Dactolisib (BEZ235, NVP-BEZ235)

Catalog No.S1009

Dactolisib (BEZ235, NVP-BEZ235) Chemical Structure

Molecular Weight(MW): 469.55

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell.

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Cited by 84 Publications

11 Customer Reviews

  • Level of phospho-proteins in RTK and PI3K–Akt–mTOR pathways in treated tumours, detected with western blot.

    Nature, 2017, 728-732. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

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

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

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

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

     

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

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

     

     

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

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

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

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

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

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

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

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

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

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

     

     

     

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

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

     

     

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

  •  

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

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

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

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

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei M3nNU2FvfGmvaXPyc4Jq[WxiQYPzZZk> NX;wbHNsOThiaB?= MXrEUXNQ NEDQe3dCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP M37EdFI1QDB3OUS2
MCF7 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiwMlAyNTFyMDFOwG0> NYqwbHFZPDhiaB?= M1vDUWROW09? NICyeJBKSzVyPUCuO|Mh|ryP MV:yN|g4OTlyNB?=
HCT116 NUDaUXlqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXywMlAyNTFyMDFOwG0> NFjS[nM1QCCq NWLPZnNqTE2VTx?= MXrJR|UxRTFwMU[g{txO NV3RemFIOjN6N{G5NFQ>
U87MG MoPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTCNE4xOS1zMECg{txO MoPZOFghcA>? M2q1c2ROW09? MU\JR|UxRTFwM{Kg{txO NEnhOm8zOzh5MUmwOC=>
HBC4 NYrhUmFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXqeldmOC5yMT2xNFAh|ryP MXu0PEBp Mof6UI9oKEeLNUC9MVgvPjFiTR?= MUCyNlM{PjJ2Nh?=
BSY1 M2HkbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV:wMlAyNTFyMDFOwG0> NWjCSHhmPDhiaB?= MmfiUI9oKEeLNUC9MVgvPDhiTR?= MkXFNlI{OzZ{NE[=
HBC5 NXzWcnB5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHoS|JWOC5yMT2xNFAh|ryP M4ex[|Q5KGh? MW\Mc4chT0l3ME2tO{45PyCP M2LxblIzOzN4MkS2
MCF7 NF3h[5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHYTWExNjBzLUGwNEDPxE1? NVmye2g2PDhiaB?= MkXMUI9oKEeLNUC9MVgvOTZiTR?= NEPoS5kzOjN|NkK0Oi=>
MDA-MB-231 MnvHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHqbIRJOC5yMT2xNFAh|ryP NV62WWhpPDhiaB?= NYCwXZhuVG:pIFfJOVA:NThwMEmgUS=> NHSwOnYzOjN|NkK0Oi=>
U251 NGnlZXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHCNE4xOS1zMECg{txO NHTIUJo1QCCq MX\Mc4chT0l3ME2tO{43PiCP MVqyNlM{PjJ2Nh?=
SF268 NIfjPHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nGOVAvODFvMUCwJO69VQ>? M1zJfFQ5KGh? NF:2TWhNd2diR1m1NF0uPy57MjDN MmLiNlI{OzZ{NE[=
SF295 MkXuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\NUVAvODFvMUCwJO69VQ>? NIDkTWg1QCCq M4D1N2xw\yCJSUWwQU05NjNzIF2= Mn\wNlI{OzZ{NE[=
SF539 M3u2[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHTfW4xNjBzLUGwNEDPxE1? MmjKOFghcA>? NITj[W1Nd2diR1m1NF0uQC53OTDN NHnMWpozOjN|NkK0Oi=>
SNB75 MnnPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjLfodUOC5yMT2xNFAh|ryP MknmOFghcA>? NX7DTVdPVG:pIFfJOVA:NThwNUigUS=> NFHnTlczOjN|NkK0Oi=>
SNB78 M3\RRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV:wMlAyNTFyMDFOwG0> M{HufVQ5KGh? NEf2Z5NNd2diR1m1NF0uQC54NTDN M{[5dlIzOzN4MkS2
HCC2998 MmLSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHr1OXMxNjBzLUGwNEDPxE1? NVf4Voo6PDhiaB?= M3yxbGxw\yCJSUWwQU05NjB3IF2= Mn\PNlI{OzZ{NE[=
KM12 M3X1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHLmZ4kxNjBzLUGwNEDPxE1? MkTKOFghcA>? M1;mRmxw\yCJSUWwQU04NjV2IF2= NFTEdZgzOjN|NkK0Oi=>
HT-29 NWDDNoY2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkjONE4xOS1zMECg{txO MlzPOFghcA>? M2\jXWxw\yCJSUWwQU04Njd3IF2= MUOyNlM{PjJ2Nh?=
HCT15 NETse2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHLUWpGOC5yMT2xNFAh|ryP Mk\IOFghcA>? NGi5SohNd2diR1m1NF0uQC5yMzDN NGSxWnIzOjN|NkK0Oi=>
HCT116 NHvtXldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPiNE4xOS1zMECg{txO Mn7vOFghcA>? NHPYXpBNd2diR1m1NF0uPy54MTDN M3u5N|IzOzN4MkS2
NCI-H23 NFzCS2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17TeVAvODFvMUCwJO69VQ>? M1ToXlQ5KGh? NUXi[ZNEVG:pIFfJOVA:NTdwNkSgUS=> MViyNlM{PjJ2Nh?=
NCI-H226 MlHUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn7ONE4xOS1zMECg{txO MlzMOFghcA>? MWjMc4chT0l3ME2tPE41PCCP NGjWbIkzOjN|NkK0Oi=>
NCI-H522 NUTqV5k5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnLrNE4xOS1zMECg{txO MYi0PEBp NYfJUHZ3VG:pIFfJOVA:NThwNEWgUS=> NE\UflMzOjN|NkK0Oi=>
NCI-H438 MnP6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV[xbIJDOC5yMT2xNFAh|ryP NVziWVZJPDhiaB?= M{LXV2xw\yCJSUWwQU05NjFzIF2= NGTIfFkzOjN|NkK0Oi=>
A549 NF2zVWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfCZWtEOC5yMT2xNFAh|ryP MmL4OFghcA>? M1LDTmxw\yCJSUWwQU05NjB5IF2= MYCyNlM{PjJ2Nh?=
DMS273 NFPncJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjZc4k1OC5yMT2xNFAh|ryP NYXGZXhYPDhiaB?= Mk[5UI9oKEeLNUC9MVcvQDBiTR?= NYrPW2hHOjJ|M{[yOFY>
DMS114 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn36NE4xOS1zMECg{txO MlXiOFghcA>? M4PkU2xw\yCJSUWwQU05NjN7IF2= MkXENlI{OzZ{NE[=
LOXIMVI NGDKd49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XRNVAvODFvMUCwJO69VQ>? M3PJSVQ5KGh? MlHYUI9oKEeLNUC9MVgvPjZiTR?= NFXjZ3EzOjN|NkK0Oi=>
OVCAR3 Mnn0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3TcHcxNjBzLUGwNEDPxE1? NGTjTJE1QCCq NYGwOJF[VG:pIFfJOVA:NThwMUegUS=> Mn30NlI{OzZ{NE[=
OVCAR4 NGnBd5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLMeWYxNjBzLUGwNEDPxE1? NXjRT|QxPDhiaB?= NILLc3ZNd2diR1m1NF0uQC53ODDN MoDFNlI{OzZ{NE[=
OVCAR5 NFHlW2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4n0OFAvODFvMUCwJO69VQ>? M1ryclQ5KGh? MnPhUI9oKEeLNUC9MVcvPTdiTR?= NELsPHAzOjN|NkK0Oi=>
OVCAR8 MnTUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;5PJhOOC5yMT2xNFAh|ryP MUK0PEBp MVvMc4chT0l3ME2tO{45PCCP NUfKT2FkOjJ|M{[yOFY>
SKOV3 MofLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXuwMlAyNTFyMDFOwG0> M3zVTFQ5KGh? NIHvcopNd2diR1m1NF0uQC52MTDN MnzGNlI{OzZ{NE[=
RXF631L M2m4e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnBSWVWOC5yMT2xNFAh|ryP Ml3YOFghcA>? NW\ldWx{VG:pIFfJOVA:NThwMkGgUS=> NX71ZVB{OjJ|M{[yOFY>
ACHN NFjYeXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2DwW|AvODFvMUCwJO69VQ>? NYr5WZEzPDhiaB?= M2LCdmxw\yCJSUWwQU04Njl3IF2= MoW4NlI{OzZ{NE[=
St-4 NVT6e2JJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvWNE4xOS1zMECg{txO M1m0RlQ5KGh? NH2xTmlNd2diR1m1NF0uPy52NzDN MYOyNlM{PjJ2Nh?=
MKN1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzkWoExNjBzLUGwNEDPxE1? Mn35OFghcA>? M{LxSmxw\yCJSUWwQU05NjRzIF2= NVW1NIJVOjJ|M{[yOFY>
MKN7 NV7DN4pvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWH1WpY1OC5yMT2xNFAh|ryP M4PHU|Q5KGh? NHrrNpNNd2diR1m1NF0uPy54ODDN MnXONlI{OzZ{NE[=
MKN28 NGrsfFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1m5R|AvODFvMUCwJO69VQ>? MWS0PEBp M4nyUWxw\yCJSUWwQU04NjB5IF2= MnfBNlI{OzZ{NE[=
MKN45 NF3Xd|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXJS3UxNjBzLUGwNEDPxE1? M1qxOVQ5KGh? MYfMc4chT0l3ME2tPE4{PCCP NFLrR|YzOjN|NkK0Oi=>
MKN74 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3[zbVAvODFvMUCwJO69VQ>? MXq0PEBp NGnMXFJNd2diR1m1NF0uPy52MjDN M3zTflIzOzN4MkS2
DU145 NU\YRnRST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1f0TFAvODFvMUCwJO69VQ>? NILy[Gs1QCCq NV\kfmFrVG:pIFfJOVA:NThwMU[gUS=> NVyxR2h3OjJ|M{[yOFY>
PC3 MoKxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnH[2tDOC5yMT2xNFAh|ryP NXT4fYQzPDhiaB?= MVvMc4chT0l3ME2tPE43PiCP MVSyNlM{PjJ2Nh?=
Trypanosoma brucei brucei M2DQ[2Z2dmO2aX;uJGF{e2G7 M3\iZlIxOCCwTR?= MX6xNkBp MXHEUXNQ M3zQV2Rm[3KnYYPlJIlvKHCqb4PwbI91cWS7bDDpco9{cXSxbDDwbI9{eGijdHWgcIV3\Wx? M37L[VI1QDB3OUS2
Trypanosoma brucei brucei NVjjeHU4TnWwY4Tpc44hSXO|YYm= NHL5Oo0yQCCq NXG2cZJqTE2VTx?= NWnsU|dJUW6qaXLpeIlwdiCxZjDy[YNmeHSxcj3t[YRq[XSnZDDlcoRw[3m2b4Ppd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjD0doFve2[ncoLpckB2eHSja3W= MlfkNlQ5ODV7NE[=
Trypanosoma brucei brucei MXXGeY5kfGmxbjDBd5NigQ>? MWOyNFAhdk1? M3r1UVEzKGh? NGC2eIRFVVOR NG\DPXJG\m[nY4Sgc44he3CqaX7nc416dGWrbjDs[ZZmdA>? NIi1TmozPDhyNUm0Oi=>
Trypanosoma brucei brucei NFHaR3hHfW6ldHnvckBCe3OjeR?= MmH1NlAxKG6P NILxWnkyOiCq M1vJTWROW09? MoLkSYZn\WO2IH;uJJBpd3OyaHH0bYR6dGOqb3zpcoUhdGW4ZXy= NYfKZnkxOjR6MEW5OFY>
UM-UC-3 NF7CRVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTNzNTDwUS=> M3SxTnNCVkeHUh?=
SBC-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7HTWM2OD15NEKgdG0> M1izXXNCVkeHUh?=
MKN1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXnJR|UxRTJwODDuUS=> MnvjV2FPT0WU
NCI-H720 NWT2N2VrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1j5Z2lEPTB;Mz61O{BvVQ>? M{XRN3NCVkeHUh?=
BFTC-909 NY\GTWhUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;Vd21rUUN3ME2zMlcyKG6P MoniV2FPT0WU
BPH-1 M2OxN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnyWmxKSzVyPUSuO|Yhdk1? MnvOV2FPT0WU
PC-3 M1HEW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoHITWM2OD13LkC5JI5O M1XJb3NCVkeHUh?=
AN3-CA MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{XrSmlEPTB;NT61OkBvVQ>? NGPubllUSU6JRWK=
HN MnvnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHQZm5TUUN3ME21Mlk3KG6P M4DTTXNCVkeHUh?=
HCC2218 M3;iXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH;WSY5KSzVyPU[uOlEhdk1? MlO3V2FPT0WU
KP-4 NULpe2NuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4X5V2lEPTB;NzDuUS=> NEfGSoVUSU6JRWK=
LU-139 NXfK[4ZsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDTcVlKSzVyPUeuO|chdk1? NYXqepNZW0GQR1XS
ETK-1 NVHRT3ZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\BZnhNUUN3ME23Mlg5KG6P MmDaV2FPT0WU
Ramos-2G6-4C10 M{f4TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRThwNEmgcm0> MYnTRW5ITVJ?
MHH-PREB-1 M3\4WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH3PW2RKSzVyPUmuNVIhdk1? M3j3cnNCVkeHUh?=
DU-4475 NEf3c5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkT2TWM2OD17LkS0JI5O M2O0V3NCVkeHUh?=
NCI-H1666 M4Wyc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnBdIlLUUN3ME25MlcyKG6P MVjTRW5ITVJ?
CAMA-1 NVrROFRRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX[0cYFFUUN3ME25Mlghdk1? NVHGfVU6W0GQR1XS
TYK-nu M3PiSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rFSWlEPTB;OT65OEBvVQ>? NHLxNnRUSU6JRWK=
MFE-280 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn65TWM2OD17Lkm5JI5O MVPTRW5ITVJ?
A549 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTFyLkG0JI5O M2\WOnNCVkeHUh?=
769-P NWfYRmZjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHtWIFKSzVyPUGwMlQ1KG6P NHHOfoZUSU6JRWK=
L-363 Mo\nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjNbnRKSzVyPUGwMlY6KG6P NUnQbmxPW0GQR1XS
ES8 M2jYNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;OS2lEPTB;MUCuPUBvVQ>? MVHTRW5ITVJ?
PA-1 M2rLXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPLTWM2OD1zMT64NkBvVQ>? MWPTRW5ITVJ?
Mewo MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTFzLkm5JI5O MWTTRW5ITVJ?
HSC-3 NHjOem1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELFVpZKSzVyPUGyMlIyKG6P NWmwPZhqW0GQR1XS
H4 NIC1RmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\CcYdKSzVyPUGyMlY4KG6P MlLEV2FPT0WU
BB65-RCC MnzDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHXU21KSzVyPUGyMlczKG6P MUXTRW5ITVJ?
NCI-H1793 MkfCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjGbmtKSzVyPUGyMlgzKG6P M372TXNCVkeHUh?=
KARPAS-45 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{XncGlEPTB;MUOuOVEhdk1? NEnFUXRUSU6JRWK=
GCT NVPRW4F7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHQTWM2OD1zMz62PEBvVQ>? NXHufnNGW0GQR1XS
EoL-1 M2jRWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4S3dGlEPTB;MUOuPVMhdk1? NYHj[odFW0GQR1XS
LB2241-RCC MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF7WPIRKSzVyPUG0MlAyKG6P MmH1V2FPT0WU
ES5 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2H6VGlEPTB;MUSuO|Qhdk1? MlvvV2FPT0WU
LOXIMVI MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXXJR|UxRTF2Lkm5JI5O M4r3XHNCVkeHUh?=
COR-L105 MkDNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLuR|lKSzVyPUG1MlA1KG6P NGqxXHVUSU6JRWK=
P12-ICHIKAWA NF[xfndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NITuNJdKSzVyPUG1MlEhdk1? NGjhXWJUSU6JRWK=
CHL-1 M3XadWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HsUWlEPTB;MUWuOFUhdk1? NF;3fGxUSU6JRWK=
VMRC-RCZ NX7vOINIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTF3Lk[zJI5O Mnz2V2FPT0WU
HH MmOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXoPWZbUUN3ME2xOU44KG6P NHnB[3RUSU6JRWK=
NUGC-3 NHL5Z2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVXJR|UxRTF4LkO0JI5O NHTpem9USU6JRWK=
EGI-1 M3LmRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\FTYhKSzVyPUG2MlQ{KG6P MlX1V2FPT0WU
OS-RC-2 NEPPUZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnwTWM2OD1zNj60O{BvVQ>? M{\jVXNCVkeHUh?=
MOLT-16 MonuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;hcmlEPTB;MUeuNVUhdk1? NInwbGtUSU6JRWK=
NCI-H209 MlzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEm2T|dKSzVyPUG3MlI6KG6P MWPTRW5ITVJ?
697 NHPr[IdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvycIJKSzVyPUG3MlQ{KG6P MlLsV2FPT0WU
D-56MG M3jzVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTF5Lk[5JI5O M{fBdnNCVkeHUh?=
VA-ES-BJ NUTuZo1LT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3L4NmlEPTB;MUeuPFMhdk1? M2nXPHNCVkeHUh?=
EW-16 M2fnfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTF6LkC0JI5O M4DyeHNCVkeHUh?=
HGC-27 NW\vSYpET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDqV2FFUUN3ME2xPE4xPiCwTR?= NHWyb|FUSU6JRWK=
ES7 M2n5dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{j1bmlEPTB;MUiuNFkhdk1? NX\zUJBKW0GQR1XS
HuH-7 MlHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\OTWM2OD1zOD60JI5O NIjiWXRUSU6JRWK=
BCPAP NIDHS2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{fwVWlEPTB;MUiuOlUhdk1? Mor5V2FPT0WU
SW1710 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTGTWM2OD1zOD63NkBvVQ>? NE\WTFFUSU6JRWK=
IST-MEL1 NUXDW3M6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4TWZWlEPTB;MUiuO|chdk1? NIjuWYtUSU6JRWK=
SF295 MlPLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnW1TWM2OD1zOD65N{BvVQ>? MVPTRW5ITVJ?
RPMI-7951 NY\SdZJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;JZ2lEPTB;MUmuNlghdk1? M1fVW3NCVkeHUh?=
SF126 M{jEZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV[0S|EzUUN3ME2xPU41OSCwTR?= M2DVOXNCVkeHUh?=
GAMG M{DaOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFHOfnZKSzVyPUG5MlQ5KG6P NWL5VGtoW0GQR1XS
KNS-81-FD MnrlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTF7LkW0JI5O M2DNOHNCVkeHUh?=
RT-112 NUXnRXNuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYDJR|UxRTF7Lk[2JI5O MXLTRW5ITVJ?
DEL NW\HdZJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTJyLkS5JI5O Mk[3V2FPT0WU
CGTH-W-1 MkLyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWjWZoNCUUN3ME2yNE43OyCwTR?= NV74T|VIW0GQR1XS
HOS NWTiSXJST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFjmZphKSzVyPUKxMlA3KG6P MlHSV2FPT0WU
ES4 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjKT4ZKSzVyPUKxMlA5KG6P MnviV2FPT0WU
RXF393 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NInpR21KSzVyPUKxMlQ2KG6P NEW2NXNUSU6JRWK=
NCI-H2030 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3r2NGlEPTB;MkGuOVIhdk1? MWnTRW5ITVJ?
YH-13 MkHDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn21TWM2OD1{MT64PEBvVQ>? M{\sVXNCVkeHUh?=
HT-1080 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFO2V5RKSzVyPUKxMlk{KG6P M{\uZXNCVkeHUh?=
NCI-SNU-1 Mnq5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7ITWM2OD1{MT65OUBvVQ>? MorLV2FPT0WU
G-402 NG[2bmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTJ{LkG2JI5O MVHTRW5ITVJ?
786-0 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGn4fFhKSzVyPUKyMlI6KG6P MmXZV2FPT0WU
ME-180 NEnHOmFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzSTWM2OD1{Mj60N{BvVQ>? NISzZphUSU6JRWK=
NB69 MkDmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M32zTWlEPTB;MkKuOVMhdk1? Mn7XV2FPT0WU
J-RT3-T3-5 MmLyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\ucFlKSzVyPUKyMlk3KG6P MX3TRW5ITVJ?
TGBC1TKB NXTEVIpbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M362fmlEPTB;MkOuNFUhdk1? MkjaV2FPT0WU
SW780 M3K0cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTJ|LkGzJI5O MWrTRW5ITVJ?
MG-63 M{TPSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWLJR|UxRTJ|LkS1JI5O NULGbm1YW0GQR1XS
BV-173 M3TpcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1j5Z2lEPTB;MkOuPFchdk1? NFq1T4RUSU6JRWK=
CAL-51 M{fMPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnkTWM2OD1{Mz64PUBvVQ>? MWLTRW5ITVJ?
A375 MmezS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LlbWlEPTB;MkOuPVMhdk1? NInwWIxUSU6JRWK=
MEL-HO MmDjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTJ2LkC0JI5O MUTTRW5ITVJ?
EFO-27 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfDNY9KSzVyPUK0MlM{KG6P NEH1W3ZUSU6JRWK=
Hs-578-T M1L3SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTsN3BiUUN3ME2yOE42QCCwTR?= MkLBV2FPT0WU
NBsusSR M3fpPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXzW|VKSzVyPUK0MlYhdk1? M4T1THNCVkeHUh?=
CTB-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTJ2Lk[3JI5O MkLOV2FPT0WU
FTC-133 NH;PcGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTJ3LkGgcm0> M4LqS3NCVkeHUh?=
MOLT-4 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{m2fmlEPTB;MkWuNVIhdk1? MYDTRW5ITVJ?
HO-1-N-1 NYTtWJVVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3:0RmlEPTB;MkWuNVUhdk1? NVL1R|B4W0GQR1XS
ES3 M2nWfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3LSGRGUUN3ME2yOU4zOiCwTR?= MUHTRW5ITVJ?
TI-73 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTJ3LkK4JI5O M1rGUHNCVkeHUh?=
MPP-89 M{TzUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfoTWM2OD1{NT6zNkBvVQ>? MkHCV2FPT0WU
KYSE-150 NX7zOYxsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF7xNpNKSzVyPUK1Mlg6KG6P MYfTRW5ITVJ?
LXF-289 NXTBWoxMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTYWFVNUUN3ME2yOk4xPCCwTR?= MXzTRW5ITVJ?
SK-LU-1 MmfGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\lXmtKSzVyPUK2MlE4KG6P M{\NbnNCVkeHUh?=
HOP-92 M133c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTJ4LkS4JI5O NHfjTmFUSU6JRWK=
HuO9 M3PLZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnv4TWM2OD1{Nj63OkBvVQ>? NH76S2lUSU6JRWK=
SW962 MnHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPjWndKSzVyPUK2Mlc3KG6P NGiwR|FUSU6JRWK=
RS4-11 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoD2TWM2OD1{Nj65NUBvVQ>? NITBSGpUSU6JRWK=
NCI-H292 NULuVYxpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLoTWM2OD1{NzDuUS=> MVvTRW5ITVJ?
DB MnvOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXLreHJSUUN3ME2yO{4{PiCwTR?= MXzTRW5ITVJ?
SW1088 MlT2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4n4VGlEPTB;MkiuNlkhdk1? NFrENnVUSU6JRWK=
A204 NVflbFBbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT5XVlKSzVyPUK4MlQ4KG6P MWPTRW5ITVJ?
A3-KAW MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTJ6Lk[0JI5O MVnTRW5ITVJ?
MV-4-11 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTJ6Lkegcm0> MWTTRW5ITVJ?
ES1 MmflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXmySYRDUUN3ME2yPE45PCCwTR?= NWDhZottW0GQR1XS
ONS-76 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVjJR|UxRTJ7LkC1JI5O MXnTRW5ITVJ?
D-263MG NVnsZ4tET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTJ7LkO1JI5O NH3QeVFUSU6JRWK=
U-2-OS MoTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTTTWM2OD1{OT61JI5O MVzTRW5ITVJ?
T98G M1XrbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;1fYR1UUN3ME2yPU45QCCwTR?= NGDudGdUSU6JRWK=
GI-ME-N MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17weWlEPTB;MkmuPVEhdk1? MlrIV2FPT0WU
BHT-101 NWLKXGlxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY\mR2hDUUN3ME2zNE4xPSCwTR?= MWrTRW5ITVJ?
NOS-1 MnrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NInGWo1KSzVyPUOwMlEzKG6P MWXTRW5ITVJ?
AsPC-1 M4nHTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYeyT5NmUUN3ME2zNE4zKG6P M4O0bXNCVkeHUh?=
QIMR-WIL MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVzZT401UUN3ME2zNE43KG6P MY\TRW5ITVJ?
JVM-3 NFe2cHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;RTWM2OD1|MD64N{BvVQ>? NIrwNY1USU6JRWK=
KU-19-19 NFvGO4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEm1XmhKSzVyPUOxMlE{KG6P NHSzZnNUSU6JRWK=
OVCAR-8 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HvemlEPTB;M{GuNlYhdk1? MlvyV2FPT0WU
BEN MomwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFznV3ZKSzVyPUOxMlY{KG6P M4eybnNCVkeHUh?=
BE-13 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHrsSYlKSzVyPUOxMlgzKG6P NUL0T4lHW0GQR1XS
EW-18 NI\0c|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX30fHF4UUN3ME2zNU45PiCwTR?= NUjqRVZWW0GQR1XS
ECC10 M1rhe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7UfWVpUUN3ME2zNU46PSCwTR?= MmTzV2FPT0WU
CTV-1 NVf1NodbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jrRmlEPTB;M{KuPFIhdk1? M1LGd3NCVkeHUh?=
COLO-800 NETwZWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnDc2dYUUN3ME2zNk46OiCwTR?= NXv2eFVvW0GQR1XS
A2058 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrSTWM2OD1|Mz6yOUBvVQ>? MVvTRW5ITVJ?
VM-CUB-1 Mo\NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrGTGZQUUN3ME2zN{41OyCwTR?= NECwVYNUSU6JRWK=
Ca9-22 NYrTWVJiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnwN5FKSzVyPUOzMlU2KG6P NH3pN4FUSU6JRWK=
COLO-684 MmPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljGTWM2OD1|Mz61PEBvVQ>? MXHTRW5ITVJ?
RPMI-8226 NFHzN|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIP1dm1KSzVyPUOzMlgzKG6P NFS4SHJUSU6JRWK=
SK-NEP-1 MoPYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fXfGlEPTB;M{SuNVUhdk1? NIHzVHRUSU6JRWK=
Becker M1TQSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXrJR|UxRTN2LkKxJI5O NHPsWVRUSU6JRWK=
NCI-H28 NWjWSYtMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPWXGpKSzVyPUO0MlQ1KG6P NHvzfY9USU6JRWK=
CAL-120 NYX2UIxYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnDTWM2OD1|ND63NkBvVQ>? MkewV2FPT0WU
MDA-MB-157 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjJR|UxRTN3LkSxJI5O M1PpSnNCVkeHUh?=
OVCAR-5 M1PhXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTlc|dPUUN3ME2zOU41PyCwTR?= NWPEU4tCW0GQR1XS
LAMA-84 NV;0OHZjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTNTWM2OD1|NT64O{BvVQ>? MVXTRW5ITVJ?
CAKI-1 M3jhNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;TVpFKSzVyPUO2MlQ{KG6P MnfRV2FPT0WU
Daoy NH;2cHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NInUeotKSzVyPUO2Mlchdk1? MWTTRW5ITVJ?
CAL-62 Mlq3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEfCTmlKSzVyPUO2Mlg3KG6P M1q3fXNCVkeHUh?=
8-MG-BA NXPLT4g{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjYfZFjUUN3ME2zO{4zPSCwTR?= MWLTRW5ITVJ?
8505C MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4fsZmlEPTB;M{euOVEhdk1? MVrTRW5ITVJ?
LNCaP-Clone-FGC Mo\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTN5LkW5JI5O NGO0VmFUSU6JRWK=
CAL-39 NXvYeIUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPMOI1[UUN3ME2zO{46KG6P NHyw[3lUSU6JRWK=
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C8166 NFi1PHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3sbXdKSzVyPUKuOlM{QTJizszN M{TjXHNCVkeHUh?=
COLO-678 M1LMVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjX[Y5xUUN3ME2yMlg{PzZ6IN88US=> NH;MdG5USU6JRWK=
SK-N-DZ NXznU4R5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTJwOE[zPFEh|ryP NFPy[VVUSU6JRWK=
NCI-H82 MknlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mni5TWM2OD1{LkmwN|Y6KM7:TR?= MWnTRW5ITVJ?
JVM-2 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVnJR|UxRTNwMEOxPFgh|ryP NHvie2pUSU6JRWK=
SW1116 Mn:1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrwTWM2OD1|LkC1OFEyKM7:TR?= NWTXcWdrW0GQR1XS
MDA-MB-453 MnLpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDYZW9KSzVyPUOuNVA1OzlizszN MY\TRW5ITVJ?
Calu-6 M2\HWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVHJTnBRUUN3ME2zMlE6QTdizszN M2C4R3NCVkeHUh?=
SHP-77 M1vCZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTNwNUK4JO69VQ>? NUT1VVF6W0GQR1XS
Capan-2 MnXwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrjS2lKSzVyPUSuN|I2QDFizszN MXvTRW5ITVJ?
SW948 M2\vVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUnDTG41UUN3ME20Mlc1Pzd7IN88US=> MYLTRW5ITVJ?
HDLM-2 M{PyRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\GXnZKSzVyPUWuNFc4OjVizszN NWXWNXc6W0GQR1XS
LAN-6 NX76ZmtQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTZwMkG0PVUh|ryP NWT2TlJnW0GQR1XS
LU-135 NFzndYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2D0T2lEPTB;Nj60N|A4PyEQvF2= MUfTRW5ITVJ?
T84 MknOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TVTGlEPTB;Nj65PFY1KM7:TR?= MkmzV2FPT0WU
CAPAN-1 NV;afnZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{XhZ2lEPTB;Nz62NlI{OyEQvF2= NFTCfWNUSU6JRWK=
SW1417 M{\0W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTnZXZbUUN3ME23MlkyPzNzIN88US=> NWfrZXd[W0GQR1XS
BALL-1 M2[wNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlj5TWM2OD16LkWwOFA6KM7:TR?= NXTCN4pTW0GQR1XS
HT-29 NYT3clB3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTlwMEe1PVkh|ryP M{\xfHNCVkeHUh?=
C3A NY\rTZRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHBTWM2OD17Lki4N|k1KM7:TR?= MoGwV2FPT0WU
NCI-H1993 NYDqR4ZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnhTWM2OD1zMD61NFgyKM7:TR?= NIfFW4RUSU6JRWK=
SK-MEL-1 NFnwfo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfGTWM2OD1zMT62Nlg6KM7:TR?= MVHTRW5ITVJ?
DU-145 NHfLdVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDOTWM2OD1zND61NFUzKM7:TR?= M2PPeXNCVkeHUh?=
KP-N-YN MmW2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPjbFFYUUN3ME2xOE42OTB|IN88US=> NVPvb|dwW0GQR1XS
CCRF-CEM M{\v[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jBUGlEPTB;MUSuO|gxQSEQvF2= Ml;QV2FPT0WU
ZR-75-30 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDUVWRKSzVyPUG2MlM{ODNizszN MYPTRW5ITVJ?
A673 MkPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGrTSXpKSzVyPUKwMlU2ODdizszN MUfTRW5ITVJ?
K-562 NWLWWWZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV22WlduUUN3ME2yPE41OTh|IN88US=> NUX4TJBXW0GQR1XS

... Click to View More Cell Line Experimental Data
In vivo BEZ235 induces regression of the tumors (69%) without statistically significant effect on body weight gain. Altogether, these preliminary in vivo efficacy results show that BEZ235 causes disease stasis when administered orally as a single agent and can enhance the efficacy of other anticancer agents when used in combination studies. [1]

Protocol

Kinase Assay:

[1]
+ Expand

In vitro Protein Kinase, PI3K, and mTOR Assays:

PI3Kα, β, and δ proteins are composed of the iSH2 domain of p85 NH2-terminally fused to the full-length protein p110 protein, with the exception of α that also does not contain the last 20 amino acids. PI3Kγ is produced as full-length protein deleted for its first 144 amino acids. All constructs are fused to a COOH-terminal His tag for convenient purification and then cloned into the pBlue-Bac4.5 (for α, β, and δ isoforms) or pVL1393 (for γ isoform) plasmids. The different vectors are then cotransfected with BaculoGold WT genomic DNA using methods recommended by the vendor for production of the respective recombinant baculoviruses and proteins. BEZ235 are tested for their activity against PI3K using a Kinase-Glo assay. The kinase reaction is done in 384-well black plate. Each well is loaded with 50 μL of test items (in 90% DMSO) and 5 μL reaction buffer containing 10 μg/mL PI substrate (l-α-phosphatidylinositol; Avanti Polar Lipids; prepared in 3% octyl-glucoside) and the PI3K proteins (10, 25, 10, and 150 nM of p110α, p110β, p110δ, and p110γ, respectively) are then added to it. The reaction is started by the addition of 5 μL of 1 μM ATP prepared in the reaction buffer and is incubated for either 60 (for p110α, p110β, and p110δ) or 120 min (for p110γ). It is terminated by the addition of 10 μL Kinase-Glo buffer. The plates are then read in a Synergy 2 reader for luminescence detection.
Cell Research:

[2]
+ Expand
  • Cell lines: HCT116, DLD-1 and SW480 cells
  • Concentrations: 0-1 μM
  • Incubation Time: 48 hours
  • Method:

    The human CRC cell lines, HCT116 (PIK3CA mutant; kinase domain at H1047R), DLD-1 (PIK3CA mutant; helical domain at E545K), and SW480 (PIK3CA wild-type) and isogenic DLD-1 PIK3CA mutant as well as wild-type cells are maintained in DMEM with 10% FBS and 1 × Penicillin/Streptomycin. Cells are plated at different initial densities (HCT116: 3 × 103 cells/well, DLD-1: 5.5 × 103 cells/well, SW480: 4.5 × 103 cells/well, DLD-1 PIK3CA mutant: 7 × 103 cells/well, and DLD-1 PIK3CA wild-type: 9 × 103 cells/well) to account for differential growth kinetics. After 16 hours, cells are incubated with increasing concentrations of BEZ235, and the drug-containing growth medium is changed every 24 hours. Cell viability is assessed 16 hours after the initial plating and 48 hours after initiation of drug treatment using the colorimetric MTS assay CellTiter 96® AQueous One Solution Cell Proliferation Assay, as per the manufacturer's instructions. Cell viability after drug treatment is normalized to that of untreated cells also grown for 48 hours. For western blot analysis, cells are plated with zero or maximum inhibitory dose (500 nM) BEZ235 for 2, 6, 24, or 48 hours.


    (Only for Reference)
Animal Research:

[1]
+ Expand
  • Animal Models: Female Harlan athymic nude mice
  • Formulation: NMP/polyethylene glycol 300 (10/90, v/v)
  • Dosages: 45 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMF 18 mg/mL warmed (38.33 mM)
DMSO 0.01 mg/mL (0.02 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
NMP+polyethylene glycol 300 (10+90, v+v)
For best results, use promptly after mixing. 		30 mg/mL

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

Chemical Information

Molecular Weight 469.55
Formula

C30H23N5O
CAS No. 915019-65-7
Storage powder
in solvent
Synonyms N/A

Bio Calculators

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Clinical Trial Information

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

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

    With difficulties in dissolving BEZ235, How can I improve its solubility?

  • Answer:

    For in vivo study, we suggest the vehicle solution NMP/polyethylene glycol 300 (10/90, v/v). Please dissolve BEZ235 in NMP as more as possible. You can sonicate and warm it in water bath for a while. Then dilute with PEG 300.

selleck catalog

PI3K Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID