTDpckBxcG:|cHjveIllgWxiaX7vd4l1d2xicHjvd5Bp[XSnIHzleoVt NFz1XVkzPDhyNUm0Oi=>
Trypanosoma brucei brucei NITQSGtHfW6ldHnvckBCe3OjeR?= M3XteFE5KGh? NVHWbmhwTE2VTx?= M2f5TGlvcGmkaYTpc44hd2ZicnXj[ZB1d3JvbXXkbYF1\WRiZX7kc4N6fG:|aYOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5idILhcpNn\XK{aX6geZB1[Wun M1Lme|I1QDB3OUS2
Trypanosoma brucei brucei NI\HSYRHfW6ldHnvckBCe3OjeR?= MX[yNFAhdk1? MXuxNkBp MnLySG1UVw>? MWLF[oZm[3Rib36gd5BpcW6pb335cIVqdiCuZY\lcC=> MmjMNlQ5ODV7NE[=
Trypanosoma brucei brucei NWLpRngyTnWwY4Tpc44hSXO|YYm= M{T6WlIxOCCwTR?= NELsUZcyOiCq M3vrWmROW09? MojoSYZn\WO2IH;uJJBpd3OyaHH0bYR6dGOqb3zpcoUhdGW4ZXy= M1XsfVI1QDB3OUS2
UM-UC-3 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTNzNTDwUS=> NHPIZ3NUSU6JRWK=
SBC-1 NXrocZFVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnLtTWM2OD15NEKgdG0> MoXoV2FPT0WU
MKN1 NH3Q[XpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3jrR2lEPTB;Mj64JI5O NVvrb2pQW0GQR1XS
NCI-H720 M{PueWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLFTWM2OD1|LkW3JI5O NEDnVGhUSU6JRWK=
BFTC-909 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjJR|UxRTNwN{Ggcm0> MnG3V2FPT0WU
BPH-1 MmXLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnPRpRKSzVyPUSuO|Yhdk1? NIfuSVVUSU6JRWK=
PC-3 NX7XUWlbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4fI[GlEPTB;NT6wPUBvVQ>? MWnTRW5ITVJ?
AN3-CA M3K2bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTVwNU[gcm0> M{jQSnNCVkeHUh?=
HN MoraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXHJR|UxRTVwOU[gcm0> M3vaVnNCVkeHUh?=
HCC2218 NW\5[JBNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33S[WlEPTB;Nj62NUBvVQ>? NV6zbWQyW0GQR1XS
KP-4 NYfpOnFjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTdibl2= NUnudGxQW0GQR1XS
LU-139 NXTVXHlGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;pcY44UUN3ME23Mlc4KG6P MXrTRW5ITVJ?
ETK-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LjNWlEPTB;Nz64PEBvVQ>? MX7TRW5ITVJ?
Ramos-2G6-4C10 MoLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRThwNEmgcm0> NYDYTHhIW0GQR1XS
MHH-PREB-1 NGLYbIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1m3dGlEPTB;OT6xNkBvVQ>? NWTPUIplW0GQR1XS
DU-4475 MofpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnPNnNnUUN3ME25MlQ1KG6P MYDTRW5ITVJ?
NCI-H1666 M2faV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHfMTpNKSzVyPUmuO|Ehdk1? NU\JcnpUW0GQR1XS
CAMA-1 M3vj[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTlwODDuUS=> M1fKc3NCVkeHUh?=
TYK-nu NFvKNnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LTemlEPTB;OT65OEBvVQ>? MmDyV2FPT0WU
MFE-280 Mn7XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTjUJdKSzVyPUmuPVkhdk1? NFfHNGpUSU6JRWK=
A549 M{jKXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\1bGlEPTB;MUCuNVQhdk1? MlzIV2FPT0WU
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NCI-H82 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnSTWM2OD1{LkmwN|Y6KM7:TR?= Mmj2V2FPT0WU
JVM-2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHiTWM2OD1|LkCzNVg5KM7:TR?= NG\CfoxUSU6JRWK=
SW1116 M{fRdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXm[JRHUUN3ME2zMlA2PDFzIN88US=> NHHkVmFUSU6JRWK=
MDA-MB-453 NYe3e2VpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnPWpAyUUN3ME2zMlExPDN7IN88US=> NWTxRY9JW0GQR1XS
Calu-6 NWnISWNTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfWUWdKSzVyPUOuNVk6PyEQvF2= MUfTRW5ITVJ?
SHP-77 NWL6SYc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTNwNUK4JO69VQ>? M{DVWHNCVkeHUh?=
Capan-2 NY\1[FM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkLqTWM2OD12LkOyOVgyKM7:TR?= MlvzV2FPT0WU
SW948 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NET0WWpKSzVyPUSuO|Q4PzlizszN MoD0V2FPT0WU
HDLM-2 NHTnNWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlf0TWM2OD13LkC3O|I2KM7:TR?= MW\TRW5ITVJ?
LAN-6 NU\MNIdmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1XmN2lEPTB;Nj6yNVQ6PSEQvF2= MnjvV2FPT0WU
LU-135 M3[3NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvHTWM2OD14LkSzNFc4KM7:TR?= MWDTRW5ITVJ?
T84 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTZwOUi2OEDPxE1? MmXvV2FPT0WU
CAPAN-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3HpfmlEPTB;Nz62NlI{OyEQvF2= MlvuV2FPT0WU
SW1417 NHnKeVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHHUG5KSzVyPUeuPVE4OzFizszN NGniWW5USU6JRWK=
BALL-1 NFzmTZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrNTWM2OD16LkWwOFA6KM7:TR?= NHzmZoFUSU6JRWK=
HT-29 NF3nRpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTFe2tTUUN3ME25MlA4PTl7IN88US=> MX\TRW5ITVJ?
C3A NFfRVnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;hNGlEPTB;OT64PFM6PCEQvF2= NVrhcJptW0GQR1XS
NCI-H1993 NFrFR3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\DTWM2OD1zMD61NFgyKM7:TR?= MofIV2FPT0WU
SK-MEL-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIizc3VKSzVyPUGxMlYzQDlizszN M2rjZXNCVkeHUh?=
DU-145 M4LyZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX\JR|UxRTF2LkWwOVIh|ryP MofvV2FPT0WU
KP-N-YN NYPLb2tsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDmWXRpUUN3ME2xOE42OTB|IN88US=> MXzTRW5ITVJ?
CCRF-CEM MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkT4TWM2OD1zND63PFA6KM7:TR?= M4r4XXNCVkeHUh?=
ZR-75-30 M3myR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWS5SYhKUUN3ME2xOk4{OzB|IN88US=> M2ftXnNCVkeHUh?=
A673 MlHZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4nPdmlEPTB;MkCuOVUxPyEQvF2= Ml72V2FPT0WU
K-562 M{CzVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYPsSIVyUUN3ME2yPE41OTh|IN88US=> Mmf6V2FPT0WU

... 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
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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
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  • 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
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  • 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 (38.33 mM) warming
DMSO 0.01 mg/mL (0.02 mM)
Water <1 mg/mL
In vivo NMP+polyethylene glycol 300 (10+90, v+v) 30 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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
in solvent
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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    C2
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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

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
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    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

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

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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
NCT01634061 Completed Castration-resistant Prostate Cancer Novartis Pharmaceuticals|Novartis September 2012 Phase 1

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.

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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.

PI3K Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID