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

10 Customer Reviews

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

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

     

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

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

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

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

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

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

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

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

     

     

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

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

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

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

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

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

     

     

     

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

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

     

     

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

     

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

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

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

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

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei NHjkU|hCdnSrbXnjdo9jcWGuIFHzd4F6 MV6xPEBp MoLDSG1UVw>? MkfHRY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? NHTFSnEzPDhyNUm0Oi=>
MCF7 MnjwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkX5NE4xOS1zMECg{txO NUPWWldWPDhiaB?= NIPndWdFVVOR NHvuXnpKSzVyPUCuO|Mh|ryP M1Sx[lI{QDdzOUC0
HCT116 MmPPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\iNE4xOS1zMECg{txO NELGNnE1QCCq M3z5b2ROW09? MXzJR|UxRTFwMU[g{txO M1roc|I{QDdzOUC0
U87MG M37WNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUmwMlAyNTFyMDFOwG0> MkjFOFghcA>? NIr0T3hFVVOR NFjEfnZKSzVyPUGuN|Ih|ryP MmTmNlM5PzF7MES=
HBC4 M3H4[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn65NE4xOS1zMECg{txO M4LpS|Q5KGh? MlfGUI9oKEeLNUC9MVgvPjFiTR?= NFzjcXMzOjN|NkK0Oi=>
BSY1 NHTpTIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3W1TVAvODFvMUCwJO69VQ>? MknkOFghcA>? NEjL[|FNd2diR1m1NF0uQC52ODDN M17me|IzOzN4MkS2
HBC5 M4L1Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDhNE4xOS1zMECg{txO M33RRlQ5KGh? M2HuZmxw\yCJSUWwQU04Njh5IF2= M3vmPFIzOzN4MkS2
MCF7 NVjOfpY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonQNE4xOS1zMECg{txO M37QRVQ5KGh? MnPkUI9oKEeLNUC9MVgvOTZiTR?= MkXVNlI{OzZ{NE[=
MDA-MB-231 NF;EelVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrNNpV1OC5yMT2xNFAh|ryP NU\t[odIPDhiaB?= NVrYUmxPVG:pIFfJOVA:NThwMEmgUS=> MoLINlI{OzZ{NE[=
U251 M3;lc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\pfGoxNjBzLUGwNEDPxE1? M17LO|Q5KGh? Mk\FUI9oKEeLNUC9MVcvPjZiTR?= NUDEc5JrOjJ|M{[yOFY>
SF268 M{DwVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M371UVAvODFvMUCwJO69VQ>? MYW0PEBp NXflTW5[VG:pIFfJOVA:NTdwOUKgUS=> M{PXeVIzOzN4MkS2
SF295 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYKwMlAyNTFyMDFOwG0> M2q5UFQ5KGh? M1rINWxw\yCJSUWwQU05NjNzIF2= MoPsNlI{OzZ{NE[=
SF539 Mn;MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGOzXYwxNjBzLUGwNEDPxE1? MWW0PEBp MYDMc4chT0l3ME2tPE42QSCP MmjKNlI{OzZ{NE[=
SNB75 NHqxNZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUCwMlAyNTFyMDFOwG0> MXG0PEBp MnXDUI9oKEeLNUC9MVgvPThiTR?= NHqwZ3ozOjN|NkK0Oi=>
SNB78 M4\CWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4n3fVAvODFvMUCwJO69VQ>? NGfsZ5M1QCCq M4Hzdmxw\yCJSUWwQU05NjZ3IF2= NYrLd2hXOjJ|M{[yOFY>
HCC2998 NWixU2p{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFzyS|QxNjBzLUGwNEDPxE1? MX60PEBp NH:yb|hNd2diR1m1NF0uQC5yNTDN NWq2clRuOjJ|M{[yOFY>
KM12 MmnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\zZ3p5OC5yMT2xNFAh|ryP M1Xk[|Q5KGh? NGfBVm1Nd2diR1m1NF0uPy53NDDN NETPdIIzOjN|NkK0Oi=>
HT-29 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzK[mUxNjBzLUGwNEDPxE1? MmCwOFghcA>? MX7Mc4chT0l3ME2tO{44PSCP M4LRW|IzOzN4MkS2
HCT15 M3nk[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWiwMlAyNTFyMDFOwG0> MmHKOFghcA>? M{TpXGxw\yCJSUWwQU05NjB|IF2= MoHENlI{OzZ{NE[=
HCT116 NFnodJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmHVNE4xOS1zMECg{txO NHnBT2o1QCCq MUDMc4chT0l3ME2tO{43OSCP M{Xw[lIzOzN4MkS2
NCI-H23 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzLT44xNjBzLUGwNEDPxE1? MUW0PEBp MmDmUI9oKEeLNUC9MVcvPjRiTR?= NYf1enFPOjJ|M{[yOFY>
NCI-H226 NWPuZlhLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkT4NE4xOS1zMECg{txO NEG1d2c1QCCq M2rmOWxw\yCJSUWwQU05NjR2IF2= NVPwRXRZOjJ|M{[yOFY>
NCI-H522 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUiwMlAyNTFyMDFOwG0> M1vCNFQ5KGh? M3zXZ2xw\yCJSUWwQU05NjR3IF2= NHi1Z4czOjN|NkK0Oi=>
NCI-H438 M2nBTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3nHdlAvODFvMUCwJO69VQ>? M3LmSFQ5KGh? M3:0VGxw\yCJSUWwQU05NjFzIF2= NVTBR4VFOjJ|M{[yOFY>
A549 NH\m[5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3ENJoxNjBzLUGwNEDPxE1? MUS0PEBp M3\ifWxw\yCJSUWwQU05NjB5IF2= MlXPNlI{OzZ{NE[=
DMS273 MmXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTac3VsOC5yMT2xNFAh|ryP NFTDPYQ1QCCq M{f5U2xw\yCJSUWwQU04NjhyIF2= M1jTR|IzOzN4MkS2
DMS114 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPJNE4xOS1zMECg{txO NYjnNpJxPDhiaB?= M2O5dmxw\yCJSUWwQU05NjN7IF2= NVXpTpU4OjJ|M{[yOFY>
LOXIMVI NGfMV4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fnOFAvODFvMUCwJO69VQ>? NUDZT2JZPDhiaB?= MkPEUI9oKEeLNUC9MVgvPjZiTR?= NFXOTWYzOjN|NkK0Oi=>
OVCAR3 NUXkR5ZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnaXYdVOC5yMT2xNFAh|ryP NG[3cIw1QCCq M2Xtfmxw\yCJSUWwQU05NjF5IF2= MUiyNlM{PjJ2Nh?=
OVCAR4 Mk\uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVWwMlAyNTFyMDFOwG0> NEXTPXY1QCCq M3;kTGxw\yCJSUWwQU05NjV6IF2= NHfLe|QzOjN|NkK0Oi=>
OVCAR5 MkjmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX:wMlAyNTFyMDFOwG0> M2rCT|Q5KGh? M1[y[2xw\yCJSUWwQU04NjV5IF2= M4DPTlIzOzN4MkS2
OVCAR8 NYXMVZlpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7EfocxNjBzLUGwNEDPxE1? M{OwR|Q5KGh? MUDMc4chT0l3ME2tO{45PCCP NWjpO5I3OjJ|M{[yOFY>
SKOV3 M1HOWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTYNE4xOS1zMECg{txO NX3HN4xjPDhiaB?= MXTMc4chT0l3ME2tPE41OSCP MnX4NlI{OzZ{NE[=
RXF631L MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7UNE4xOS1zMECg{txO NIXWV4I1QCCq NGLl[WdNd2diR1m1NF0uQC5{MTDN MnWzNlI{OzZ{NE[=
ACHN NGPpVWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYTnS5lCOC5yMT2xNFAh|ryP M1zrT|Q5KGh? M4jCT2xw\yCJSUWwQU04Njl3IF2= MUmyNlM{PjJ2Nh?=
St-4 M{K3TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M374PFAvODFvMUCwJO69VQ>? M2XQZ|Q5KGh? MUDMc4chT0l3ME2tO{41PyCP NEK2dW4zOjN|NkK0Oi=>
MKN1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;udpZuOC5yMT2xNFAh|ryP MVm0PEBp MX;Mc4chT0l3ME2tPE41OSCP NXLvSocxOjJ|M{[yOFY>
MKN7 Ml65S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWH2UXdiOC5yMT2xNFAh|ryP NYDsWmJ[PDhiaB?= MXPMc4chT0l3ME2tO{43QCCP M2XIUFIzOzN4MkS2
MKN28 NGn0[FhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzlW|ExNjBzLUGwNEDPxE1? MVO0PEBp NHfOXmVNd2diR1m1NF0uPy5yNzDN M{LvRlIzOzN4MkS2
MKN45 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfrdmNXOC5yMT2xNFAh|ryP MXW0PEBp MUnMc4chT0l3ME2tPE4{PCCP NID0[FQzOjN|NkK0Oi=>
MKN74 M3XJR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWn2WIlbOC5yMT2xNFAh|ryP M1fBcVQ5KGh? MmHwUI9oKEeLNUC9MVcvPDJiTR?= MXWyNlM{PjJ2Nh?=
DU145 NHz1emtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFL5OVIxNjBzLUGwNEDPxE1? NFHDWZA1QCCq NEf2cWVNd2diR1m1NF0uQC5zNjDN MYmyNlM{PjJ2Nh?=
PC3 NGHQeIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWTvVIVxOC5yMT2xNFAh|ryP NX7qcJpCPDhiaB?= MXHMc4chT0l3ME2tPE43PiCP MmHLNlI{OzZ{NE[=
Trypanosoma brucei brucei NHrBW2pHfW6ldHnvckBCe3OjeR?= MVKyNFAhdk1? NGnLOXMyOiCq NXXSUJd1TE2VTx?= NHXHSYxF\WO{ZXHz[UBqdiCyaH;zdIhwfGmmeXygbY5we2m2b3ygdIhwe3CqYYTlJIxmfmWu NIPnR4kzPDhyNUm0Oi=>
Trypanosoma brucei brucei NHLFeHBHfW6ldHnvckBCe3OjeR?= MU[xPEBp NFXpZ|ZFVVOR NF;6d4NKdmirYnn0bY9vKG:oIILlZ4VxfG:{LX3l[IlifGWmIHXu[I9kgXSxc3nzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIITyZY5{\mW{cnnuJJVxfGGtZR?= MV6yOFgxPTl2Nh?=
Trypanosoma brucei brucei MWnGeY5kfGmxbjDBd5NigQ>? NWq3dZlxOjByIH7N NHjK[IUyOiCq MkjpSG1UVw>? NFn4T3JG\m[nY4Sgc44he3CqaX7nc416dGWrbjDs[ZZmdA>? NF76WpczPDhyNUm0Oi=>
Trypanosoma brucei brucei MYnGeY5kfGmxbjDBd5NigQ>? M1\oOVIxOCCwTR?= M2DNVVEzKGh? M3i5OmROW09? MWTF[oZm[3Rib36gdIhwe3CqYYTp[Jlt[2ixbHnu[UBt\X[nbB?= MnHFNlQ5ODV7NE[=
UM-UC-3 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTNzNTDwUS=> NWP0b29MW0GQR1XS
SBC-1 Mn22S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTd2MjDwUS=> MnzoV2FPT0WU
MKN1 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTJwODDuUS=> MVTTRW5ITVJ?
NCI-H720 MnzDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\sNo1pUUN3ME2zMlU4KG6P MkfWV2FPT0WU
BFTC-909 NWrzUWtPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV7JR|UxRTNwN{Ggcm0> NF;x[mxUSU6JRWK=
BPH-1 MkXUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTRwN{[gcm0> MnnqV2FPT0WU
PC-3 MnThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTqTWM2OD13LkC5JI5O MWXTRW5ITVJ?
AN3-CA M2DC[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3v0UWlEPTB;NT61OkBvVQ>? NHiwe2ZUSU6JRWK=
HN NYPSfIVxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3ruOmlEPTB;NT65OkBvVQ>? MnjKV2FPT0WU
HCC2218 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfv[oxKSzVyPU[uOlEhdk1? NEDBRmJUSU6JRWK=
KP-4 NWnCXIxJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnpb5E5UUN3ME23JI5O Mn;VV2FPT0WU
LU-139 NGO4[GVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILtWHpKSzVyPUeuO|chdk1? NVu3SHBmW0GQR1XS
ETK-1 NWK5Tpc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTdwOEigcm0> MV;TRW5ITVJ?
Ramos-2G6-4C10 M2XEfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml65TWM2OD16LkS5JI5O MorIV2FPT0WU
MHH-PREB-1 Mn7nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7kcI1XUUN3ME25MlEzKG6P NVLsVIJ4W0GQR1XS
DU-4475 NXLrUI1KT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3Tqc2lEPTB;OT60OEBvVQ>? NFSxVmxUSU6JRWK=
NCI-H1666 NIjWbppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjlWIlSUUN3ME25MlcyKG6P MXPTRW5ITVJ?
CAMA-1 Mk\6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkT1TWM2OD17Lkigcm0> Mli4V2FPT0WU
TYK-nu MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYrJR|UxRTlwOUSgcm0> M37hNnNCVkeHUh?=
MFE-280 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{n1PWlEPTB;OT65PUBvVQ>? M1rpVnNCVkeHUh?=
A549 NYruWZVmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTFyLkG0JI5O MW\TRW5ITVJ?
769-P NF\FUoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfzSXVvUUN3ME2xNE41PCCwTR?= NWTrPJYxW0GQR1XS
L-363 NVjISI0zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXhTWM2OD1zMD62PUBvVQ>? Mm[yV2FPT0WU
ES8 MlrVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXsUHRKSzVyPUGwMlkhdk1? MXTTRW5ITVJ?
PA-1 M2PSUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHEPFNyUUN3ME2xNU45OiCwTR?= NGKxOGdUSU6JRWK=
Mewo M3rLbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13ISmlEPTB;MUGuPVkhdk1? MVfTRW5ITVJ?
HSC-3 NHvEO4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELH[INKSzVyPUGyMlIyKG6P M4r3eXNCVkeHUh?=
H4 NGnZZWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVz2XmNCUUN3ME2xNk43PyCwTR?= NHPCO5RUSU6JRWK=
BB65-RCC M{jnO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTF{LkeyJI5O MU\TRW5ITVJ?
NCI-H1793 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTF{LkiyJI5O NGTKdm1USU6JRWK=
KARPAS-45 Mo\4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;NV2lEPTB;MUOuOVEhdk1? MYjTRW5ITVJ?
GCT M3v1Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTaTWM2OD1zMz62PEBvVQ>? MXLTRW5ITVJ?
EoL-1 M33PU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1T1OGlEPTB;MUOuPVMhdk1? NEi2S|lUSU6JRWK=
LB2241-RCC MnPRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTF2LkCxJI5O NFWzU5dUSU6JRWK=
ES5 Ml25S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vZSGlEPTB;MUSuO|Qhdk1? M2XCVXNCVkeHUh?=
LOXIMVI NXXYSnIxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLsVIZ2UUN3ME2xOE46QSCwTR?= Mli3V2FPT0WU
COR-L105 NG\mcoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWjJR|UxRTF3LkC0JI5O NVzzOGlLW0GQR1XS
P12-ICHIKAWA M3\O[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTF3LkGgcm0> MXnTRW5ITVJ?
CHL-1 Ml3tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn;LTWM2OD1zNT60OUBvVQ>? NEfZT|ZUSU6JRWK=
VMRC-RCZ NV;oXnVVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWC1eZZwUUN3ME2xOU43OyCwTR?= MUHTRW5ITVJ?
HH M{\jSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUnJR|UxRTF3Lkegcm0> MUDTRW5ITVJ?
NUGC-3 MkjhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTpN2NMUUN3ME2xOk4{PCCwTR?= NYHBVGpzW0GQR1XS
EGI-1 NX7x[XFNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XU[WlEPTB;MU[uOFMhdk1? NYnucIZqW0GQR1XS
OS-RC-2 NHz3[I5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTF4LkS3JI5O NX\lOWg4W0GQR1XS
MOLT-16 MlTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzQZXROUUN3ME2xO{4yPSCwTR?= M1LEXHNCVkeHUh?=
NCI-H209 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX65fo1OUUN3ME2xO{4zQSCwTR?= MYHTRW5ITVJ?
697 NXL6[ZY{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3Tud2lEPTB;MUeuOFMhdk1? M13oRXNCVkeHUh?=
D-56MG NXHmcFg2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXvJR|UxRTF5Lk[5JI5O M3P4ZXNCVkeHUh?=
VA-ES-BJ MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnN[GNTUUN3ME2xO{45OyCwTR?= MkHNV2FPT0WU
EW-16 NHzWcHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTF6LkC0JI5O MYrTRW5ITVJ?
HGC-27 NVnybWJHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFG0[o5KSzVyPUG4MlA3KG6P NU\uZ4hWW0GQR1XS
ES7 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfNTWM2OD1zOD6wPUBvVQ>? NV\mOG5WW0GQR1XS
HuH-7 MnzOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mle2TWM2OD1zOD60JI5O MkLwV2FPT0WU
BCPAP NVrLRVdXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkLXTWM2OD1zOD62OUBvVQ>? MXrTRW5ITVJ?
SW1710 NIHmS5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTF6LkeyJI5O MXHTRW5ITVJ?
IST-MEL1 NHPId3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1TlOGlEPTB;MUiuO|chdk1? NVTydGVZW0GQR1XS
SF295 M4DrVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzVTWM2OD1zOD65N{BvVQ>? NXzVdW84W0GQR1XS
RPMI-7951 NWTiT2doT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnweotKSzVyPUG5MlI5KG6P MnzmV2FPT0WU
SF126 NWj5doMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorVTWM2OD1zOT60NUBvVQ>? NVvuXIpKW0GQR1XS
GAMG NIPoZYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWjJR|UxRTF7LkS4JI5O NVLrRopuW0GQR1XS
KNS-81-FD NXfQdJl3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\0emlEPTB;MUmuOVQhdk1? NE\0fpVUSU6JRWK=
RT-112 MlL6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLkd4piUUN3ME2xPU43PiCwTR?= MlfCV2FPT0WU
DEL M{\IeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;5c|lvUUN3ME2yNE41QSCwTR?= MlHhV2FPT0WU
CGTH-W-1 NYDiWlExT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\lem1mUUN3ME2yNE43OyCwTR?= Mn3QV2FPT0WU
HOS NVfaXmc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Moi2TWM2OD1{MT6wOkBvVQ>? MWPTRW5ITVJ?
ES4 Mn7JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfvTWM2OD1{MT6wPEBvVQ>? MWDTRW5ITVJ?
RXF393 M2G1[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTiVIsxUUN3ME2yNU41PSCwTR?= NH\yZ5pUSU6JRWK=
NCI-H2030 MlvNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37DUGlEPTB;MkGuOVIhdk1? MXnTRW5ITVJ?
YH-13 NY\NWllqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rFS2lEPTB;MkGuPFghdk1? NWfjcXRxW0GQR1XS
HT-1080 NUO2foQ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVr4c|JIUUN3ME2yNU46OyCwTR?= MYfTRW5ITVJ?
NCI-SNU-1 MlrvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYTPc3hvUUN3ME2yNU46PSCwTR?= MoTHV2FPT0WU
G-402 NX3PSFZKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEftV4JKSzVyPUKyMlE3KG6P M37ibXNCVkeHUh?=
786-0 M2K3W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzPTWM2OD1{Mj6yPUBvVQ>? MWLTRW5ITVJ?
ME-180 NHzKeppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\BOI1lUUN3ME2yNk41OyCwTR?= M3jsZ3NCVkeHUh?=
NB69 NXnlWI81T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnjkTWM2OD1{Mj61N{BvVQ>? NX7OPIdKW0GQR1XS
J-RT3-T3-5 NFvQZo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTJ{Lkm2JI5O M{fxe3NCVkeHUh?=
TGBC1TKB MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEDDeXBKSzVyPUKzMlA2KG6P M2m3cHNCVkeHUh?=
SW780 MoLGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTJ|LkGzJI5O NVLyVFdJW0GQR1XS
MG-63 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTJ|LkS1JI5O MVTTRW5ITVJ?
BV-173 NIPKRYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTJ|Lki3JI5O MmLIV2FPT0WU
CAL-51 NUOwPHR3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\sSGlEPTB;MkOuPFkhdk1? MWTTRW5ITVJ?
A375 NWKz[JF3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlzKTWM2OD1{Mz65N{BvVQ>? MkjEV2FPT0WU
MEL-HO M2HkZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFPmXo5KSzVyPUK0MlA1KG6P NILuPIVUSU6JRWK=
EFO-27 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTJ2LkOzJI5O NF22OZpUSU6JRWK=
Hs-578-T MljDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWfJR|UxRTJ2LkW4JI5O NYTFfmU5W0GQR1XS
NBsusSR NE\hb4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTJ2Lk[gcm0> NI\yO4RUSU6JRWK=
CTB-1 MnHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2PGXmlEPTB;MkSuOlchdk1? NI[1RnFUSU6JRWK=
FTC-133 M{S3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRTJ3LkGgcm0> Mn;0V2FPT0WU
MOLT-4 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;DbmlEPTB;MkWuNVIhdk1? MkjjV2FPT0WU
HO-1-N-1 MnP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXJTWM2OD1{NT6xOUBvVQ>? NWfJfWZxW0GQR1XS
ES3 NYf4Wo1kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M173SmlEPTB;MkWuNlIhdk1? NG\1RnZUSU6JRWK=
TI-73 M2Kw[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLQTWM2OD1{NT6yPEBvVQ>? NH[zeoFUSU6JRWK=
MPP-89 NXy5ZnJnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV3JR|UxRTJ3LkOyJI5O NITCWoRUSU6JRWK=
KYSE-150 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTJ3Lki5JI5O NIDwRmJUSU6JRWK=
LXF-289 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHRSGJbUUN3ME2yOk4xPCCwTR?= NXqzWW9yW0GQR1XS
SK-LU-1 MkDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rH[WlEPTB;Mk[uNVchdk1? MmjNV2FPT0WU
HOP-92 NHXZeJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjycnpKSzVyPUK2MlQ5KG6P MnPjV2FPT0WU
HuO9 M13jemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRTJ4Lke2JI5O NGTVW4JUSU6JRWK=
SW962 NFjqPXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjOUHhKSzVyPUK2Mlc3KG6P NXfaR3E{W0GQR1XS
RS4-11 NFn1dFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\NXHZ1UUN3ME2yOk46OSCwTR?= MX;TRW5ITVJ?
NCI-H292 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2S5R2lEPTB;Mkegcm0> MXTTRW5ITVJ?
DB MoKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTJc3pIUUN3ME2yO{4{PiCwTR?= MlLUV2FPT0WU
SW1088 MoexS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3OyTmlEPTB;MkiuNlkhdk1? Ml7CV2FPT0WU
A204 M1G2Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFrFeVZKSzVyPUK4MlQ4KG6P NIjo[GNUSU6JRWK=
A3-KAW M{XZXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHxTWM2OD1{OD62OEBvVQ>? M1jrcnNCVkeHUh?=
MV-4-11 M3PpXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPXdZRQUUN3ME2yPE44KG6P MmLlV2FPT0WU
ES1 NEjVPZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2XobGlEPTB;MkiuPFQhdk1? MnrwV2FPT0WU
ONS-76 NIfB[nJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nhUmlEPTB;MkmuNFUhdk1? M1fpbHNCVkeHUh?=
D-263MG MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\hTWM2OD1{OT6zOUBvVQ>? MXPTRW5ITVJ?
U-2-OS MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7MTWM2OD1{OT61JI5O M2nheXNCVkeHUh?=
T98G NWTMdHNbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHHTWM2OD1{OT64PEBvVQ>? MWrTRW5ITVJ?
GI-ME-N NFzhOYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmHTTWM2OD1{OT65NUBvVQ>? MkXVV2FPT0WU
BHT-101 MkPNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2DzZWlEPTB;M{CuNFUhdk1? M3\Fe3NCVkeHUh?=
NOS-1 NVrNVW95T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofzTWM2OD1|MD6xNkBvVQ>? NFPhOnNUSU6JRWK=
AsPC-1 NUXuWHAyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfxW4dKSzVyPUOwMlIhdk1? MYfTRW5ITVJ?
QIMR-WIL M4Djdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHYZ5lKSzVyPUOwMlYhdk1? NEj6OZRUSU6JRWK=
JVM-3 NVTST2d6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4Lv[GlEPTB;M{CuPFMhdk1? NGTwdlNUSU6JRWK=
KU-19-19 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTNzLkGzJI5O NIG1WlVUSU6JRWK=
OVCAR-8 NFzZSWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\6TldVUUN3ME2zNU4zPiCwTR?= MYXTRW5ITVJ?
BEN M1PlVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkK5TWM2OD1|MT62N{BvVQ>? MVzTRW5ITVJ?
BE-13 NEm5UmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoDyTWM2OD1|MT64NkBvVQ>? MoOzV2FPT0WU
EW-18 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LVVGlEPTB;M{GuPFYhdk1? MWjTRW5ITVJ?
ECC10 NVjIXIp[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\3bmlEPTB;M{GuPVUhdk1? NIW3b3JUSU6JRWK=
CTV-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13qd2lEPTB;M{KuPFIhdk1? NUP3NWxTW0GQR1XS
COLO-800 Ml\IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUP0bGNEUUN3ME2zNk46OiCwTR?= NVGxfXc4W0GQR1XS
A2058 MnXiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXuPIlKSzVyPUOzMlI2KG6P NFL6VY5USU6JRWK=
VM-CUB-1 NVKxUmxHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2jPV2lEPTB;M{OuOFMhdk1? M4DYbXNCVkeHUh?=
Ca9-22 M1rlWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3ubmtKSzVyPUOzMlU2KG6P M3rKNXNCVkeHUh?=
COLO-684 NELk[pdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWW2UIFbUUN3ME2zN{42QCCwTR?= MkjjV2FPT0WU
RPMI-8226 NG[xVXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PpPGlEPTB;M{OuPFIhdk1? M1;1bnNCVkeHUh?=
SK-NEP-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEj3SZBKSzVyPUO0MlE2KG6P NF7XV3JUSU6JRWK=
Becker MlXvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTN2LkKxJI5O NY\yWIZFW0GQR1XS
NCI-H28 NVO2b5d[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3GwSGlEPTB;M{SuOFQhdk1? Mm\nV2FPT0WU
CAL-120 NH;sNGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4rZNmlEPTB;M{SuO|Ihdk1? M1nU[XNCVkeHUh?=
MDA-MB-157 NI\0PXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzPSFdKSzVyPUO1MlQyKG6P NFrtVoxUSU6JRWK=
OVCAR-5 NUDOb45pT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1X4RWlEPTB;M{WuOFchdk1? NHH0fFRUSU6JRWK=
LAMA-84 M2DCfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zMZ2lEPTB;M{WuPFchdk1? Mmq2V2FPT0WU
CAKI-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XWPWlEPTB;M{[uOFMhdk1? NUDhTJNpW0GQR1XS
Daoy M3jUbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;sWWlEPTB;M{[uO{BvVQ>? MXfTRW5ITVJ?
CAL-62 NX\EdlUxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVqxdmxWUUN3ME2zOk45PiCwTR?= MXjTRW5ITVJ?
8-MG-BA MnjJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVS5NGZGUUN3ME2zO{4zPSCwTR?= Ml72V2FPT0WU
8505C M{DoS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjES2NtUUN3ME2zO{42OSCwTR?= MVrTRW5ITVJ?
LNCaP-Clone-FGC M3;E[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVO4VIFPUUN3ME2zO{42QSCwTR?= NIHZcpVUSU6JRWK=
CAL-39 M4XEXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTN5Lkmgcm0> NYLrRmV3W0GQR1XS
MN-60 MknxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTN5Lkm2JI5O MYDTRW5ITVJ?
RKO NHjOTZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3i5ZWlEPTB;M{iuN|Mhdk1? NFH5[3JUSU6JRWK=
U251 NFTjTI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrsU5lyUUN3ME2zPE41OyCwTR?= MnjjV2FPT0WU
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JVM-2 NEnXfo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrJTWM2OD1|LkCzNVg5KM7:TR?= MkLxV2FPT0WU
SW1116 NGLEPW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVLJR|UxRTNwMEW0NVEh|ryP Mn\2V2FPT0WU
MDA-MB-453 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjkTWM2OD1|LkGwOFM6KM7:TR?= NV71NVNJW0GQR1XS
Calu-6 NF7lN2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUH5cZNLUUN3ME2zMlE6QTdizszN MnfPV2FPT0WU
SHP-77 MnO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHIdZVOUUN3ME2zMlUzQCEQvF2= M1nNRnNCVkeHUh?=
Capan-2 Mnj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NED0NmhKSzVyPUSuN|I2QDFizszN NH;hZ3dUSU6JRWK=
SW948 M1XYZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzkTWM2OD12Lke0O|c6KM7:TR?= NHHwbVBUSU6JRWK=
HDLM-2 M3nDOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnzqTWM2OD13LkC3O|I2KM7:TR?= NYL0V5BkW0GQR1XS
LAN-6 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTZwMkG0PVUh|ryP MUTTRW5ITVJ?
LU-135 M333dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnHoTWM2OD14LkSzNFc4KM7:TR?= M4myVnNCVkeHUh?=
T84 M33OPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTZwOUi2OEDPxE1? MmS3V2FPT0WU
CAPAN-1 NEDuZopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTdwNkKyN|Mh|ryP MnjCV2FPT0WU
SW1417 MnPNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXP5OoxzUUN3ME23MlkyPzNzIN88US=> NUXpXo1kW0GQR1XS
BALL-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;FfWlEPTB;OD61NFQxQSEQvF2= MX;TRW5ITVJ?
HT-29 MnTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfQZWNoUUN3ME25MlA4PTl7IN88US=> NI\w[JJUSU6JRWK=
C3A M4jZXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\J[HdKSzVyPUmuPFg{QTRizszN NV3LcXRGW0GQR1XS
NCI-H1993 M{jCdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPpTWM2OD1zMD61NFgyKM7:TR?= MnP3V2FPT0WU
SK-MEL-1 MkfrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXQTWM2OD1zMT62Nlg6KM7:TR?= MlfSV2FPT0WU
DU-145 NX7HN|dIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrm[XJYUUN3ME2xOE42ODV{IN88US=> MlTGV2FPT0WU
KP-N-YN NGTQWmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXKVGx5UUN3ME2xOE42OTB|IN88US=> NWG1WpFOW0GQR1XS
CCRF-CEM MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jydWlEPTB;MUSuO|gxQSEQvF2= MlTZV2FPT0WU
ZR-75-30 NVHzcGt2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13xfWlEPTB;MU[uN|MxOyEQvF2= M4\tfHNCVkeHUh?=
A673 M4Xxc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn;yTWM2OD1{MD61OVA4KM7:TR?= NXHlVZVtW0GQR1XS
K-562 MorVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXjB[lA1UUN3ME2yPE41OTh|IN88US=> NGWwZ4ZUSU6JRWK=

... 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 slightly soluble or insoluble
In vivo Add solvents individually and in order:
NMP+polyethylene glycol 300 (10+90, v+v)
30 mg/mL

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

Chemical Information

Molecular Weight 469.55
Formula

C30H23N5O

CAS No. 915019-65-7
Storage powder
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).

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Dilution Calculator

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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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID