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 81 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. 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.

     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

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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 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 MWDBcpRqdWmlcn;ibYFtKEG|c3H5 MlTXNVghcA>? NUfWWIRsTE2VTx?= MoD4RY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? NFXZW5gzPDhyNUm0Oi=>
MCF7 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTTVZJXOC5yMT2xNFAh|ryP MYm0PEBp M4jtcGROW09? NHzuUVJKSzVyPUCuO|Mh|ryP MYqyN|g4OTlyNB?=
HCT116 NHPKNWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTZNE4xOS1zMECg{txO NYLBeVNvPDhiaB?= Mmn2SG1UVw>? NIPRSI5KSzVyPUGuNVYh|ryP NYD3UIVVOjN6N{G5NFQ>
U87MG NUDl[mduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\oNE4xOS1zMECg{txO MYW0PEBp NFm2cWdFVVOR NWHTVmlpUUN3ME2xMlMzKM7:TR?= M4PNVlI{QDdzOUC0
HBC4 NVW3TXV7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXSwMlAyNTFyMDFOwG0> MVO0PEBp NGO5WIdNd2diR1m1NF0uQC54MTDN NV;tV2c1OjJ|M{[yOFY>
BSY1 NYnGNYw4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYrVbpBnOC5yMT2xNFAh|ryP MnnqOFghcA>? MkLaUI9oKEeLNUC9MVgvPDhiTR?= Ml;tNlI{OzZ{NE[=
HBC5 Ml3QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlT4NE4xOS1zMECg{txO NGO5cos1QCCq NWO2U2E1VG:pIFfJOVA:NTdwOEegUS=> MUiyNlM{PjJ2Nh?=
MCF7 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4TNPFAvODFvMUCwJO69VQ>? M4PpblQ5KGh? NYTFU3VMVG:pIFfJOVA:NThwMU[gUS=> MlTVNlI{OzZ{NE[=
MDA-MB-231 NYnHflhlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3Me|dtOC5yMT2xNFAh|ryP MnvQOFghcA>? NIP6dYtNd2diR1m1NF0uQC5yOTDN NFjuWIIzOjN|NkK0Oi=>
U251 NVH6WHJXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonxNE4xOS1zMECg{txO NUTvUXJuPDhiaB?= NYOyco1PVG:pIFfJOVA:NTdwNk[gUS=> NH\ZO4YzOjN|NkK0Oi=>
SF268 Mk\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPyNE4xOS1zMECg{txO NHvKWos1QCCq NF3yU4pNd2diR1m1NF0uPy57MjDN Mn76NlI{OzZ{NE[=
SF295 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHrRbVgxNjBzLUGwNEDPxE1? NEDGfIQ1QCCq NIrZXIhNd2diR1m1NF0uQC5|MTDN M1\3XVIzOzN4MkS2
SF539 NGfpeWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVmwMlAyNTFyMDFOwG0> M2HtfVQ5KGh? NXnIR3VPVG:pIFfJOVA:NThwNUmgUS=> NG\ibWUzOjN|NkK0Oi=>
SNB75 M{f5WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTFNE4xOS1zMECg{txO NWnxWlY3PDhiaB?= NGXk[JdNd2diR1m1NF0uQC53ODDN NYT6XoM1OjJ|M{[yOFY>
SNB78 NWXkRnNDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;NRmllOC5yMT2xNFAh|ryP M3\5flQ5KGh? M2DGUmxw\yCJSUWwQU05NjZ3IF2= NVzVXopxOjJ|M{[yOFY>
HCC2998 NUDXcXZXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFPQRZAxNjBzLUGwNEDPxE1? NXnQO3VjPDhiaB?= MUfMc4chT0l3ME2tPE4xPSCP NV2y[5VkOjJ|M{[yOFY>
KM12 M376Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzCNE4xOS1zMECg{txO M3LCZlQ5KGh? NIrjN5FNd2diR1m1NF0uPy53NDDN NFS0fowzOjN|NkK0Oi=>
HT-29 NEi0R2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLyU3UxNjBzLUGwNEDPxE1? NXy5U3hlPDhiaB?= M4X0fWxw\yCJSUWwQU04Njd3IF2= MkjGNlI{OzZ{NE[=
HCT15 MoX1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofFNE4xOS1zMECg{txO NWTYcXJzPDhiaB?= NHrUfpRNd2diR1m1NF0uQC5yMzDN NEHkRpMzOjN|NkK0Oi=>
HCT116 NXL4O2QyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3HHVFAvODFvMUCwJO69VQ>? NGr5UHM1QCCq M3vqWmxw\yCJSUWwQU04NjZzIF2= M2G0cFIzOzN4MkS2
NCI-H23 MkTvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWOwMlAyNTFyMDFOwG0> MUW0PEBp M13YNWxw\yCJSUWwQU04NjZ2IF2= NIHTZpQzOjN|NkK0Oi=>
NCI-H226 NXn3XVlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13TN|AvODFvMUCwJO69VQ>? M37NcVQ5KGh? NUXMdYpbVG:pIFfJOVA:NThwNESgUS=> NEKxOmMzOjN|NkK0Oi=>
NCI-H522 MnXvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3hNE4xOS1zMECg{txO M4HrO|Q5KGh? NUDmbZZSVG:pIFfJOVA:NThwNEWgUS=> NWO3b4dpOjJ|M{[yOFY>
NCI-H438 Mn22S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH:ybGYxNjBzLUGwNEDPxE1? MVy0PEBp MlvxUI9oKEeLNUC9MVgvOTFiTR?= MWCyNlM{PjJ2Nh?=
A549 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF7DVVkxNjBzLUGwNEDPxE1? M3;nRVQ5KGh? NVzSRox[VG:pIFfJOVA:NThwMEegUS=> MoXVNlI{OzZ{NE[=
DMS273 M2PnXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXpVYsxNjBzLUGwNEDPxE1? M{XsdVQ5KGh? NFXa[VFNd2diR1m1NF0uPy56MDDN MmfmNlI{OzZ{NE[=
DMS114 NHPMeZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTrUm8xNjBzLUGwNEDPxE1? NWP6bFZJPDhiaB?= M3z4dWxw\yCJSUWwQU05NjN7IF2= Mn2xNlI{OzZ{NE[=
LOXIMVI Ml\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHLe3dkOC5yMT2xNFAh|ryP MXq0PEBp NH7sVnRNd2diR1m1NF0uQC54NjDN M1TnO|IzOzN4MkS2
OVCAR3 MoP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;pPIcxNjBzLUGwNEDPxE1? MUW0PEBp M1;Td2xw\yCJSUWwQU05NjF5IF2= MWeyNlM{PjJ2Nh?=
OVCAR4 Mke5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3[zXVAvODFvMUCwJO69VQ>? M1P4bVQ5KGh? M2mxN2xw\yCJSUWwQU05NjV6IF2= NVzpO|ZwOjJ|M{[yOFY>
OVCAR5 NVLmS3RVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVSwMlAyNTFyMDFOwG0> NVXQXnBZPDhiaB?= MXLMc4chT0l3ME2tO{42PyCP NXfHSJpMOjJ|M{[yOFY>
OVCAR8 MnLyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nHb|AvODFvMUCwJO69VQ>? MljlOFghcA>? MkWwUI9oKEeLNUC9MVcvQDRiTR?= MXKyNlM{PjJ2Nh?=
SKOV3 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYCwMlAyNTFyMDFOwG0> M{\1VlQ5KGh? NITDWGZNd2diR1m1NF0uQC52MTDN NEXvTYMzOjN|NkK0Oi=>
RXF631L MlG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIDjTG8xNjBzLUGwNEDPxE1? MYS0PEBp NVvPR5RrVG:pIFfJOVA:NThwMkGgUS=> MkfTNlI{OzZ{NE[=
ACHN NVO1T3B7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvSNE4xOS1zMECg{txO M1LLdVQ5KGh? NIfOXVBNd2diR1m1NF0uPy57NTDN NHG5c40zOjN|NkK0Oi=>
St-4 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13TeFAvODFvMUCwJO69VQ>? NIjUOpQ1QCCq MYrMc4chT0l3ME2tO{41PyCP NHXRN5UzOjN|NkK0Oi=>
MKN1 MlnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV2wMlAyNTFyMDFOwG0> NWTmUJduPDhiaB?= NVnRfZJGVG:pIFfJOVA:NThwNEGgUS=> NX;IdI9yOjJ|M{[yOFY>
MKN7 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnTR485OC5yMT2xNFAh|ryP NGLLepg1QCCq NHfPSpRNd2diR1m1NF0uPy54ODDN NYrqNmxoOjJ|M{[yOFY>
MKN28 NXLPbJhST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnP3NE4xOS1zMECg{txO MVW0PEBp NW[0UXZxVG:pIFfJOVA:NTdwMEegUS=> MUeyNlM{PjJ2Nh?=
MKN45 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEP5NocxNjBzLUGwNEDPxE1? NITCWXc1QCCq NGPJNYxNd2diR1m1NF0uQC5|NDDN M{DPfFIzOzN4MkS2
MKN74 M1nZXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2wMlAyNTFyMDFOwG0> NUC4TohlPDhiaB?= Ml7kUI9oKEeLNUC9MVcvPDJiTR?= M4rQc|IzOzN4MkS2
DU145 NFeyeFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWOwMlAyNTFyMDFOwG0> NVrTUFRQPDhiaB?= Mm\MUI9oKEeLNUC9MVgvOTZiTR?= NHTkW5gzOjN|NkK0Oi=>
PC3 NILVXZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWWwMlAyNTFyMDFOwG0> MoXEOFghcA>? M3v4RWxw\yCJSUWwQU05NjZ4IF2= NXWxfXZ2OjJ|M{[yOFY>
Trypanosoma brucei brucei MnzJSpVv[3Srb36gRZN{[Xl? M{n6S|IxOCCwTR?= NV;0d2d5OTJiaB?= M17XOGROW09? NX3CToRDTGWlcnXhd4UhcW5icHjvd5Bpd3SrZInsJIlvd3OrdH;sJJBpd3OyaHH0[UBt\X[nbB?= MV:yOFgxPTl2Nh?=
Trypanosoma brucei brucei M3TFe2Z2dmO2aX;uJGF{e2G7 NUXSWoVqOThiaB?= NFnOWHpFVVOR NF\ybFZKdmirYnn0bY9vKG:oIILlZ4VxfG:{LX3l[IlifGWmIHXu[I9kgXSxc3nzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIITyZY5{\mW{cnnuJJVxfGGtZR?= MVKyOFgxPTl2Nh?=
Trypanosoma brucei brucei Mk\PSpVv[3Srb36gRZN{[Xl? Mni5NlAxKG6P NXzyNIMzOTJiaB?= M1K0XGROW09? MkWwSYZn\WO2IH;uJJNxcGmwZ3;tfYxmcW5ibHX2[Yw> M{nhN|I1QDB3OUS2
Trypanosoma brucei brucei MoDLSpVv[3Srb36gRZN{[Xl? MU[yNFAhdk1? M2rifVEzKGh? NHPTXmxFVVOR NIC3N3VG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> NXLoXWxlOjR6MEW5OFY>
UM-UC-3 M{XwZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWnJR|UxRTNzNTDwUS=> Mn;QV2FPT0WU
SBC-1 NIqyUXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPpXmtKSzVyPUe0NkBxVQ>? M2nWdXNCVkeHUh?=
MKN1 NYPvfW9RT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DJXWlEPTB;Mj64JI5O M17BW3NCVkeHUh?=
NCI-H720 MnjtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXDTWM2OD1|LkW3JI5O Ml7YV2FPT0WU
BFTC-909 NXzDTFR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\EOow6UUN3ME2zMlcyKG6P NXjrZllqW0GQR1XS
BPH-1 M2nzXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTRwN{[gcm0> NUi2emdvW0GQR1XS
PC-3 NIjW[XpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjuendEUUN3ME21MlA6KG6P M{fGU3NCVkeHUh?=
AN3-CA NWnJNHRDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17PbWlEPTB;NT61OkBvVQ>? NIrvW3FUSU6JRWK=
HN MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DucmlEPTB;NT65OkBvVQ>? Ml3JV2FPT0WU
HCC2218 M1LZb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTQTWM2OD14Lk[xJI5O MYHTRW5ITVJ?
KP-4 M3LLVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITYVIpKSzVyPUegcm0> NIHVSZNUSU6JRWK=
LU-139 Mn60S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWS2UXMzUUN3ME23Mlc4KG6P M1n2bnNCVkeHUh?=
ETK-1 M1P1SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWX1RW9mUUN3ME23Mlg5KG6P NGm1VpFUSU6JRWK=
Ramos-2G6-4C10 NWWzdGl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRThwNEmgcm0> Mn3yV2FPT0WU
MHH-PREB-1 Ml7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTlwMUKgcm0> NH:zTHNUSU6JRWK=
DU-4475 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XI[GlEPTB;OT60OEBvVQ>? NVzNcphiW0GQR1XS
NCI-H1666 NWfGUWJUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\VTWM2OD17LkexJI5O M122NnNCVkeHUh?=
CAMA-1 NHHjRmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIf0NVFKSzVyPUmuPEBvVQ>? M3rlRnNCVkeHUh?=
TYK-nu MkLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPBTWM2OD17Lkm0JI5O NFzLZldUSU6JRWK=
MFE-280 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjJXYRKSzVyPUmuPVkhdk1? NXzwclRHW0GQR1XS
A549 NYLTZpFoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\W[2lEPTB;MUCuNVQhdk1? NWi0c4RkW0GQR1XS
769-P MorrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTFyLkS0JI5O NEPxS29USU6JRWK=
L-363 Ml;0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTFyLk[5JI5O NHy5dIJUSU6JRWK=
ES8 NFy4RYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfpRo5KSzVyPUGwMlkhdk1? MYnTRW5ITVJ?
PA-1 M{nmR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzVbJNKSzVyPUGxMlgzKG6P MVHTRW5ITVJ?
Mewo MnnLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPtTWM2OD1zMT65PUBvVQ>? MmfSV2FPT0WU
HSC-3 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzmWYZEUUN3ME2xNk4zOSCwTR?= NUO1XZVtW0GQR1XS
H4 M1uxWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTF{Lk[3JI5O M1LtPXNCVkeHUh?=
BB65-RCC MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlfXTWM2OD1zMj63NkBvVQ>? NWT5bXJpW0GQR1XS
NCI-H1793 M{HPT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1SybmlEPTB;MUKuPFIhdk1? NYTPSGZkW0GQR1XS
KARPAS-45 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIq1dIlKSzVyPUGzMlUyKG6P NHTHUHZUSU6JRWK=
GCT MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3n6eWlEPTB;MUOuOlghdk1? M1rBd3NCVkeHUh?=
EoL-1 NYXnWpQ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\4TWM2OD1zMz65N{BvVQ>? MlLCV2FPT0WU
LB2241-RCC M{jJXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4XL[WlEPTB;MUSuNFEhdk1? NHPsXZpUSU6JRWK=
ES5 NH:wV|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjOTWM2OD1zND63OEBvVQ>? MlP5V2FPT0WU
LOXIMVI MorxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;UR5ZKSzVyPUG0Mlk6KG6P NFLDfIxUSU6JRWK=
COR-L105 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HocWlEPTB;MUWuNFQhdk1? NEXvN5FUSU6JRWK=
P12-ICHIKAWA NX;XXIpNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\lNWlEPTB;MUWuNUBvVQ>? NFSyNZhUSU6JRWK=
CHL-1 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7kTWM2OD1zNT60OUBvVQ>? Ml7yV2FPT0WU
VMRC-RCZ NVzod|U4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjMc29KSzVyPUG1MlY{KG6P M{jYVXNCVkeHUh?=
HH MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWiwVoE3UUN3ME2xOU44KG6P Ml3IV2FPT0WU
NUGC-3 M3;pd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTF4LkO0JI5O Mn\zV2FPT0WU
EGI-1 MoPpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjkfVRZUUN3ME2xOk41OyCwTR?= MoSzV2FPT0WU
OS-RC-2 MoXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV25cFJ7UUN3ME2xOk41PyCwTR?= MlnXV2FPT0WU
MOLT-16 NEP5[2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXPTWM2OD1zNz6xOUBvVQ>? NXjlbmpGW0GQR1XS
NCI-H209 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnS4TWM2OD1zNz6yPUBvVQ>? NXW5cVNEW0GQR1XS
697 NFHoV2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTF5LkSzJI5O MYHTRW5ITVJ?
D-56MG M4jZe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrBfHh{UUN3ME2xO{43QSCwTR?= Mly3V2FPT0WU
VA-ES-BJ MnvjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTF5LkizJI5O M3vXe3NCVkeHUh?=
EW-16 MlPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTF6LkC0JI5O MWjTRW5ITVJ?
HGC-27 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVfDd2hMUUN3ME2xPE4xPiCwTR?= MnHiV2FPT0WU
ES7 NGO2VGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVyyUZU{UUN3ME2xPE4xQSCwTR?= MYDTRW5ITVJ?
HuH-7 NIWxepZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfBdIVKSzVyPUG4MlQhdk1? MmL1V2FPT0WU
BCPAP Ml7GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfIXHdKSzVyPUG4MlY2KG6P M4S5e3NCVkeHUh?=
SW1710 MmLzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPWeFJKSzVyPUG4MlczKG6P M2TsVXNCVkeHUh?=
IST-MEL1 NIXVR41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fy[2lEPTB;MUiuO|chdk1? NG[1WJRUSU6JRWK=
SF295 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1i5d2lEPTB;MUiuPVMhdk1? MYXTRW5ITVJ?
RPMI-7951 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHzOnBsUUN3ME2xPU4zQCCwTR?= NGruZ41USU6JRWK=
SF126 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG\ZTYdKSzVyPUG5MlQyKG6P MnflV2FPT0WU
GAMG Mn;oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PkTWlEPTB;MUmuOFghdk1? MVjTRW5ITVJ?
KNS-81-FD NIH1b4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3:0R2lEPTB;MUmuOVQhdk1? MXnTRW5ITVJ?
RT-112 MmDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWnJR|UxRTF7Lk[2JI5O NFfU[JVUSU6JRWK=
DEL NEfJNJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXm1eI9oUUN3ME2yNE41QSCwTR?= NYD0UYpkW0GQR1XS
CGTH-W-1 MmTPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3vKbGlEPTB;MkCuOlMhdk1? NVTrdJVoW0GQR1XS
HOS NWflW3d[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfXeJpsUUN3ME2yNU4xPiCwTR?= MlX2V2FPT0WU
ES4 NHHCSY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTJzLkC4JI5O MVfTRW5ITVJ?
RXF393 NF3jNpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTJzLkS1JI5O NHX1RXFUSU6JRWK=
NCI-H2030 MlnDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFi3RXhKSzVyPUKxMlUzKG6P MXnTRW5ITVJ?
YH-13 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTiSZlMUUN3ME2yNU45QCCwTR?= NGTVXoFUSU6JRWK=
HT-1080 NYHocHlvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnf0TWM2OD1{MT65N{BvVQ>? MVjTRW5ITVJ?
NCI-SNU-1 NVLUWJlsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIDpTndKSzVyPUKxMlk2KG6P NGS3OFBUSU6JRWK=
G-402 NVvr[3N1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVHJR|UxRTJ{LkG2JI5O Mmj6V2FPT0WU
786-0 Mn\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITDeYFKSzVyPUKyMlI6KG6P NH[0T4VUSU6JRWK=
ME-180 MkHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUWxPXBuUUN3ME2yNk41OyCwTR?= M{XBUHNCVkeHUh?=
NB69 NFPtfIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkSzTWM2OD1{Mj61N{BvVQ>? NY\0fnJDW0GQR1XS
J-RT3-T3-5 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTJ{Lkm2JI5O M1LUcHNCVkeHUh?=
TGBC1TKB MoruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLLTWM2OD1{Mz6wOUBvVQ>? NGXydIVUSU6JRWK=
SW780 NYTGVopvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4DvO2lEPTB;MkOuNVMhdk1? M123SHNCVkeHUh?=
MG-63 M{i2PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrsSYNbUUN3ME2yN{41PSCwTR?= M{e1dnNCVkeHUh?=
BV-173 NUi3UI85T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrETWM2OD1{Mz64O{BvVQ>? M3;UWHNCVkeHUh?=
CAL-51 NGTmNI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTJ|Lki5JI5O NIjhZ4pUSU6JRWK=
A375 M4nhTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV7VUpRNUUN3ME2yN{46OyCwTR?= NVXuXmFtW0GQR1XS
MEL-HO MnXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnQTWM2OD1{ND6wOEBvVQ>? NX7ufW9GW0GQR1XS
EFO-27 M{TGdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH32T|lKSzVyPUK0MlM{KG6P M2DG[nNCVkeHUh?=
Hs-578-T NFXLcHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIW2bWNKSzVyPUK0MlU5KG6P M4ruTXNCVkeHUh?=
NBsusSR MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml76TWM2OD1{ND62JI5O NGHTeYtUSU6JRWK=
CTB-1 NIHvNGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO2[lhKSzVyPUK0MlY4KG6P M17pbnNCVkeHUh?=
FTC-133 NUK5TZk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYPUNnNEUUN3ME2yOU4yKG6P NVnOc4tHW0GQR1XS
MOLT-4 NXTGTplFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4j3XmlEPTB;MkWuNVIhdk1? MUnTRW5ITVJ?
HO-1-N-1 MmfDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HmZWlEPTB;MkWuNVUhdk1? M4fmOHNCVkeHUh?=
ES3 NWXReFB4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVS5UYVMUUN3ME2yOU4zOiCwTR?= Mo\MV2FPT0WU
TI-73 NEOycoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\W[XFLUUN3ME2yOU4zQCCwTR?= MYTTRW5ITVJ?
MPP-89 NIm5eVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHWTWM2OD1{NT6zNkBvVQ>? M2HZdXNCVkeHUh?=
KYSE-150 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;1RXFFUUN3ME2yOU45QSCwTR?= NGCxNGdUSU6JRWK=
LXF-289 NEe1TJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml6zTWM2OD1{Nj6wOEBvVQ>? MVnTRW5ITVJ?
SK-LU-1 Ml75S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPGWlRuUUN3ME2yOk4yPyCwTR?= MnqyV2FPT0WU
HOP-92 M1rHXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzzS2pKSzVyPUK2MlQ5KG6P NFPyO4NUSU6JRWK=
HuO9 M2rpPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTJ4Lke2JI5O Mn7HV2FPT0WU
SW962 M3;3XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLTTWM2OD1{Nj63OkBvVQ>? MortV2FPT0WU
RS4-11 NFLGOmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXDWZVKSzVyPUK2MlkyKG6P MkfCV2FPT0WU
NCI-H292 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULucJBDUUN3ME2yO{BvVQ>? M1zWNnNCVkeHUh?=
DB NXeybZhoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTJ5LkO2JI5O MWDTRW5ITVJ?
SW1088 Mm\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M121R2lEPTB;MkiuNlkhdk1? NH7GclZUSU6JRWK=
A204 NHnnT2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTpfWo1UUN3ME2yPE41PyCwTR?= M{mwPXNCVkeHUh?=
A3-KAW NEXUdYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTJ6Lk[0JI5O MlLYV2FPT0WU
MV-4-11 NXm1cW96T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXPTWM2OD1{OD63JI5O NV[yNIdEW0GQR1XS
ES1 MmnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTJ6Lki0JI5O MoHsV2FPT0WU
ONS-76 NYHGS|BCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnUbm1lUUN3ME2yPU4xPSCwTR?= NUHGPYJuW0GQR1XS
D-263MG MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVO2b3dwUUN3ME2yPU4{PSCwTR?= NXXZWXRNW0GQR1XS
U-2-OS NGLMWWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrZVWhvUUN3ME2yPU42KG6P M2Ha[HNCVkeHUh?=
T98G NFLEcFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXmTWM2OD1{OT64PEBvVQ>? MWrTRW5ITVJ?
GI-ME-N NX33coZ7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn70TWM2OD1{OT65NUBvVQ>? MUHTRW5ITVJ?
BHT-101 M1XiXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\4SmxHUUN3ME2zNE4xPSCwTR?= NGTPZ|BUSU6JRWK=
NOS-1 MnXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3Xve2lEPTB;M{CuNVIhdk1? NHrRVI9USU6JRWK=
AsPC-1 M3;qNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTNyLkKgcm0> M1fOPXNCVkeHUh?=
QIMR-WIL Mn[5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2CyWmlEPTB;M{CuOkBvVQ>? NGLQXYRUSU6JRWK=
JVM-3 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYOzN|k{UUN3ME2zNE45OyCwTR?= M2HhdXNCVkeHUh?=
KU-19-19 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmOxTWM2OD1|MT6xN{BvVQ>? MVrTRW5ITVJ?
OVCAR-8 MnPnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1KxRWlEPTB;M{GuNlYhdk1? NV;GfXBxW0GQR1XS
BEN M135U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH;vT4tKSzVyPUOxMlY{KG6P NYW3W2lVW0GQR1XS
BE-13 MmDaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYD4dpR4UUN3ME2zNU45OiCwTR?= M2PZSnNCVkeHUh?=
EW-18 MlzFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTyTWM2OD1|MT64OkBvVQ>? NVrVNYF1W0GQR1XS
ECC10 M2TqN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLJR|UxRTNzLkm1JI5O NVWzd4duW0GQR1XS
CTV-1 Mn7GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX;JR|UxRTN{LkiyJI5O M2fGPHNCVkeHUh?=
COLO-800 MkjoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrmTWM2OD1|Mj65NkBvVQ>? MoXoV2FPT0WU
A2058 NWX1cotET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoLjTWM2OD1|Mz6yOUBvVQ>? NYLvTndPW0GQR1XS
VM-CUB-1 MmXWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH[0dJZKSzVyPUOzMlQ{KG6P M4LDcnNCVkeHUh?=
Ca9-22 NHniVm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MluwTWM2OD1|Mz61OUBvVQ>? NETnc5BUSU6JRWK=
COLO-684 MkfUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\CWZVKSzVyPUOzMlU5KG6P MWLTRW5ITVJ?
RPMI-8226 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTRV4FKSzVyPUOzMlgzKG6P NV;ZVWtUW0GQR1XS
SK-NEP-1 Mn;YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3q4VGlEPTB;M{SuNVUhdk1? NWK4c3JKW0GQR1XS
Becker NHHVcIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\CTWM2OD1|ND6yNUBvVQ>? MXfTRW5ITVJ?
NCI-H28 M4nje2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfWfVB2UUN3ME2zOE41PCCwTR?= MWfTRW5ITVJ?
CAL-120 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TYbGlEPTB;M{SuO|Ihdk1? Ml24V2FPT0WU
MDA-MB-157 Ml[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFjKWZhKSzVyPUO1MlQyKG6P Mln4V2FPT0WU
OVCAR-5 MmTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7TdmdQUUN3ME2zOU41PyCwTR?= NYnlUXZyW0GQR1XS
LAMA-84 NFvnWnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{DoTGlEPTB;M{WuPFchdk1? M4nvNnNCVkeHUh?=
CAKI-1 MnH2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXTXUlZrUUN3ME2zOk41OyCwTR?= MYfTRW5ITVJ?
Daoy MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLRTWM2OD1|Nj63JI5O MmHlV2FPT0WU
CAL-62 NX3XcIt{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3fofmlEPTB;M{[uPFYhdk1? MoP3V2FPT0WU
8-MG-BA M2jQR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTN5LkK1JI5O MoGxV2FPT0WU
8505C M2nxcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUfKSWtEUUN3ME2zO{42OSCwTR?= M{TKOHNCVkeHUh?=
LNCaP-Clone-FGC M1jmfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoDjTWM2OD1|Nz61PUBvVQ>? MU\TRW5ITVJ?
CAL-39 NHe5VlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTN5Lkmgcm0> MVrTRW5ITVJ?
MN-60 M4XiXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLCRZZsUUN3ME2zO{46PiCwTR?= NFXrPJVUSU6JRWK=
RKO MoL0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF\xbGRKSzVyPUO4MlM{KG6P NUTjOoFCW0GQR1XS
U251 Ml\US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPadHk1UUN3ME2zPE41OyCwTR?= NILMWlJUSU6JRWK=
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Saos-2 NHu2XJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnK3TWM2OD1zN{muN|Uhdk1? MXnTRW5ITVJ?
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JVM-2 NWfoZYc3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPxbY8yUUN3ME2zMlA{OTh6IN88US=> MVXTRW5ITVJ?
SW1116 NV3vWJJyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;r[2s1UUN3ME2zMlA2PDFzIN88US=> NHPmdYVUSU6JRWK=
MDA-MB-453 NUjkS3FFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTNwMUC0N|kh|ryP M3nJOnNCVkeHUh?=
Calu-6 NH3lS2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2DKdWlEPTB;Mz6xPVk4KM7:TR?= MYrTRW5ITVJ?
SHP-77 NUjKVHZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH:1[VhKSzVyPUOuOVI5KM7:TR?= MWfTRW5ITVJ?
Capan-2 M{DGZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NISyS5JKSzVyPUSuN|I2QDFizszN NGXaW|hUSU6JRWK=
SW948 NE\DcVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{f2cGlEPTB;ND63OFc4QSEQvF2= M4e2TnNCVkeHUh?=
HDLM-2 NXfHVW9HT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIOyTHFKSzVyPUWuNFc4OjVizszN NX;DZoI1W0GQR1XS
LAN-6 NWXQb|hRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVG2UYhPUUN3ME22MlIyPDl3IN88US=> NIjxeGlUSU6JRWK=
LU-135 M2HmVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFTDOmZKSzVyPU[uOFMxPzdizszN NGD3S5FUSU6JRWK=
T84 MlfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWn5[|U{UUN3ME22Mlk5PjRizszN M3rxVHNCVkeHUh?=
CAPAN-1 Mnf0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M370S2lEPTB;Nz62NlI{OyEQvF2= MmjHV2FPT0WU
SW1417 NXHCWIQyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHvxW2ZKSzVyPUeuPVE4OzFizszN MVjTRW5ITVJ?
BALL-1 M{HPb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRThwNUC0NFkh|ryP M17vfXNCVkeHUh?=
HT-29 M3i0eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIT0dY9KSzVyPUmuNFc2QTlizszN NYr1bFBYW0GQR1XS
C3A NWj5U3ZVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnuTWM2OD17Lki4N|k1KM7:TR?= MULTRW5ITVJ?
NCI-H1993 NXz4O4V5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYL3cVBLUUN3ME2xNE42ODhzIN88US=> NUTUTlNuW0GQR1XS
SK-MEL-1 NHjnWnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml61TWM2OD1zMT62Nlg6KM7:TR?= MV7TRW5ITVJ?
DU-145 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3XTWM2OD1zND61NFUzKM7:TR?= M3rmV3NCVkeHUh?=
KP-N-YN M1LUc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrC[nFGUUN3ME2xOE42OTB|IN88US=> M{TxdnNCVkeHUh?=
CCRF-CEM MlruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnXNIdXUUN3ME2xOE44QDB7IN88US=> NGDDdVJUSU6JRWK=
ZR-75-30 NF\3bmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEjZSGFKSzVyPUG2MlM{ODNizszN NHvyeFNUSU6JRWK=
A673 MmTjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3LS49KSzVyPUKwMlU2ODdizszN M1n5OHNCVkeHUh?=
K-562 M4TTNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M320PWlEPTB;MkiuOFE5OyEQvF2= MmD0V2FPT0WU

... 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 <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

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

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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).

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

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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID