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 88 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 NETMXVVCdnSrbXnjdo9jcWGuIFHzd4F6 M2fj[FE5KGh? NWO4V3BNTE2VTx?= MYfBcpRqfHK7cHHuc5NwdWGuIHHjeIl3cXS7IIfpeIghTUN3MDDv[kAxNjByMkWg{txO MWGyOFgxPTl2Nh?=
MCF7 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3zURVAvODFvMUCwJO69VQ>? MWO0PEBp MVzEUXNQ NH7nPFhKSzVyPUCuO|Mh|ryP NULXWYNtOjN6N{G5NFQ>
HCT116 M33Ndmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTxNE4xOS1zMECg{txO M{TIUVQ5KGh? MmnzSG1UVw>? NIXxN4ZKSzVyPUGuNVYh|ryP MW[yN|g4OTlyNB?=
U87MG MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHHTldOOC5yMT2xNFAh|ryP NVjkS4toPDhiaB?= Mnz1SG1UVw>? MnLQTWM2OD1zLkOyJO69VQ>? NULwTG4zOjN6N{G5NFQ>
HBC4 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFryb|kxNjBzLUGwNEDPxE1? M3fvd|Q5KGh? MmPYUI9oKEeLNUC9MVgvPjFiTR?= MkHYNlI{OzZ{NE[=
BSY1 NGCyUGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYGwMlAyNTFyMDFOwG0> MlHsOFghcA>? NIjzT3BNd2diR1m1NF0uQC52ODDN NUTa[ZBJOjJ|M{[yOFY>
HBC5 NX2z[mhCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUWwMlAyNTFyMDFOwG0> NGnPO4U1QCCq M1\Ke2xw\yCJSUWwQU04Njh5IF2= MXKyNlM{PjJ2Nh?=
MCF7 NFr0O2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX:wMlAyNTFyMDFOwG0> M{XsRlQ5KGh? M3TQdmxw\yCJSUWwQU05NjF4IF2= NHrmd2IzOjN|NkK0Oi=>
MDA-MB-231 M2XrUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXuwMlAyNTFyMDFOwG0> MljnOFghcA>? MoHDUI9oKEeLNUC9MVgvODliTR?= MWSyNlM{PjJ2Nh?=
U251 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIHuOGUxNjBzLUGwNEDPxE1? MnXFOFghcA>? NFzTVJBNd2diR1m1NF0uPy54NjDN NYnJU|N6OjJ|M{[yOFY>
SF268 MmrHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XOSVAvODFvMUCwJO69VQ>? MYO0PEBp NFzGWoJNd2diR1m1NF0uPy57MjDN MUWyNlM{PjJ2Nh?=
SF295 NWfudYZPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{W0TlAvODFvMUCwJO69VQ>? MUO0PEBp M1HCdGxw\yCJSUWwQU05NjNzIF2= NVfndHRUOjJ|M{[yOFY>
SF539 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV3pPJpVOC5yMT2xNFAh|ryP MonsOFghcA>? NYLQWpllVG:pIFfJOVA:NThwNUmgUS=> Mm\sNlI{OzZ{NE[=
SNB75 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVOwMlAyNTFyMDFOwG0> MVq0PEBp MVrMc4chT0l3ME2tPE42QCCP M2HoV|IzOzN4MkS2
SNB78 NVHuU2N7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTYSWoxNjBzLUGwNEDPxE1? MYW0PEBp M4nxXGxw\yCJSUWwQU05NjZ3IF2= NH;hRoQzOjN|NkK0Oi=>
HCC2998 NGXObmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\vS3VZOC5yMT2xNFAh|ryP MlLqOFghcA>? NH:zVm9Nd2diR1m1NF0uQC5yNTDN NH7UcJozOjN|NkK0Oi=>
KM12 MnPHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnZTYMxNjBzLUGwNEDPxE1? NGH4ZmM1QCCq NWKxT5VJVG:pIFfJOVA:NTdwNUSgUS=> MnvGNlI{OzZ{NE[=
HT-29 MkD4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn7nNE4xOS1zMECg{txO M1SxOFQ5KGh? MX7Mc4chT0l3ME2tO{44PSCP M4\pXVIzOzN4MkS2
HCT15 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHscGQxNjBzLUGwNEDPxE1? MYS0PEBp NGfDbINNd2diR1m1NF0uQC5yMzDN NXyxPGhDOjJ|M{[yOFY>
HCT116 NWfJZmttT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVqwMlAyNTFyMDFOwG0> MYi0PEBp MYjMc4chT0l3ME2tO{43OSCP MmruNlI{OzZ{NE[=
NCI-H23 NIHtSIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NECzb4IxNjBzLUGwNEDPxE1? MXq0PEBp MleyUI9oKEeLNUC9MVcvPjRiTR?= NFjPNYEzOjN|NkK0Oi=>
NCI-H226 NUnPeZdZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXOwMlAyNTFyMDFOwG0> MVm0PEBp NYnJZ4ZHVG:pIFfJOVA:NThwNESgUS=> MmW5NlI{OzZ{NE[=
NCI-H522 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGHxSVExNjBzLUGwNEDPxE1? NUDKXVdUPDhiaB?= MojzUI9oKEeLNUC9MVgvPDViTR?= NXz3TY02OjJ|M{[yOFY>
NCI-H438 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUCwMlAyNTFyMDFOwG0> M3PBfFQ5KGh? MVvMc4chT0l3ME2tPE4yOSCP MmrsNlI{OzZ{NE[=
A549 M4DGNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYmwMlAyNTFyMDFOwG0> NXy3R2VHPDhiaB?= MoCzUI9oKEeLNUC9MVgvODdiTR?= NHjpTXAzOjN|NkK0Oi=>
DMS273 NHnN[FJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MViwMlAyNTFyMDFOwG0> Mn3OOFghcA>? NE\nWFhNd2diR1m1NF0uPy56MDDN MVSyNlM{PjJ2Nh?=
DMS114 NUfafGx6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfQNE4xOS1zMECg{txO MknaOFghcA>? NHniVXJNd2diR1m1NF0uQC5|OTDN NX;zdHVHOjJ|M{[yOFY>
LOXIMVI M2\mW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7udlIxNjBzLUGwNEDPxE1? NI\YfJE1QCCq M{LBWWxw\yCJSUWwQU05NjZ4IF2= NVPpeYN6OjJ|M{[yOFY>
OVCAR3 NFPWeHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEjrUZUxNjBzLUGwNEDPxE1? NF;ESYw1QCCq MWrMc4chT0l3ME2tPE4yPyCP NYrDbYtuOjJ|M{[yOFY>
OVCAR4 MorXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVL3V|BMOC5yMT2xNFAh|ryP MluyOFghcA>? M{TvNGxw\yCJSUWwQU05NjV6IF2= MWCyNlM{PjJ2Nh?=
OVCAR5 M2DCOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4jYTFAvODFvMUCwJO69VQ>? NUnBd5FDPDhiaB?= NGXvTW5Nd2diR1m1NF0uPy53NzDN NIXuT2wzOjN|NkK0Oi=>
OVCAR8 Mm\ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLHeFMxNjBzLUGwNEDPxE1? NHLsWZI1QCCq MV\Mc4chT0l3ME2tO{45PCCP MXiyNlM{PjJ2Nh?=
SKOV3 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVWwMlAyNTFyMDFOwG0> NWHXc|U2PDhiaB?= M13PWGxw\yCJSUWwQU05NjRzIF2= MVmyNlM{PjJ2Nh?=
RXF631L MlPnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moj4NE4xOS1zMECg{txO MVK0PEBp NHfMfoNNd2diR1m1NF0uQC5{MTDN NF\KPIQzOjN|NkK0Oi=>
ACHN NWj3OWdWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG[zW28xNjBzLUGwNEDPxE1? M{TnfFQ5KGh? Mn7TUI9oKEeLNUC9MVcvQTViTR?= Ml7nNlI{OzZ{NE[=
St-4 NES4eGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXkcJoxNjBzLUGwNEDPxE1? MoDXOFghcA>? MVPMc4chT0l3ME2tO{41PyCP NGLNfHUzOjN|NkK0Oi=>
MKN1 NHzWbWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2D5RVAvODFvMUCwJO69VQ>? MUm0PEBp NFvDRmJNd2diR1m1NF0uQC52MTDN NF3HV5EzOjN|NkK0Oi=>
MKN7 MofLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV[wMlAyNTFyMDFOwG0> M3PPZVQ5KGh? M{nCcmxw\yCJSUWwQU04NjZ6IF2= M2XqXlIzOzN4MkS2
MKN28 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEDablQxNjBzLUGwNEDPxE1? NWrPXmF3PDhiaB?= M2S3UGxw\yCJSUWwQU04NjB5IF2= MViyNlM{PjJ2Nh?=
MKN45 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXqbmUxNjBzLUGwNEDPxE1? M4\5blQ5KGh? NHHj[4VNd2diR1m1NF0uQC5|NDDN MknrNlI{OzZ{NE[=
MKN74 NW\oT3M1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWOwMlAyNTFyMDFOwG0> MmDsOFghcA>? M1js[mxw\yCJSUWwQU04NjR{IF2= NFPsbJczOjN|NkK0Oi=>
DU145 Mof5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{S3WVAvODFvMUCwJO69VQ>? NEHPOmU1QCCq NFOwZ5pNd2diR1m1NF0uQC5zNjDN M1;SVlIzOzN4MkS2
PC3 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\4NE4xOS1zMECg{txO M3K1cVQ5KGh? NH;GcZFNd2diR1m1NF0uQC54NjDN NIjUU5AzOjN|NkK0Oi=>
Trypanosoma brucei brucei Ml7FSpVv[3Srb36gRZN{[Xl? NInMd5MzODBibl2= NVrucFZkOTJiaB?= NITHXYFFVVOR MYjE[YNz\WG|ZTDpckBxcG:|cHjveIllgWxiaX7vd4l1d2xicHjvd5Bp[XSnIHzleoVt NHm1W5kzPDhyNUm0Oi=>
Trypanosoma brucei brucei MXrGeY5kfGmxbjDBd5NigQ>? M1LOTFE5KGh? NVn3d5JoTE2VTx?= MkS5TY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? NGD4RZozPDhyNUm0Oi=>
Trypanosoma brucei brucei M2T4cmZ2dmO2aX;uJGF{e2G7 MWOyNFAhdk1? M1jQ[|EzKGh? M1HNW2ROW09? MWfF[oZm[3Rib36gd5BpcW6pb335cIVqdiCuZY\lcC=> NFPyZWIzPDhyNUm0Oi=>
Trypanosoma brucei brucei MUHGeY5kfGmxbjDBd5NigQ>? M3v1XFIxOCCwTR?= M4PkXlEzKGh? NWC0XW9kTE2VTx?= NH\UU|dG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> MUGyOFgxPTl2Nh?=
UM-UC-3 M2mzPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4ThWmlEPTB;M{G1JJBO NXHRZ5BUW0GQR1XS
SBC-1 Mmn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{e5OWlEPTB;N{SyJJBO MW\TRW5ITVJ?
MKN1 MnjRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mke1TWM2OD1{Lkigcm0> NX\uUYhtW0GQR1XS
NCI-H720 MkXmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3z3[GlEPTB;Mz61O{BvVQ>? M1y3UnNCVkeHUh?=
BFTC-909 NIPifYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYD1PHo2UUN3ME2zMlcyKG6P M1fFWnNCVkeHUh?=
BPH-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HLVGlEPTB;ND63OkBvVQ>? MnfLV2FPT0WU
PC-3 Mk\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXhSYxKSzVyPUWuNFkhdk1? M2\wb3NCVkeHUh?=
AN3-CA M{DBTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGrwfWlKSzVyPUWuOVYhdk1? MUnTRW5ITVJ?
HN MoP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzL[2NKSzVyPUWuPVYhdk1? M13NXHNCVkeHUh?=
HCC2218 NGH1O5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonxTWM2OD14Lk[xJI5O MUXTRW5ITVJ?
KP-4 MmD1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDDcWNKSzVyPUegcm0> NFX4bZpUSU6JRWK=
LU-139 NWDSNXkyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTdwN{egcm0> MXjTRW5ITVJ?
ETK-1 Mn7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFu0RolKSzVyPUeuPFghdk1? MoDzV2FPT0WU
Ramos-2G6-4C10 MoPSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXVcIt4UUN3ME24MlQ6KG6P MUDTRW5ITVJ?
MHH-PREB-1 M{S0OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TaSWlEPTB;OT6xNkBvVQ>? M4XWcXNCVkeHUh?=
DU-4475 NUDpWFltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4TaSGlEPTB;OT60OEBvVQ>? NG\iR|NUSU6JRWK=
NCI-H1666 MlLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTlwN{Ggcm0> MmHRV2FPT0WU
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TYK-nu NUPQSnpzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XqcmlEPTB;OT65OEBvVQ>? NYfqTWFVW0GQR1XS
MFE-280 MnfsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzmTZA1UUN3ME25Mlk6KG6P MnGzV2FPT0WU
A549 MmTOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLJTWM2OD1zMD6xOEBvVQ>? MUXTRW5ITVJ?
769-P MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjtSlJ1UUN3ME2xNE41PCCwTR?= NYjvUHo1W0GQR1XS
L-363 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGX4cY5KSzVyPUGwMlY6KG6P MYHTRW5ITVJ?
ES8 NWnmO5luT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rldGlEPTB;MUCuPUBvVQ>? MXXTRW5ITVJ?
PA-1 M{TTSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zVW2lEPTB;MUGuPFIhdk1? NYPRc4Z3W0GQR1XS
Mewo NU\WZXdnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHUVll6UUN3ME2xNU46QSCwTR?= NYDwdpplW0GQR1XS
HSC-3 M3XQRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\SeFZKSzVyPUGyMlIyKG6P MWHTRW5ITVJ?
H4 NU\VVYJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nYZ2lEPTB;MUKuOlchdk1? NUDFcXJlW0GQR1XS
BB65-RCC M1\nU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fQWGlEPTB;MUKuO|Ihdk1? MkDSV2FPT0WU
NCI-H1793 NXHIOHlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnHTWM2OD1zMj64NkBvVQ>? NXTHT|Y3W0GQR1XS
KARPAS-45 M{Tsbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHENpFKSzVyPUGzMlUyKG6P MVnTRW5ITVJ?
GCT MoHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXHJR|UxRTF|Lk[4JI5O NGf1RmxUSU6JRWK=
EoL-1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHS5d21KSzVyPUGzMlk{KG6P MVLTRW5ITVJ?
LB2241-RCC M2fXTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjWN4pKSzVyPUG0MlAyKG6P M1;1WHNCVkeHUh?=
ES5 NG[yW|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjXUYJvUUN3ME2xOE44PCCwTR?= NYrwOoRIW0GQR1XS
LOXIMVI MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTxTWM2OD1zND65PUBvVQ>? MUXTRW5ITVJ?
COR-L105 M3fkcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{m4VWlEPTB;MUWuNFQhdk1? NIPXcXhUSU6JRWK=
P12-ICHIKAWA MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\rTWM2OD1zNT6xJI5O MoHRV2FPT0WU
CHL-1 NVv0W5Z2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXJe49wUUN3ME2xOU41PSCwTR?= MnLNV2FPT0WU
VMRC-RCZ M1\zPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPRN4tKSzVyPUG1MlY{KG6P M1nFbnNCVkeHUh?=
HH MoO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn:1TWM2OD1zNT63JI5O NF\4NplUSU6JRWK=
NUGC-3 NHv0cYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTF4LkO0JI5O NWjaR|hpW0GQR1XS
EGI-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTF4LkSzJI5O M1fhOnNCVkeHUh?=
OS-RC-2 NEDKTmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTF4LkS3JI5O MXjTRW5ITVJ?
MOLT-16 NUPGWoNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnnWZhKSzVyPUG3MlE2KG6P MlzvV2FPT0WU
NCI-H209 MlTsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljJTWM2OD1zNz6yPUBvVQ>? NF76N3lUSU6JRWK=
697 Mom5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\QWGlEPTB;MUeuOFMhdk1? MkK5V2FPT0WU
D-56MG NEXsOVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTF5Lk[5JI5O M4j1O3NCVkeHUh?=
VA-ES-BJ NVzGfXU4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTF5LkizJI5O M37HOHNCVkeHUh?=
EW-16 NH\OSJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HmPGlEPTB;MUiuNFQhdk1? NVe1N3R6W0GQR1XS
HGC-27 MkmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDhUFRKSzVyPUG4MlA3KG6P NVLBRlllW0GQR1XS
ES7 M3\4Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYPsd29TUUN3ME2xPE4xQSCwTR?= Mom5V2FPT0WU
HuH-7 M2H6R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTF6LkSgcm0> MmDMV2FPT0WU
BCPAP NWSwU3dkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3fKfGlEPTB;MUiuOlUhdk1? M3jNPXNCVkeHUh?=
SW1710 NYSyOZNoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13RdGlEPTB;MUiuO|Ihdk1? M3[3cnNCVkeHUh?=
IST-MEL1 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLzVXJRUUN3ME2xPE44PyCwTR?= MXfTRW5ITVJ?
SF295 NES3NYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXwTWM2OD1zOD65N{BvVQ>? NGj1T3lUSU6JRWK=
RPMI-7951 NUfzbY5DT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3QT2xKSzVyPUG5MlI5KG6P MleyV2FPT0WU
SF126 Ml\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjTdW9KSzVyPUG5MlQyKG6P NXS3Rnp2W0GQR1XS
GAMG MoGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TKdWlEPTB;MUmuOFghdk1? M2XqV3NCVkeHUh?=
KNS-81-FD NFO1UZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13qTmlEPTB;MUmuOVQhdk1? MnvmV2FPT0WU
RT-112 MmXrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPYUmdKSzVyPUG5MlY3KG6P Mm\HV2FPT0WU
DEL MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoC1TWM2OD1{MD60PUBvVQ>? NGrSdFRUSU6JRWK=
CGTH-W-1 M3fIcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MULJR|UxRTJyLk[zJI5O Mk\lV2FPT0WU
HOS NGnjdYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTJzLkC2JI5O MlfjV2FPT0WU
ES4 MlTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4O3TmlEPTB;MkGuNFghdk1? MkjjV2FPT0WU
RXF393 NWLFNowzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLxdGlKSzVyPUKxMlQ2KG6P NILsXVNUSU6JRWK=
NCI-H2030 Mk\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoKzTWM2OD1{MT61NkBvVQ>? MlXUV2FPT0WU
YH-13 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljCTWM2OD1{MT64PEBvVQ>? NE[0O|ZUSU6JRWK=
HT-1080 NIfYZ|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTJzLkmzJI5O Mm\2V2FPT0WU
NCI-SNU-1 NYXDNpJvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;MNpJEUUN3ME2yNU46PSCwTR?= M3zFT3NCVkeHUh?=
G-402 M2TCW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlW4TWM2OD1{Mj6xOkBvVQ>? NFG4fnlUSU6JRWK=
786-0 MoTUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXroUJo3UUN3ME2yNk4zQSCwTR?= M2DqRnNCVkeHUh?=
ME-180 NFTqd2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXkTWM2OD1{Mj60N{BvVQ>? MlS5V2FPT0WU
NB69 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfNfWpKSzVyPUKyMlU{KG6P M{DaNnNCVkeHUh?=
J-RT3-T3-5 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnniTWM2OD1{Mj65OkBvVQ>? NGPLeWpUSU6JRWK=
TGBC1TKB NVvhUVVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXQTWM2OD1{Mz6wOUBvVQ>? NGq0WlFUSU6JRWK=
SW780 MmD2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrxdFZKSzVyPUKzMlE{KG6P MW\TRW5ITVJ?
MG-63 MkfsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX63fVVQUUN3ME2yN{41PSCwTR?= M{H5UnNCVkeHUh?=
BV-173 M1zNOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLOTWM2OD1{Mz64O{BvVQ>? NVfVXXdWW0GQR1XS
CAL-51 NFiy[nlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn35TWM2OD1{Mz64PUBvVQ>? NF\KbmlUSU6JRWK=
A375 MnHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjoV4JKSzVyPUKzMlk{KG6P NWrqc|d1W0GQR1XS
MEL-HO M1Sz[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXSTWM2OD1{ND6wOEBvVQ>? Mn6zV2FPT0WU
EFO-27 NWX1Om5RT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4m1fmlEPTB;MkSuN|Mhdk1? NGXHcplUSU6JRWK=
Hs-578-T M4jk[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkKzTWM2OD1{ND61PEBvVQ>? MkfOV2FPT0WU
NBsusSR NYPDZppxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH73RVRKSzVyPUK0MlYhdk1? NXzXUZdrW0GQR1XS
CTB-1 Mn3HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTJ2Lk[3JI5O NH\OVnFUSU6JRWK=
FTC-133 M1XPc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPoTWM2OD1{NT6xJI5O Mmn5V2FPT0WU
MOLT-4 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYTJR|UxRTJ3LkGyJI5O MX;TRW5ITVJ?
HO-1-N-1 M2O5OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3FTWM2OD1{NT6xOUBvVQ>? M1SzUnNCVkeHUh?=
ES3 NF75PWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPWdmRKSzVyPUK1MlIzKG6P M2jDUXNCVkeHUh?=
TI-73 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIXrdIFKSzVyPUK1MlI5KG6P NXL0W2Y{W0GQR1XS
MPP-89 NFvYWXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHq4NVhKSzVyPUK1MlMzKG6P MmDSV2FPT0WU
KYSE-150 NWfSUlA6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTJ3Lki5JI5O MXrTRW5ITVJ?
LXF-289 MmTrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2Ow[WlEPTB;Mk[uNFQhdk1? NWriR2c6W0GQR1XS
SK-LU-1 NWryXJRsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTJ4LkG3JI5O MYnTRW5ITVJ?
HOP-92 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\DTWM2OD1{Nj60PEBvVQ>? Mn65V2FPT0WU
HuO9 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjyV3lNUUN3ME2yOk44PiCwTR?= M3LteHNCVkeHUh?=
SW962 MmDhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTJ4Lke2JI5O NHWzNGtUSU6JRWK=
RS4-11 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;jV5BKSzVyPUK2MlkyKG6P MlfMV2FPT0WU
NCI-H292 NEe3blRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHroOphKSzVyPUK3JI5O M4D2SXNCVkeHUh?=
DB M2rjOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TjdWlEPTB;MkeuN|Yhdk1? NUC5V4xIW0GQR1XS
SW1088 M1;zNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUDJR|UxRTJ6LkK5JI5O M4fFd3NCVkeHUh?=
A204 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPjTWM2OD1{OD60O{BvVQ>? NUfWNnAxW0GQR1XS
A3-KAW M{n1XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUfzW2pHUUN3ME2yPE43PCCwTR?= MX3TRW5ITVJ?
MV-4-11 NGXJZVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWW3cpM6UUN3ME2yPE44KG6P NFXHT|RUSU6JRWK=
ES1 M1r3b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmS0TWM2OD1{OD64OEBvVQ>? NGLibYdUSU6JRWK=
ONS-76 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGH2XFhKSzVyPUK5MlA2KG6P MV;TRW5ITVJ?
D-263MG NVS5dYcxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvqZVdNUUN3ME2yPU4{PSCwTR?= Ml[5V2FPT0WU
U-2-OS NV\nUo1mT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M370RWlEPTB;MkmuOUBvVQ>? NWrZVGY2W0GQR1XS
T98G M3;ZV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXn5e4NJUUN3ME2yPU45QCCwTR?= MVvTRW5ITVJ?
GI-ME-N MnrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTJ7LkmxJI5O M1q1RXNCVkeHUh?=
BHT-101 M1jES2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLONYpKSzVyPUOwMlA2KG6P M2jsRnNCVkeHUh?=
NOS-1 NV7sPVVIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTNyLkGyJI5O NGXjRZZUSU6JRWK=
AsPC-1 MmTUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkizTWM2OD1|MD6yJI5O NVqyN3VrW0GQR1XS
QIMR-WIL MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTNyLk[gcm0> MYXTRW5ITVJ?
JVM-3 MnnmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTNyLkizJI5O MnfJV2FPT0WU
KU-19-19 M3fkSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRTNzLkGzJI5O MVHTRW5ITVJ?
OVCAR-8 MnK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYO3dXhyUUN3ME2zNU4zPiCwTR?= NVX4UnJxW0GQR1XS
BEN NFfhXWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrmTWM2OD1|MT62N{BvVQ>? M17rUHNCVkeHUh?=
BE-13 NUXzb|lWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIrENpNKSzVyPUOxMlgzKG6P NW\aOnRIW0GQR1XS
EW-18 NXe1U41tT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWf1dndQUUN3ME2zNU45PiCwTR?= NIjoW2VUSU6JRWK=
ECC10 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWOwNnAxUUN3ME2zNU46PSCwTR?= NHzCbGdUSU6JRWK=
CTV-1 MlfkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmD0TWM2OD1|Mj64NkBvVQ>? NWfs[HZ5W0GQR1XS
COLO-800 M1jpWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFG3UldKSzVyPUOyMlkzKG6P NG\GNVhUSU6JRWK=
A2058 MlvnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXTJR|UxRTN|LkK1JI5O NV\HUnp1W0GQR1XS
VM-CUB-1 MorYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDqVmlLUUN3ME2zN{41OyCwTR?= NViybWo3W0GQR1XS
Ca9-22 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTN|LkW1JI5O M1i4enNCVkeHUh?=
COLO-684 M3Tsbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTN|LkW4JI5O MUHTRW5ITVJ?
RPMI-8226 NFnyOJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkP3TWM2OD1|Mz64NkBvVQ>? M1y2XnNCVkeHUh?=
SK-NEP-1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGP2fYlKSzVyPUO0MlE2KG6P MnnRV2FPT0WU
Becker M2LsPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XTVWlEPTB;M{SuNlEhdk1? NITyTJNUSU6JRWK=
NCI-H28 M{TURWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{O1XWlEPTB;M{SuOFQhdk1? NYfrN5p1W0GQR1XS
CAL-120 NXv0SYVuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoKwTWM2OD1|ND63NkBvVQ>? M1;DR3NCVkeHUh?=
MDA-MB-157 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnKxTWM2OD1|NT60NUBvVQ>? MULTRW5ITVJ?
OVCAR-5 MmTJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHSeoxKSzVyPUO1MlQ4KG6P NYnSUVAxW0GQR1XS
LAMA-84 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXHHbYlCUUN3ME2zOU45PyCwTR?= M2jNOXNCVkeHUh?=
CAKI-1 NXPJO2VUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTN4LkSzJI5O NWjwSm5LW0GQR1XS
Daoy NFnye4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PsbGlEPTB;M{[uO{BvVQ>? NH;heWFUSU6JRWK=
CAL-62 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4C1bWlEPTB;M{[uPFYhdk1? Ml;4V2FPT0WU
8-MG-BA M3Lncmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{nQemlEPTB;M{euNlUhdk1? M4TucHNCVkeHUh?=
8505C NGHabGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PkcGlEPTB;M{euOVEhdk1? NFrRRmhUSU6JRWK=
LNCaP-Clone-FGC M4L0Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{n3WWlEPTB;M{euOVkhdk1? NIXV[HdUSU6JRWK=
CAL-39 NHK1TlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIKxcmRKSzVyPUO3Mlkhdk1? NWTLZ3VwW0GQR1XS
MN-60 NEm4fYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPLV3l4UUN3ME2zO{46PiCwTR?= MUjTRW5ITVJ?
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NCI-H1581 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3jm[WlEPTB;NkSuNFMhdk1? MlvFV2FPT0WU
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COLO-678 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7zTWM2OD1{LkizO|Y5KM7:TR?= NGLrVFlUSU6JRWK=
SK-N-DZ MonwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnn2TWM2OD1{Lki2N|gyKM7:TR?= M1zyTnNCVkeHUh?=
NCI-H82 MkK0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTJwOUCzOlkh|ryP M2jYdXNCVkeHUh?=
JVM-2 M2HaVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTNwMEOxPFgh|ryP M2TGOXNCVkeHUh?=
SW1116 MlvWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnqTWM2OD1|LkC1OFEyKM7:TR?= Mn25V2FPT0WU
MDA-MB-453 NXK1[|dyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTNwMUC0N|kh|ryP M{\i[3NCVkeHUh?=
Calu-6 M4\yN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrDV3REUUN3ME2zMlE6QTdizszN NUXLWo9zW0GQR1XS
SHP-77 NF:4ZoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXPTWM2OD1|LkWyPEDPxE1? MXTTRW5ITVJ?
Capan-2 NFPXUYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTSfFBKSzVyPUSuN|I2QDFizszN M3PvSXNCVkeHUh?=
SW948 NH7vTItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7WNlVlUUN3ME20Mlc1Pzd7IN88US=> NWSyfnBPW0GQR1XS
HDLM-2 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTVwMEe3NlUh|ryP M13rR3NCVkeHUh?=
LAN-6 MkDvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzuZoU4UUN3ME22MlIyPDl3IN88US=> M2C2ZXNCVkeHUh?=
LU-135 MlTUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moi5TWM2OD14LkSzNFc4KM7:TR?= NXz6eW0{W0GQR1XS
T84 NFm2U5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfXe5d[UUN3ME22Mlk5PjRizszN MmXqV2FPT0WU
CAPAN-1 Mn7OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jSbWlEPTB;Nz62NlI{OyEQvF2= NVvxRWhWW0GQR1XS
SW1417 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYTJR|UxRTdwOUG3N|Eh|ryP MlzYV2FPT0WU
BALL-1 MlHUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmr5TWM2OD16LkWwOFA6KM7:TR?= NHnTO2tUSU6JRWK=
HT-29 NVXrXGZwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;QRZJKSzVyPUmuNFc2QTlizszN NGHYSIZUSU6JRWK=
C3A MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nv[2lEPTB;OT64PFM6PCEQvF2= MVPTRW5ITVJ?
NCI-H1993 NUnCVIdVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTMd4tKSzVyPUGwMlUxQDFizszN M3j5dnNCVkeHUh?=
SK-MEL-1 NW\pcFZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPKNIJEUUN3ME2xNU43Ojh7IN88US=> NHnGWHpUSU6JRWK=
DU-145 M{XrW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rLcWlEPTB;MUSuOVA2OiEQvF2= NHyyUGFUSU6JRWK=
KP-N-YN MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3FTWM2OD1zND61NVA{KM7:TR?= NH7LdYRUSU6JRWK=
CCRF-CEM M4GwcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrQR4dKSzVyPUG0Mlc5ODlizszN MX7TRW5ITVJ?
ZR-75-30 NXLwT2FiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3P4U2lEPTB;MU[uN|MxOyEQvF2= MWrTRW5ITVJ?
A673 NIrlUIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTJyLkW1NFch|ryP NV\QTHJ1W0GQR1XS
K-562 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHn6doRKSzVyPUK4MlQyQDNizszN MWHTRW5ITVJ?

... 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

Molarity Calculator

Molarity Calculator

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

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

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

Dilution Calculator

Dilution Calculator

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

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

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

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

The Serial Dilution Calculator Equation

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Molecular Weight Calculator

Molecular Weight Calculator

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

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03373903 Active not recruiting Respiratory Tract Infections Restorbio Inc. November 15 2017 Phase 2
NCT03373903 Active not recruiting Respiratory Tract Infections Restorbio Inc. November 15 2017 Phase 2
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01717898 Terminated Castrate-resistant Prostate Cancer Charles Ryan|Novartis Pharmaceuticals|University of California San Francisco January 31 2013 Phase 1|Phase 2
NCT01717898 Terminated Castrate-resistant Prostate Cancer Charles Ryan|Novartis Pharmaceuticals|University of California San Francisco January 31 2013 Phase 1|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.

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID