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 84 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.

    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.

  • 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.

    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.

  • 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.

  • (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 M1[2Z2FvfGmvaXPyc4Jq[WxiQYPzZZk> Mlr3NVghcA>? MWTEUXNQ NVrkZXNISW62aYTyfZBidm:|b33hcEBi[3Srdnn0fUB4cXSqIFXDOVAhd2ZiMD6wNFI2KM7:TR?= MYqyOFgxPTl2Nh?=
MCF7 MlvxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3f2elAvODFvMUCwJO69VQ>? NU\xc4o1PDhiaB?= NHLmXG9FVVOR MmTSTWM2OD1yLkezJO69VQ>? MVSyN|g4OTlyNB?=
HCT116 M3OwZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvYO3AxNjBzLUGwNEDPxE1? NIn6VGc1QCCq Mm\RSG1UVw>? NX7LVZNHUUN3ME2xMlE3KM7:TR?= NX\M[3R7OjN6N{G5NFQ>
U87MG NWfkXHdDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVOwMlAyNTFyMDFOwG0> MXS0PEBp NXrhWmZnTE2VTx?= MVXJR|UxRTFwM{Kg{txO NVWzO5BrOjN6N{G5NFQ>
HBC4 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\pfGsxNjBzLUGwNEDPxE1? NWLq[|lTPDhiaB?= NF\qcWhNd2diR1m1NF0uQC54MTDN NYLLSlRkOjJ|M{[yOFY>
BSY1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoT4NE4xOS1zMECg{txO MUO0PEBp M1zifWxw\yCJSUWwQU05NjR6IF2= MWiyNlM{PjJ2Nh?=
HBC5 MmXJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX3GPJdbOC5yMT2xNFAh|ryP M3PjdVQ5KGh? Ml3TUI9oKEeLNUC9MVcvQDdiTR?= NFrDOoszOjN|NkK0Oi=>
MCF7 NXTYcmd1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGj1XmMxNjBzLUGwNEDPxE1? NV7pOVdUPDhiaB?= NXzzepd4VG:pIFfJOVA:NThwMU[gUS=> MX6yNlM{PjJ2Nh?=
MDA-MB-231 M4TvT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvpOIhXOC5yMT2xNFAh|ryP MmDWOFghcA>? MkHUUI9oKEeLNUC9MVgvODliTR?= NYDwTm52OjJ|M{[yOFY>
U251 NVH5NFdoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4iwTlAvODFvMUCwJO69VQ>? NV;OTWV{PDhiaB?= MlvjUI9oKEeLNUC9MVcvPjZiTR?= M3nEcVIzOzN4MkS2
SF268 NV\mVphyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13BRVAvODFvMUCwJO69VQ>? MUC0PEBp M{HHcGxw\yCJSUWwQU04Njl{IF2= M2rrO|IzOzN4MkS2
SF295 NY\NSlJpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLZNFExNjBzLUGwNEDPxE1? MUm0PEBp MUPMc4chT0l3ME2tPE4{OSCP M3TkblIzOzN4MkS2
SF539 MlOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PHTVAvODFvMUCwJO69VQ>? Mn;HOFghcA>? MomyUI9oKEeLNUC9MVgvPTliTR?= MXGyNlM{PjJ2Nh?=
SNB75 NXi5e41wT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHWwXm0xNjBzLUGwNEDPxE1? MnPNOFghcA>? NHTxWZFNd2diR1m1NF0uQC53ODDN NVPKXpJVOjJ|M{[yOFY>
SNB78 NF;mbFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX7rTZQ{OC5yMT2xNFAh|ryP NHLNZ3k1QCCq NUK0PFA2VG:pIFfJOVA:NThwNkWgUS=> M1G0c|IzOzN4MkS2
HCC2998 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYCwMlAyNTFyMDFOwG0> NXmzW5RZPDhiaB?= M17ESmxw\yCJSUWwQU05NjB3IF2= NHzrcXUzOjN|NkK0Oi=>
KM12 NU\w[XhOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrZNE4xOS1zMECg{txO NULzNnBpPDhiaB?= MnLzUI9oKEeLNUC9MVcvPTRiTR?= MkHzNlI{OzZ{NE[=
HT-29 Mn7CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{Hu[|AvODFvMUCwJO69VQ>? NF3GV4o1QCCq NWDzNFNIVG:pIFfJOVA:NTdwN{WgUS=> MUeyNlM{PjJ2Nh?=
HCT15 Ml7TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWiwMlAyNTFyMDFOwG0> MW[0PEBp NGPFNHpNd2diR1m1NF0uQC5yMzDN NH:2dIQzOjN|NkK0Oi=>
HCT116 NXn6XXc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXSwMlAyNTFyMDFOwG0> NH3USY41QCCq MX7Mc4chT0l3ME2tO{43OSCP M4PtZVIzOzN4MkS2
NCI-H23 M4POTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWmwMlAyNTFyMDFOwG0> NIX2WFA1QCCq M33DZWxw\yCJSUWwQU04NjZ2IF2= MXGyNlM{PjJ2Nh?=
NCI-H226 NVf1fZM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jCRVAvODFvMUCwJO69VQ>? NEWyWZE1QCCq NGXDRnRNd2diR1m1NF0uQC52NDDN NVO4TmFGOjJ|M{[yOFY>
NCI-H522 M{S1XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PoR|AvODFvMUCwJO69VQ>? M2\0fFQ5KGh? MnnrUI9oKEeLNUC9MVgvPDViTR?= MkDoNlI{OzZ{NE[=
NCI-H438 M{SxcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{HGXlAvODFvMUCwJO69VQ>? NHrjeZU1QCCq MmHwUI9oKEeLNUC9MVgvOTFiTR?= M1rtZ|IzOzN4MkS2
A549 M3nCRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jKVVAvODFvMUCwJO69VQ>? MmPjOFghcA>? NWH3T291VG:pIFfJOVA:NThwMEegUS=> NETNOGUzOjN|NkK0Oi=>
DMS273 NX;kNXNKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLae3VYOC5yMT2xNFAh|ryP MVi0PEBp M4f4[mxw\yCJSUWwQU04NjhyIF2= MXWyNlM{PjJ2Nh?=
DMS114 NFHiU4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnu5NE4xOS1zMECg{txO NVq4fHl6PDhiaB?= MnS5UI9oKEeLNUC9MVgvOzliTR?= MofJNlI{OzZ{NE[=
LOXIMVI M{L0[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfWW5YxNjBzLUGwNEDPxE1? NHvObIw1QCCq NGLQSXRNd2diR1m1NF0uQC54NjDN NXXCZZA{OjJ|M{[yOFY>
OVCAR3 M2LuW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;lO|AvODFvMUCwJO69VQ>? MYG0PEBp MoexUI9oKEeLNUC9MVgvOTdiTR?= M4jVeFIzOzN4MkS2
OVCAR4 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3P6RlAvODFvMUCwJO69VQ>? NWX4[GpsPDhiaB?= MmXUUI9oKEeLNUC9MVgvPThiTR?= NYrRdplyOjJ|M{[yOFY>
OVCAR5 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGX6ZpgxNjBzLUGwNEDPxE1? M2rXWFQ5KGh? M3m4bGxw\yCJSUWwQU04NjV5IF2= MnLtNlI{OzZ{NE[=
OVCAR8 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDrRYIxNjBzLUGwNEDPxE1? NELaO2Y1QCCq MWrMc4chT0l3ME2tO{45PCCP M16yN|IzOzN4MkS2
SKOV3 MlH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2DSN|AvODFvMUCwJO69VQ>? NWPkZo5IPDhiaB?= NWrORlhrVG:pIFfJOVA:NThwNEGgUS=> NYS0WJlbOjJ|M{[yOFY>
RXF631L MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrrZXcxNjBzLUGwNEDPxE1? Mn;COFghcA>? M3XROGxw\yCJSUWwQU05NjJzIF2= NFz1cYszOjN|NkK0Oi=>
ACHN NH7yPIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHKNE4xOS1zMECg{txO M1vYclQ5KGh? MWjMc4chT0l3ME2tO{46PSCP M3zHVVIzOzN4MkS2
St-4 M2fTc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUmwMlAyNTFyMDFOwG0> M1HBVFQ5KGh? MmXzUI9oKEeLNUC9MVcvPDdiTR?= NH6xb5gzOjN|NkK0Oi=>
MKN1 NGi1RmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7iNGQxNjBzLUGwNEDPxE1? NXKxO|VyPDhiaB?= MXPMc4chT0l3ME2tPE41OSCP MX2yNlM{PjJ2Nh?=
MKN7 NV\KfZB2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\oOlAvODFvMUCwJO69VQ>? MoL4OFghcA>? MWrMc4chT0l3ME2tO{43QCCP MoDGNlI{OzZ{NE[=
MKN28 NH\IbYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjMfJRUOC5yMT2xNFAh|ryP MmfSOFghcA>? NXfrZng1VG:pIFfJOVA:NTdwMEegUS=> NYeyUXFkOjJ|M{[yOFY>
MKN45 M2\3XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnPBNE4xOS1zMECg{txO MmmwOFghcA>? M373Tmxw\yCJSUWwQU05NjN2IF2= MUOyNlM{PjJ2Nh?=
MKN74 NYXDR5ZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrpNE4xOS1zMECg{txO MVy0PEBp NF3xT|VNd2diR1m1NF0uPy52MjDN MkTjNlI{OzZ{NE[=
DU145 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWj5NZYzOC5yMT2xNFAh|ryP MWS0PEBp M{m1dmxw\yCJSUWwQU05NjF4IF2= MmPhNlI{OzZ{NE[=
PC3 NGD5OJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmX6NE4xOS1zMECg{txO MUO0PEBp M{fRTmxw\yCJSUWwQU05NjZ4IF2= Ml;zNlI{OzZ{NE[=
Trypanosoma brucei brucei MVLGeY5kfGmxbjDBd5NigQ>? NHzOWHIzODBibl2= NXLPN3J{OTJiaB?= NWTYXFRTTE2VTx?= NUfRVIpbTGWlcnXhd4UhcW5icHjvd5Bpd3SrZInsJIlvd3OrdH;sJJBpd3OyaHH0[UBt\X[nbB?= MY[yOFgxPTl2Nh?=
Trypanosoma brucei brucei M2nXV2Z2dmO2aX;uJGF{e2G7 NGjQT4cyQCCq Mn6xSG1UVw>? M4Tod2lvcGmkaYTpc44hd2ZicnXj[ZB1d3JvbXXkbYF1\WRiZX7kc4N6fG:|aYOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5idILhcpNn\XK{aX6geZB1[Wun NF3JfoEzPDhyNUm0Oi=>
Trypanosoma brucei brucei MYTGeY5kfGmxbjDBd5NigQ>? MmnGNlAxKG6P MWKxNkBp M4XnVWROW09? NUDFTmttTW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? M1XBO|I1QDB3OUS2
Trypanosoma brucei brucei M1mxSGZ2dmO2aX;uJGF{e2G7 MYWyNFAhdk1? MVOxNkBp NYLXO4J1TE2VTx?= MXjF[oZm[3Rib36gdIhwe3CqYYTp[Jlt[2ixbHnu[UBt\X[nbB?= NVPuN|BNOjR6MEW5OFY>
UM-UC-3 MkCxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfQWHBoUUN3ME2zNVUheE1? MUPTRW5ITVJ?
SBC-1 MnnOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2r3cGlEPTB;N{SyJJBO MWTTRW5ITVJ?
MKN1 NWHWVZdGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWjJR|UxRTJwODDuUS=> NFzZVWhUSU6JRWK=
NCI-H720 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVzJR|UxRTNwNUegcm0> NUPDc4U1W0GQR1XS
BFTC-909 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mlm4TWM2OD1|LkexJI5O Mm\jV2FPT0WU
BPH-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2i4bGlEPTB;ND63OkBvVQ>? Ml:2V2FPT0WU
PC-3 NEfQUVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTVwMEmgcm0> M2[1fnNCVkeHUh?=
AN3-CA NXLXTXNFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH:2Nm9KSzVyPUWuOVYhdk1? NUDERpJlW0GQR1XS
HN NFX3RmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTVwOU[gcm0> MmLKV2FPT0WU
HCC2218 M1fWN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1KwfmlEPTB;Nj62NUBvVQ>? Moj2V2FPT0WU
KP-4 M3jHXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnkTWM2OD15IH7N Mo\jV2FPT0WU
LU-139 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX:4eJZOUUN3ME23Mlc4KG6P NXzpbHdJW0GQR1XS
ETK-1 NHKzTYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLrTWM2OD15Lki4JI5O MYrTRW5ITVJ?
Ramos-2G6-4C10 NFLFe4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRThwNEmgcm0> NF:0fmZUSU6JRWK=
MHH-PREB-1 NWfPXmFqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\4emlEPTB;OT6xNkBvVQ>? Mn;EV2FPT0WU
DU-4475 NVfpcoV[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPaTWM2OD17LkS0JI5O NHXVOGtUSU6JRWK=
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769-P Ml7BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\aNlhKSzVyPUGwMlQ1KG6P NFvKTVlUSU6JRWK=
L-363 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NITRPXVKSzVyPUGwMlY6KG6P NFLrVWlUSU6JRWK=
ES8 NGO4U|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;H[49KSzVyPUGwMlkhdk1? NU\ESY54W0GQR1XS
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Mewo M3qzZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HtbGlEPTB;MUGuPVkhdk1? MmPjV2FPT0WU
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H4 NYfo[VlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTF{Lk[3JI5O MVPTRW5ITVJ?
BB65-RCC NWG5ZmhET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rBZWlEPTB;MUKuO|Ihdk1? M3f1d3NCVkeHUh?=
NCI-H1793 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnSxTWM2OD1zMj64NkBvVQ>? NEH6O2hUSU6JRWK=
KARPAS-45 NHG2UXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLRdI1KSzVyPUGzMlUyKG6P NYPo[GFWW0GQR1XS
GCT NHmxbHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLhTWM2OD1zMz62PEBvVQ>? MVPTRW5ITVJ?
EoL-1 NHvWVZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\ETWM2OD1zMz65N{BvVQ>? M3HZcXNCVkeHUh?=
LB2241-RCC MofRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIqzbnFKSzVyPUG0MlAyKG6P NYTZ[lE5W0GQR1XS
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LOXIMVI MmrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrSfXZUUUN3ME2xOE46QSCwTR?= M4X0[HNCVkeHUh?=
COR-L105 NYnGfYx7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTF3LkC0JI5O NXfRSZRlW0GQR1XS
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VMRC-RCZ NIC0[ZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTF3Lk[zJI5O MX3TRW5ITVJ?
HH NUi5bG1pT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LmfGlEPTB;MUWuO{BvVQ>? NGHIbmNUSU6JRWK=
NUGC-3 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjKblRMUUN3ME2xOk4{PCCwTR?= MYfTRW5ITVJ?
EGI-1 M2LkUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfaOlNKSzVyPUG2MlQ{KG6P M1\0T3NCVkeHUh?=
OS-RC-2 NXXQfIJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PWUGlEPTB;MU[uOFchdk1? NWTSdJo5W0GQR1XS
MOLT-16 MlTiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\BeohKSzVyPUG3MlE2KG6P NV7ad2pVW0GQR1XS
NCI-H209 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2q4OGlEPTB;MUeuNlkhdk1? MWfTRW5ITVJ?
697 NXzwcIdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV7oPFZGUUN3ME2xO{41OyCwTR?= NXzGcldzW0GQR1XS
D-56MG NICxeZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3j5R2lEPTB;MUeuOlkhdk1? NFv3S3pUSU6JRWK=
VA-ES-BJ MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvwN4Q4UUN3ME2xO{45OyCwTR?= MYPTRW5ITVJ?
EW-16 M3TjdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH3rN41KSzVyPUG4MlA1KG6P M3T1OnNCVkeHUh?=
HGC-27 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPpTWM2OD1zOD6wOkBvVQ>? M1XmN3NCVkeHUh?=
ES7 M1XMWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{LITWlEPTB;MUiuNFkhdk1? M1v5fnNCVkeHUh?=
HuH-7 M3nxUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\wS4VKSzVyPUG4MlQhdk1? M13Xd3NCVkeHUh?=
BCPAP NYLCTldtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTEcXNKSzVyPUG4MlY2KG6P NV7pVFlyW0GQR1XS
SW1710 MmjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PBOWlEPTB;MUiuO|Ihdk1? MYPTRW5ITVJ?
IST-MEL1 NHG2S5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTF6Lke3JI5O Mln0V2FPT0WU
SF295 NIfFXYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTF6LkmzJI5O MW\TRW5ITVJ?
RPMI-7951 M3rKdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2[zUGlEPTB;MUmuNlghdk1? M2r3fXNCVkeHUh?=
SF126 NWq5UZRbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjqR4I{UUN3ME2xPU41OSCwTR?= MnHDV2FPT0WU
GAMG NV62NHNOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVT0d2dDUUN3ME2xPU41QCCwTR?= M1HPZ3NCVkeHUh?=
KNS-81-FD NHHs[HlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHUdFBKSzVyPUG5MlU1KG6P NH\hWHhUSU6JRWK=
RT-112 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTF7Lk[2JI5O NWfqNFA5W0GQR1XS
DEL MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTJyLkS5JI5O MYjTRW5ITVJ?
CGTH-W-1 M{GweGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPu[5ZKSzVyPUKwMlY{KG6P M1LsWHNCVkeHUh?=
HOS MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3HQRWlEPTB;MkGuNFYhdk1? NEfo[IFUSU6JRWK=
ES4 MmK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\tS3RNUUN3ME2yNU4xQCCwTR?= M1XTdXNCVkeHUh?=
RXF393 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUPweI9rUUN3ME2yNU41PSCwTR?= M1;LS3NCVkeHUh?=
NCI-H2030 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrhTWM2OD1{MT61NkBvVQ>? NEfVd5NUSU6JRWK=
YH-13 NGOxeG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVLJR|UxRTJzLki4JI5O NEnyXG5USU6JRWK=
HT-1080 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJzLkmzJI5O NVLLbYdFW0GQR1XS
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786-0 M4r5e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTJ{LkK5JI5O M3TheHNCVkeHUh?=
ME-180 M1nlfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTN[ZJLUUN3ME2yNk41OyCwTR?= M{S4VnNCVkeHUh?=
NB69 NV3DfGlET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnmVVZtUUN3ME2yNk42OyCwTR?= NED2dXNUSU6JRWK=
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TGBC1TKB MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTrTIMxUUN3ME2yN{4xPSCwTR?= MXTTRW5ITVJ?
SW780 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3q4[GlEPTB;MkOuNVMhdk1? NXi3TohNW0GQR1XS
MG-63 NH;zNHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnTyTWM2OD1{Mz60OUBvVQ>? NYjhU|NTW0GQR1XS
BV-173 M1fZd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTJ|Lki3JI5O MXzTRW5ITVJ?
CAL-51 MoTCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnzbmtyUUN3ME2yN{45QSCwTR?= NITuXnhUSU6JRWK=
A375 M3nmdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzHTpVKSzVyPUKzMlk{KG6P M3PJRnNCVkeHUh?=
MEL-HO MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{O2OGlEPTB;MkSuNFQhdk1? M{LvTHNCVkeHUh?=
EFO-27 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NISxVXBKSzVyPUK0MlM{KG6P MUDTRW5ITVJ?
Hs-578-T Ml;SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\WTWM2OD1{ND61PEBvVQ>? NFHyVYVUSU6JRWK=
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CTB-1 M3yzemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvYUJJ4UUN3ME2yOE43PyCwTR?= M1v0bXNCVkeHUh?=
FTC-133 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TTb2lEPTB;MkWuNUBvVQ>? NW\5doJUW0GQR1XS
MOLT-4 Ml\oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fTdmlEPTB;MkWuNVIhdk1? MUjTRW5ITVJ?
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ES3 NWLHVFhzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1;ZZmlEPTB;MkWuNlIhdk1? MUjTRW5ITVJ?
TI-73 NYr5XJlPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkSxTWM2OD1{NT6yPEBvVQ>? MVHTRW5ITVJ?
MPP-89 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVnJR|UxRTJ3LkOyJI5O Mnv3V2FPT0WU
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LXF-289 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfJOGlKSzVyPUK2MlA1KG6P M2jVdXNCVkeHUh?=
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HOP-92 Mk\TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzSVFZKSzVyPUK2MlQ5KG6P MoDKV2FPT0WU
HuO9 NHHsUphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3raOWlEPTB;Mk[uO|Yhdk1? MlHXV2FPT0WU
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RS4-11 NXjZWXQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjl[5k4UUN3ME2yOk46OSCwTR?= M{DpSXNCVkeHUh?=
NCI-H292 NXziNWZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHqTWM2OD1{NzDuUS=> M3PNVHNCVkeHUh?=
DB NHnW[49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrlTWM2OD1{Nz6zOkBvVQ>? MlnUV2FPT0WU
SW1088 M2fnUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmLqTWM2OD1{OD6yPUBvVQ>? M{npUXNCVkeHUh?=
A204 M{ezVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmS4TWM2OD1{OD60O{BvVQ>? MUHTRW5ITVJ?
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ONS-76 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LCWGlEPTB;MkmuNFUhdk1? NITsTG1USU6JRWK=
D-263MG MmjDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTJ7LkO1JI5O NVzqdWZTW0GQR1XS
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BHT-101 MnXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTNyLkC1JI5O M4rGSXNCVkeHUh?=
NOS-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXDdpVTUUN3ME2zNE4yOiCwTR?= NVXrZ21ZW0GQR1XS
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QIMR-WIL MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fQVWlEPTB;M{CuOkBvVQ>? MkTZV2FPT0WU
JVM-3 NFnaUXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLRTWM2OD1|MD64N{BvVQ>? NHPLVIhUSU6JRWK=
KU-19-19 NWDjZYxwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTNzLkGzJI5O NILj[o9USU6JRWK=
OVCAR-8 NVPGcWpTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nkOWlEPTB;M{GuNlYhdk1? Mn3nV2FPT0WU
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EW-18 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLhTWM2OD1|MT64OkBvVQ>? NEK1b3RUSU6JRWK=
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COLO-800 NV7qOZFGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;ZVmlEPTB;M{KuPVIhdk1? NHzoNWRUSU6JRWK=
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COLO-684 M4O4e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrrNFVYUUN3ME2zN{42QCCwTR?= NV[zVIxyW0GQR1XS
RPMI-8226 MofGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFG3To9KSzVyPUOzMlgzKG6P MmnHV2FPT0WU
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Becker MmPtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3fNXWlEPTB;M{SuNlEhdk1? MXHTRW5ITVJ?
NCI-H28 MlHzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjzTWtKSzVyPUO0MlQ1KG6P M4LueHNCVkeHUh?=
CAL-120 M1LCe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\CcY5SUUN3ME2zOE44OiCwTR?= MYDTRW5ITVJ?
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OVCAR-5 NID4Vo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3KwTGlEPTB;M{WuOFchdk1? M{TRfHNCVkeHUh?=
LAMA-84 M{K4bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLiTWM2OD1|NT64O{BvVQ>? M{XKOnNCVkeHUh?=
CAKI-1 NYnvc|ZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jtZ2lEPTB;M{[uOFMhdk1? M2r0OHNCVkeHUh?=
Daoy NHj1eI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPHTWM2OD1|Nj63JI5O NXvSemIyW0GQR1XS
CAL-62 NYTQSYFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWD4eW42UUN3ME2zOk45PiCwTR?= M4PKZ3NCVkeHUh?=
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NCI-H358 M3\kUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTFwOUW1NFMh|ryP M4TifHNCVkeHUh?=
OAW-28 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4qz[GlEPTB;Mj6wOlkyQSEQvF2= NVrGWVJlW0GQR1XS
C8166 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTs[m86UUN3ME2yMlY{Ozl{IN88US=> NVrFeXdzW0GQR1XS
COLO-678 M{m5T2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHYU2ZKSzVyPUKuPFM4PjhizszN NGXMZoxUSU6JRWK=
SK-N-DZ M{ToVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTJwOE[zPFEh|ryP MYfTRW5ITVJ?
NCI-H82 NVPtUYxGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MojQTWM2OD1{LkmwN|Y6KM7:TR?= MofOV2FPT0WU
JVM-2 NXP2epZwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LUeGlEPTB;Mz6wN|E5QCEQvF2= Ml35V2FPT0WU
SW1116 NX3uS|dLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIfKbGpKSzVyPUOuNFU1OTFizszN M3HoTXNCVkeHUh?=
MDA-MB-453 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTNwMUC0N|kh|ryP M3;PZXNCVkeHUh?=
Calu-6 MlvUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX[1ZowzUUN3ME2zMlE6QTdizszN NFO5So9USU6JRWK=
SHP-77 M{L6b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjJUINKSzVyPUOuOVI5KM7:TR?= NVvqclRMW0GQR1XS
Capan-2 M{DjZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrhPWxjUUN3ME20MlMzPThzIN88US=> M1jlWXNCVkeHUh?=
SW948 M{XmTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml7ZTWM2OD12Lke0O|c6KM7:TR?= NIHiXWRUSU6JRWK=
HDLM-2 NEDsVWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPmW2hKSzVyPUWuNFc4OjVizszN M{TWeXNCVkeHUh?=
LAN-6 NV\6bo12T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PPdWlEPTB;Nj6yNVQ6PSEQvF2= M4\BeHNCVkeHUh?=
LU-135 MoXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXsXYZKSzVyPU[uOFMxPzdizszN NEnhVmtUSU6JRWK=
T84 M1LyZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPHTWM2OD14Lkm4OlQh|ryP MnzEV2FPT0WU
CAPAN-1 NW[yOlg{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTdwNkKyN|Mh|ryP MVXTRW5ITVJ?
SW1417 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfUTWM2OD15LkmxO|MyKM7:TR?= M1zOS3NCVkeHUh?=
BALL-1 M1nZSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnv3TWM2OD16LkWwOFA6KM7:TR?= NIH6T4pUSU6JRWK=
HT-29 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTlwMEe1PVkh|ryP NW\SV|NNW0GQR1XS
C3A NGXSe4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIO5S2ZKSzVyPUmuPFg{QTRizszN MULTRW5ITVJ?
NCI-H1993 Mn71S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHKXYtKSzVyPUGwMlUxQDFizszN M37aO3NCVkeHUh?=
SK-MEL-1 M{jke2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXQR3FWUUN3ME2xNU43Ojh7IN88US=> NFjHdHZUSU6JRWK=
DU-145 M3LyeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHO3Wm5KSzVyPUG0MlUxPTJizszN Mmq4V2FPT0WU
KP-N-YN MnO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPmdmdKSzVyPUG0MlUyODNizszN NUfyeph2W0GQR1XS
CCRF-CEM M4WxbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTF2Lke4NFkh|ryP NEXH[IRUSU6JRWK=
ZR-75-30 M2TrVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH[wXllKSzVyPUG2MlM{ODNizszN NH\6XYtUSU6JRWK=
A673 NEnGOGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHOTWM2OD1{MD61OVA4KM7:TR?= NXfjbVdbW0GQR1XS
K-562 NF3iZoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTXTWM2OD1{OD60NVg{KM7:TR?= NXzFOFRWW0GQR1XS

... 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 to the product individually and in order(Data is from Selleck tests instead of citations):
NMP+polyethylene glycol 300 (10+90, v+v)
For best results, use promptly after mixing. 		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
in solvent
Synonyms N/A

Bio Calculators

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01717898 Terminated Castrate-resistant Prostate Cancer Charles Ryan|Novartis Pharmaceuticals|University of California San Francisco January 31 2013 Phase 1|Phase 2
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
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.

selleck catalog

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID