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 M4PvO2FvfGmvaXPyc4Jq[WxiQYPzZZk> NWrVclJrOThiaB?= MV7EUXNQ NFLQRlVCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP M3H3TlI1QDB3OUS2
MCF7 M2HN[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYTaPVRVOC5yMT2xNFAh|ryP M3vSVFQ5KGh? MmfFSG1UVw>? Mn;lTWM2OD1yLkezJO69VQ>? NIj6bI0zOzh5MUmwOC=>
HCT116 Mkf0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHtSlQxNjBzLUGwNEDPxE1? M3rCbVQ5KGh? NHXHdXlFVVOR Mn\HTWM2OD1zLkG2JO69VQ>? NIPuXYIzOzh5MUmwOC=>
U87MG M4jOWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVywMlAyNTFyMDFOwG0> MXu0PEBp NH:zO4pFVVOR NE\0elVKSzVyPUGuN|Ih|ryP Mn75NlM5PzF7MES=
HBC4 NGfHboNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPXV5cxNjBzLUGwNEDPxE1? NETp[no1QCCq NF3FVVBNd2diR1m1NF0uQC54MTDN M4C2[lIzOzN4MkS2
BSY1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjxPJoxOC5yMT2xNFAh|ryP MWi0PEBp MmnEUI9oKEeLNUC9MVgvPDhiTR?= NX;pO3p4OjJ|M{[yOFY>
HBC5 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTmNE4xOS1zMECg{txO NVPxWVNoPDhiaB?= MUjMc4chT0l3ME2tO{45PyCP M3PC[lIzOzN4MkS2
MCF7 M3W3fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDtboVZOC5yMT2xNFAh|ryP MYC0PEBp NYHYU4h6VG:pIFfJOVA:NThwMU[gUS=> Ml\WNlI{OzZ{NE[=
MDA-MB-231 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXWwMlAyNTFyMDFOwG0> M1zHOFQ5KGh? MW\Mc4chT0l3ME2tPE4xQSCP Ml7kNlI{OzZ{NE[=
U251 NIHEV3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnH4NE4xOS1zMECg{txO NX3NXYtvPDhiaB?= NXrWfIU{VG:pIFfJOVA:NTdwNk[gUS=> M2LSe|IzOzN4MkS2
SF268 M4jL[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4PObFAvODFvMUCwJO69VQ>? NWD5PYJjPDhiaB?= MYnMc4chT0l3ME2tO{46OiCP MnfvNlI{OzZ{NE[=
SF295 M2PweGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrS[Y1COC5yMT2xNFAh|ryP NFvmUZA1QCCq NFPocWpNd2diR1m1NF0uQC5|MTDN NV\WelBNOjJ|M{[yOFY>
SF539 NIiyVHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrVVYtmOC5yMT2xNFAh|ryP Mo\4OFghcA>? MVzMc4chT0l3ME2tPE42QSCP MUCyNlM{PjJ2Nh?=
SNB75 NYPhd2ozT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUniT|h5OC5yMT2xNFAh|ryP NIrI[Xo1QCCq MYjMc4chT0l3ME2tPE42QCCP MWKyNlM{PjJ2Nh?=
SNB78 NVjlfI5jT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHnNWE3OC5yMT2xNFAh|ryP MnXNOFghcA>? MkHCUI9oKEeLNUC9MVgvPjViTR?= NX;3U|cxOjJ|M{[yOFY>
HCC2998 M1GwcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3T0ZVAvODFvMUCwJO69VQ>? MlnLOFghcA>? MYjMc4chT0l3ME2tPE4xPSCP NILwdWkzOjN|NkK0Oi=>
KM12 MnrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWSwMlAyNTFyMDFOwG0> MUS0PEBp MlrEUI9oKEeLNUC9MVcvPTRiTR?= NULkVFBJOjJ|M{[yOFY>
HT-29 NIizUJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXuxU4tIOC5yMT2xNFAh|ryP M1fUVlQ5KGh? NH7zOVBNd2diR1m1NF0uPy55NTDN NEjGOpczOjN|NkK0Oi=>
HCT15 NVnUbXJWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorZNE4xOS1zMECg{txO NFrPO5M1QCCq MWTMc4chT0l3ME2tPE4xOyCP NVLZTlJUOjJ|M{[yOFY>
HCT116 M17tVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDvNE4xOS1zMECg{txO NW\Dc|FWPDhiaB?= MVPMc4chT0l3ME2tO{43OSCP NYT4UWxbOjJ|M{[yOFY>
NCI-H23 NH7FPFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnPUVgxNjBzLUGwNEDPxE1? NWjaXo1NPDhiaB?= MXrMc4chT0l3ME2tO{43PCCP NWewWXFmOjJ|M{[yOFY>
NCI-H226 NGXiW3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fw[FAvODFvMUCwJO69VQ>? NXjXe2ttPDhiaB?= NGfZS41Nd2diR1m1NF0uQC52NDDN NGf4R5QzOjN|NkK0Oi=>
NCI-H522 M3nhbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1n4OlAvODFvMUCwJO69VQ>? NEjpcnk1QCCq NGTYZohNd2diR1m1NF0uQC52NTDN NIfWWmkzOjN|NkK0Oi=>
NCI-H438 NX3OdHZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmX3NE4xOS1zMECg{txO M1TyTFQ5KGh? Ml7yUI9oKEeLNUC9MVgvOTFiTR?= NYTqfo5pOjJ|M{[yOFY>
A549 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiwMlAyNTFyMDFOwG0> NFHxUIg1QCCq M3X0S2xw\yCJSUWwQU05NjB5IF2= NXSwdVl5OjJ|M{[yOFY>
DMS273 NETBdYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVKz[pdMOC5yMT2xNFAh|ryP NETET5E1QCCq MnezUI9oKEeLNUC9MVcvQDBiTR?= NIHINmkzOjN|NkK0Oi=>
DMS114 MnH1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWG1ZWtmOC5yMT2xNFAh|ryP M3j2b|Q5KGh? MX3Mc4chT0l3ME2tPE4{QSCP NIm3PXgzOjN|NkK0Oi=>
LOXIMVI MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3:4XlAvODFvMUCwJO69VQ>? NGjvb2Y1QCCq NETMSFRNd2diR1m1NF0uQC54NjDN M{\lOVIzOzN4MkS2
OVCAR3 Mnq3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2D2eFAvODFvMUCwJO69VQ>? M3TVfFQ5KGh? M{HMVWxw\yCJSUWwQU05NjF5IF2= M3Gz[|IzOzN4MkS2
OVCAR4 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWmwMlAyNTFyMDFOwG0> MUO0PEBp M1\kWWxw\yCJSUWwQU05NjV6IF2= NF\ONnAzOjN|NkK0Oi=>
OVCAR5 Mn2xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7H[Iw4OC5yMT2xNFAh|ryP M{ntblQ5KGh? MoTZUI9oKEeLNUC9MVcvPTdiTR?= MkX5NlI{OzZ{NE[=
OVCAR8 MlrmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3i0e|AvODFvMUCwJO69VQ>? M4K3UVQ5KGh? NGXQXoZNd2diR1m1NF0uPy56NDDN NV\ZbHBNOjJ|M{[yOFY>
SKOV3 NHPQVYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPRNE4xOS1zMECg{txO MljrOFghcA>? MnLlUI9oKEeLNUC9MVgvPDFiTR?= NWjYWGd2OjJ|M{[yOFY>
RXF631L MojxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2m2SFAvODFvMUCwJO69VQ>? MWW0PEBp MXXMc4chT0l3ME2tPE4zOSCP NWfOO242OjJ|M{[yOFY>
ACHN NUHCR|dnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnWfWFLOC5yMT2xNFAh|ryP NWXIWpVMPDhiaB?= Mkn2UI9oKEeLNUC9MVcvQTViTR?= NGPBT2QzOjN|NkK0Oi=>
St-4 Mo\OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTEfFM{OC5yMT2xNFAh|ryP NUDCTZVKPDhiaB?= NG\Ge4pNd2diR1m1NF0uPy52NzDN Mo[4NlI{OzZ{NE[=
MKN1 NXTuZlB1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\MNE4xOS1zMECg{txO NGjGVIM1QCCq NF3odVFNd2diR1m1NF0uQC52MTDN MoLINlI{OzZ{NE[=
MKN7 NWHXT|NqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEGwS3MxNjBzLUGwNEDPxE1? NHe2T|U1QCCq MVHMc4chT0l3ME2tO{43QCCP NFf3dHUzOjN|NkK0Oi=>
MKN28 M4LzR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPwcnM{OC5yMT2xNFAh|ryP Ml\SOFghcA>? M{XzXWxw\yCJSUWwQU04NjB5IF2= NVLQ[mpnOjJ|M{[yOFY>
MKN45 NYPkWlJ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{D5bFAvODFvMUCwJO69VQ>? NWr5TpRqPDhiaB?= MXnMc4chT0l3ME2tPE4{PCCP NUfYSZhuOjJ|M{[yOFY>
MKN74 M3f5UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnBWpcxNjBzLUGwNEDPxE1? M3vzWFQ5KGh? NInGdJhNd2diR1m1NF0uPy52MjDN NXLLdHM5OjJ|M{[yOFY>
DU145 Mnj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDWT2ExNjBzLUGwNEDPxE1? NXLHToZrPDhiaB?= MWPMc4chT0l3ME2tPE4yPiCP NF3oWXUzOjN|NkK0Oi=>
PC3 M{DjeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEP0OJIxNjBzLUGwNEDPxE1? MlTIOFghcA>? MluxUI9oKEeLNUC9MVgvPjZiTR?= NHT0RYUzOjN|NkK0Oi=>
Trypanosoma brucei brucei MmrGSpVv[3Srb36gRZN{[Xl? MVyyNFAhdk1? NVPidppJOTJiaB?= MnPrSG1UVw>? NXS5b4xMTGWlcnXhd4UhcW5icHjvd5Bpd3SrZInsJIlvd3OrdH;sJJBpd3OyaHH0[UBt\X[nbB?= NUXRPFJsOjR6MEW5OFY>
Trypanosoma brucei brucei M1znUmZ2dmO2aX;uJGF{e2G7 MmDKNVghcA>? MX3EUXNQ Mn7aTY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? M4X4OlI1QDB3OUS2
Trypanosoma brucei brucei M3jhNGZ2dmO2aX;uJGF{e2G7 M3;1N|IxOCCwTR?= MlLSNVIhcA>? MmjQSG1UVw>? MlfGSYZn\WO2IH;uJJNxcGmwZ3;tfYxmcW5ibHX2[Yw> Ml7wNlQ5ODV7NE[=
Trypanosoma brucei brucei M{TON2Z2dmO2aX;uJGF{e2G7 NFzF[GYzODBibl2= M1zlTlEzKGh? MkS4SG1UVw>? NF21NodG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> NG\CWZYzPDhyNUm0Oi=>
UM-UC-3 MnzrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDVR45iUUN3ME2zNVUheE1? NVXjVmZsW0GQR1XS
SBC-1 MlXtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTd2MjDwUS=> M3q5WHNCVkeHUh?=
MKN1 NGTUPJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGf1Z21KSzVyPUKuPEBvVQ>? NF2yeWRUSU6JRWK=
NCI-H720 MoDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3PBNmlEPTB;Mz61O{BvVQ>? MUTTRW5ITVJ?
BFTC-909 NEHIbnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjqVlZpUUN3ME2zMlcyKG6P M2jYWnNCVkeHUh?=
BPH-1 NX\rb2x{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfxTWM2OD12Lke2JI5O MYPTRW5ITVJ?
PC-3 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fteGlEPTB;NT6wPUBvVQ>? MYTTRW5ITVJ?
AN3-CA MojqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTVwNU[gcm0> NH:3[2dUSU6JRWK=
HN MnfRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nGWGlEPTB;NT65OkBvVQ>? M171UHNCVkeHUh?=
HCC2218 MlHvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmriTWM2OD14Lk[xJI5O MVnTRW5ITVJ?
KP-4 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnle45MUUN3ME23JI5O MnXmV2FPT0WU
LU-139 M4nCc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLQTWM2OD15Lke3JI5O NWnR[IZvW0GQR1XS
ETK-1 MnvYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjIZXNKSzVyPUeuPFghdk1? MoTIV2FPT0WU
Ramos-2G6-4C10 M3\iS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXfINVhJUUN3ME24MlQ6KG6P MlzaV2FPT0WU
MHH-PREB-1 NF3JSHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHJ[o1KSzVyPUmuNVIhdk1? NETaXohUSU6JRWK=
DU-4475 NWnuTVluT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDRcZZ6UUN3ME25MlQ1KG6P M{XsSnNCVkeHUh?=
NCI-H1666 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXLZRmc2UUN3ME25MlcyKG6P MlzIV2FPT0WU
CAMA-1 NUTIU2I{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2n2XGlEPTB;OT64JI5O MWXTRW5ITVJ?
TYK-nu MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjnVlg1UUN3ME25Mlk1KG6P NIrWdIlUSU6JRWK=
MFE-280 NXnDellPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmjtTWM2OD17Lkm5JI5O MlHhV2FPT0WU
A549 NFPFWIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjJTWM2OD1zMD6xOEBvVQ>? M331W3NCVkeHUh?=
769-P NUHqdHRjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHiTWM2OD1zMD60OEBvVQ>? MV\TRW5ITVJ?
L-363 MlzrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml72TWM2OD1zMD62PUBvVQ>? NIq0W|dUSU6JRWK=
ES8 NILYXnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrmTWM2OD1zMD65JI5O MXfTRW5ITVJ?
PA-1 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTFzLkiyJI5O MWHTRW5ITVJ?
Mewo NUXBOoRwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLNRlMyUUN3ME2xNU46QSCwTR?= MkO4V2FPT0WU
HSC-3 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnT0TWM2OD1zMj6yNUBvVQ>? NFnDSIFUSU6JRWK=
H4 NFztTXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFf2Vo9KSzVyPUGyMlY4KG6P MYHTRW5ITVJ?
BB65-RCC M1PpO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVGxe2tRUUN3ME2xNk44OiCwTR?= MXjTRW5ITVJ?
NCI-H1793 NW[5b2t3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkjHTWM2OD1zMj64NkBvVQ>? M4XTOXNCVkeHUh?=
KARPAS-45 NYDJOo0{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4j0TmlEPTB;MUOuOVEhdk1? Ml[0V2FPT0WU
GCT NEjNfZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\uTWM2OD1zMz62PEBvVQ>? NYHjV5JtW0GQR1XS
EoL-1 NEXIOlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXeyWVJ6UUN3ME2xN{46OyCwTR?= NHX2PHNUSU6JRWK=
LB2241-RCC M13IO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2X2bmlEPTB;MUSuNFEhdk1? MUXTRW5ITVJ?
ES5 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF7MVWVKSzVyPUG0Mlc1KG6P M2TF[nNCVkeHUh?=
LOXIMVI M1\idGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGrrSopKSzVyPUG0Mlk6KG6P MlWyV2FPT0WU
COR-L105 M3frXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XxcGlEPTB;MUWuNFQhdk1? NXTNflRFW0GQR1XS
P12-ICHIKAWA MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTF3LkGgcm0> MW\TRW5ITVJ?
CHL-1 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{PTSWlEPTB;MUWuOFUhdk1? MWTTRW5ITVJ?
VMRC-RCZ NWS1Tml3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV3JR|UxRTF3Lk[zJI5O Ml7DV2FPT0WU
HH M3zxOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfUZW5jUUN3ME2xOU44KG6P NWHCSmNqW0GQR1XS
NUGC-3 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXtTWM2OD1zNj6zOEBvVQ>? MVLTRW5ITVJ?
EGI-1 MoHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTF4LkSzJI5O NXj2eVRuW0GQR1XS
OS-RC-2 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnvBTWM2OD1zNj60O{BvVQ>? M3zsWHNCVkeHUh?=
MOLT-16 MnPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTF5LkG1JI5O MljKV2FPT0WU
NCI-H209 NUHEd3BDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHRXVhKSzVyPUG3MlI6KG6P M2HlRnNCVkeHUh?=
697 NH[1eo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1XOWmlEPTB;MUeuOFMhdk1? Ml71V2FPT0WU
D-56MG MoDuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTF5Lk[5JI5O NVHCVWlZW0GQR1XS
VA-ES-BJ M{PWSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTF5LkizJI5O NXL3R49pW0GQR1XS
EW-16 Mli0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrXSnFPUUN3ME2xPE4xPCCwTR?= NXHxUGxJW0GQR1XS
HGC-27 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TkVGlEPTB;MUiuNFYhdk1? MX3TRW5ITVJ?
ES7 NGHPenVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\BZoF{UUN3ME2xPE4xQSCwTR?= M2nib3NCVkeHUh?=
HuH-7 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTF6LkSgcm0> M4X5OXNCVkeHUh?=
BCPAP M3nhdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGi0XoJKSzVyPUG4MlY2KG6P MXLTRW5ITVJ?
SW1710 MoLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NES3cIxKSzVyPUG4MlczKG6P MkLOV2FPT0WU
IST-MEL1 MmLuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\UR2lEPTB;MUiuO|chdk1? NX\ENVJEW0GQR1XS
SF295 Mm\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofkTWM2OD1zOD65N{BvVQ>? NXO1UIpRW0GQR1XS
RPMI-7951 MkfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV7xN3NyUUN3ME2xPU4zQCCwTR?= M4HqbHNCVkeHUh?=
SF126 M4r4S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fv[2lEPTB;MUmuOFEhdk1? NVHDeFI2W0GQR1XS
GAMG NI\FS3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjYWXI2UUN3ME2xPU41QCCwTR?= NFrzZ2FUSU6JRWK=
KNS-81-FD M3HFdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTF7LkW0JI5O MkL3V2FPT0WU
RT-112 NEjZfHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLRTWM2OD1zOT62OkBvVQ>? NELFRnNUSU6JRWK=
DEL Mn\NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjOS5lKSzVyPUKwMlQ6KG6P MXjTRW5ITVJ?
CGTH-W-1 M1qwXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTJyLk[zJI5O NFm5ZoNUSU6JRWK=
HOS MmnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTJzLkC2JI5O NUTCc|c2W0GQR1XS
ES4 M13nTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVLaToZ1UUN3ME2yNU4xQCCwTR?= M3zsPHNCVkeHUh?=
RXF393 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLPTWM2OD1{MT60OUBvVQ>? MWXTRW5ITVJ?
NCI-H2030 NXOyfoE5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWH4TYR{UUN3ME2yNU42OiCwTR?= MnLiV2FPT0WU
YH-13 MoS5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\YNmRuUUN3ME2yNU45QCCwTR?= NULLU2N4W0GQR1XS
HT-1080 Ml\5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3oZZVKSzVyPUKxMlk{KG6P NUDhZXV3W0GQR1XS
NCI-SNU-1 M2nFSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTJzLkm1JI5O NIO5XXRUSU6JRWK=
G-402 MmLyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjxTWM2OD1{Mj6xOkBvVQ>? NInSfmdUSU6JRWK=
786-0 MkO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7HV2ZKSzVyPUKyMlI6KG6P NFTWcJVUSU6JRWK=
ME-180 NWPQRZRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4nmbGlEPTB;MkKuOFMhdk1? MWfTRW5ITVJ?
NB69 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPkS2FKSzVyPUKyMlU{KG6P NUHET29WW0GQR1XS
J-RT3-T3-5 NFXGUHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2exdGlEPTB;MkKuPVYhdk1? MXLTRW5ITVJ?
TGBC1TKB NWL1[VVYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInrT|FKSzVyPUKzMlA2KG6P MW\TRW5ITVJ?
SW780 NX7YbW9lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTJ|LkGzJI5O NYrtdlJHW0GQR1XS
MG-63 MojaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnpWJNKSzVyPUKzMlQ2KG6P M1j2[nNCVkeHUh?=
BV-173 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;6THJpUUN3ME2yN{45PyCwTR?= M1vpeHNCVkeHUh?=
CAL-51 Mo\xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jkdmlEPTB;MkOuPFkhdk1? NGPVW3NUSU6JRWK=
A375 MlXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3BTWM2OD1{Mz65N{BvVQ>? NXzpOHVyW0GQR1XS
MEL-HO M{nwOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjod3NKSzVyPUK0MlA1KG6P NXvCS2pMW0GQR1XS
EFO-27 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3LTWM2OD1{ND6zN{BvVQ>? NYrrSFk1W0GQR1XS
Hs-578-T MnnkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTJ2LkW4JI5O NHfhXphUSU6JRWK=
NBsusSR NIrPV3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTJ2Lk[gcm0> MYrTRW5ITVJ?
CTB-1 Mor4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUXIZ5dDUUN3ME2yOE43PyCwTR?= NUmxXYNSW0GQR1XS
FTC-133 M1L4Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfWfnZKSzVyPUK1MlEhdk1? NULkdJNDW0GQR1XS
MOLT-4 M2f2XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVu4[FBlUUN3ME2yOU4yOiCwTR?= M{DOcHNCVkeHUh?=
HO-1-N-1 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTJ3LkG1JI5O MmrjV2FPT0WU
ES3 NX3LOWFoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXlTWM2OD1{NT6yNkBvVQ>? M{XMV3NCVkeHUh?=
TI-73 Mn7vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPQ[3pOUUN3ME2yOU4zQCCwTR?= M1SydXNCVkeHUh?=
MPP-89 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFH2d2tKSzVyPUK1MlMzKG6P NXroRVZxW0GQR1XS
KYSE-150 NFHEeWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFTUO|VKSzVyPUK1Mlg6KG6P NHTFN3NUSU6JRWK=
LXF-289 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnzuTWM2OD1{Nj6wOEBvVQ>? NIThVJpUSU6JRWK=
SK-LU-1 MoDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTJ4LkG3JI5O M4P3[XNCVkeHUh?=
HOP-92 NH3Fbo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVLJR|UxRTJ4LkS4JI5O MoTHV2FPT0WU
HuO9 M1SzTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTJ4Lke2JI5O MnX4V2FPT0WU
SW962 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkGzTWM2OD1{Nj63OkBvVQ>? NEXHepFUSU6JRWK=
RS4-11 M1fXUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFjoR49KSzVyPUK2MlkyKG6P Ml\ZV2FPT0WU
NCI-H292 M2Ljbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TDc2lEPTB;Mkegcm0> NU\3eJFCW0GQR1XS
DB NU\WXJBnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTJ5LkO2JI5O MYTTRW5ITVJ?
SW1088 NVLmeZdPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVfJR|UxRTJ6LkK5JI5O NF\rcmpUSU6JRWK=
A204 NEPYe4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzWU4lqUUN3ME2yPE41PyCwTR?= MYjTRW5ITVJ?
A3-KAW M3\JZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXu[lZ{UUN3ME2yPE43PCCwTR?= NY\qW5RNW0GQR1XS
MV-4-11 NUjmc5JCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTJ6Lkegcm0> MVnTRW5ITVJ?
ES1 MnvMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2qxU2lEPTB;MkiuPFQhdk1? NVTjdYt1W0GQR1XS
ONS-76 Mm\hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPXTWM2OD1{OT6wOUBvVQ>? M2DM[nNCVkeHUh?=
D-263MG NF3DfHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rh[2lEPTB;MkmuN|Uhdk1? NXLXNZRPW0GQR1XS
U-2-OS MnvoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXtbm1KSzVyPUK5MlUhdk1? M1;3fXNCVkeHUh?=
T98G MkfDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\PdWFZUUN3ME2yPU45QCCwTR?= MYPTRW5ITVJ?
GI-ME-N NIXsW4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvD[ZB6UUN3ME2yPU46OSCwTR?= NGnIN|VUSU6JRWK=
BHT-101 MnHKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PXOGlEPTB;M{CuNFUhdk1? NXfkRWRpW0GQR1XS
NOS-1 NG\WOo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXLsNW5HUUN3ME2zNE4yOiCwTR?= MlOwV2FPT0WU
AsPC-1 MmGxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\Pb5dKSzVyPUOwMlIhdk1? M4DUWHNCVkeHUh?=
QIMR-WIL NFL4XG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvhU4RTUUN3ME2zNE43KG6P NX7vNnR4W0GQR1XS
JVM-3 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEP3SJVKSzVyPUOwMlg{KG6P NFfGPZFUSU6JRWK=
KU-19-19 NVjtW|FrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rlcGlEPTB;M{GuNVMhdk1? MnzWV2FPT0WU
OVCAR-8 MlfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTNzLkK2JI5O NHLyfIxUSU6JRWK=
BEN NWTkZlhLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT3dJhKSzVyPUOxMlY{KG6P MV\TRW5ITVJ?
BE-13 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnW2TWM2OD1|MT64NkBvVQ>? NFnpcHNUSU6JRWK=
EW-18 M{XPTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3Pd4ZQUUN3ME2zNU45PiCwTR?= MYjTRW5ITVJ?
ECC10 M3P0UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWGxRmtpUUN3ME2zNU46PSCwTR?= M4LSTHNCVkeHUh?=
CTV-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTN{LkiyJI5O MmjWV2FPT0WU
COLO-800 NGrNPHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTN{LkmyJI5O NXrjd4VuW0GQR1XS
A2058 M{\xTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTwT2JYUUN3ME2zN{4zPSCwTR?= M13F[3NCVkeHUh?=
VM-CUB-1 NF21TZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTN|LkSzJI5O NY[5fldkW0GQR1XS
Ca9-22 Mke1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG[5[GtKSzVyPUOzMlU2KG6P NXSyNFh1W0GQR1XS
COLO-684 NU\TR4k6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXVTWM2OD1|Mz61PEBvVQ>? NVfnOHh6W0GQR1XS
RPMI-8226 MnS4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTN|LkiyJI5O MULTRW5ITVJ?
SK-NEP-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX\JR|UxRTN2LkG1JI5O MoH4V2FPT0WU
Becker M{fvc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfsTWM2OD1|ND6yNUBvVQ>? NUnhfZllW0GQR1XS
NCI-H28 NWr1N|RXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nYRWlEPTB;M{SuOFQhdk1? M{TjPHNCVkeHUh?=
CAL-120 MmnKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3X3[GlEPTB;M{SuO|Ihdk1? NXLZfoRrW0GQR1XS
MDA-MB-157 NXTjXGtxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPZTWM2OD1|NT60NUBvVQ>? NXfYe5BsW0GQR1XS
OVCAR-5 NGHwNZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4\tU2lEPTB;M{WuOFchdk1? NFrtcoRUSU6JRWK=
LAMA-84 NGrE[WZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojzTWM2OD1|NT64O{BvVQ>? MX;TRW5ITVJ?
CAKI-1 NWrpdXBrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofQTWM2OD1|Nj60N{BvVQ>? M1[ycHNCVkeHUh?=
Daoy M4r2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTkXVFKSzVyPUO2Mlchdk1? NUS3bWFpW0GQR1XS
CAL-62 M1PqfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW\SNFRvUUN3ME2zOk45PiCwTR?= MoS5V2FPT0WU
8-MG-BA NWq0cohjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTN5LkK1JI5O NWn3T5prW0GQR1XS
8505C NYTiUY41T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{PFZmlEPTB;M{euOVEhdk1? Mln0V2FPT0WU
LNCaP-Clone-FGC MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmn2TWM2OD1|Nz61PUBvVQ>? MojxV2FPT0WU
CAL-39 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWPJR|UxRTN5Lkmgcm0> MmrRV2FPT0WU
MN-60 MkHqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTN5Lkm2JI5O NYXzTJJiW0GQR1XS
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CO-314 Ml7HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnH2TWM2OD1|OD63OEBvVQ>? MXrTRW5ITVJ?
LB1047-RCC MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nU[GlEPTB;M{iuPFEhdk1? NVXLcmViW0GQR1XS
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NCI-H1623 NH7CZ3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\WTXZlUUN3ME20O{44PiCwTR?= MULTRW5ITVJ?
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D-423MG NGnHVoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{jnZWlEPTB;NUKuNFghdk1? M3zNO3NCVkeHUh?=
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AM-38 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLk[ppKSzVyPU[5MlMyKG6P MnjXV2FPT0WU
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OAW-28 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml;6TWM2OD1{LkC2PVE6KM7:TR?= MnXCV2FPT0WU
C8166 NGHFN29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnm0TWM2OD1{Lk[zN|kzKM7:TR?= M3v4SnNCVkeHUh?=
COLO-678 NHO3bGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFi2[5JKSzVyPUKuPFM4PjhizszN M3HiWnNCVkeHUh?=
SK-N-DZ MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDsTWM2OD1{Lki2N|gyKM7:TR?= NUfnZm9zW0GQR1XS
NCI-H82 NELkWYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVy5UGpYUUN3ME2yMlkxOzZ7IN88US=> NHOzUY9USU6JRWK=
JVM-2 NFXwW45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfHN|BKSzVyPUOuNFMyQDhizszN M2OyenNCVkeHUh?=
SW1116 MmLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjxUIozUUN3ME2zMlA2PDFzIN88US=> Mli2V2FPT0WU
MDA-MB-453 MlfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWTJR|UxRTNwMUC0N|kh|ryP NFm0blNUSU6JRWK=
Calu-6 NETDXFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnR[IRKSzVyPUOuNVk6PyEQvF2= MnfKV2FPT0WU
SHP-77 NH3UXFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWjJR|UxRTNwNUK4JO69VQ>? MWXTRW5ITVJ?
Capan-2 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7oTWM2OD12LkOyOVgyKM7:TR?= MmrxV2FPT0WU
SW948 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nEZWlEPTB;ND63OFc4QSEQvF2= MnLDV2FPT0WU
HDLM-2 M{PETWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGD0WJlKSzVyPUWuNFc4OjVizszN NGDCWVlUSU6JRWK=
LAN-6 M{DLPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLkcZJWUUN3ME22MlIyPDl3IN88US=> NHfSZoxUSU6JRWK=
LU-135 NFnaeW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGO3bnBKSzVyPU[uOFMxPzdizszN NVPV[YQ3W0GQR1XS
T84 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYW2ZY91UUN3ME22Mlk5PjRizszN MonIV2FPT0WU
CAPAN-1 MnfrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF24WZdKSzVyPUeuOlIzOzNizszN NH6w[WxUSU6JRWK=
SW1417 NGK5c5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\je2lIUUN3ME23MlkyPzNzIN88US=> M3LkWXNCVkeHUh?=
BALL-1 M17Ib2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MknOTWM2OD16LkWwOFA6KM7:TR?= NF2yU2ZUSU6JRWK=
HT-29 NWe4enc3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIO1XZRKSzVyPUmuNFc2QTlizszN NWPUU3FNW0GQR1XS
C3A NIrMOXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrWXW5yUUN3ME25Mlg5Ozl2IN88US=> MYfTRW5ITVJ?
NCI-H1993 MlvHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEXX[XVKSzVyPUGwMlUxQDFizszN MnHFV2FPT0WU
SK-MEL-1 NHTNfnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPlfWF{UUN3ME2xNU43Ojh7IN88US=> MoHoV2FPT0WU
DU-145 NXrhbpFJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTF2LkWwOVIh|ryP MUfTRW5ITVJ?
KP-N-YN MoLSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnQe2ZRUUN3ME2xOE42OTB|IN88US=> MUfTRW5ITVJ?
CCRF-CEM M2D0bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYTv[os2UUN3ME2xOE44QDB7IN88US=> MoHzV2FPT0WU
ZR-75-30 M2HGSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTF4LkOzNFMh|ryP NFHzcmJUSU6JRWK=
A673 NHHjcGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTJyLkW1NFch|ryP M4Kxe3NCVkeHUh?=
K-562 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnS3TWM2OD1{OD60NVg{KM7:TR?= M2LJZnNCVkeHUh?=

... 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).

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Molecular Weight Calculator

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

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Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01717898 Terminated Castrate-resistant Prostate Cancer Charles Ryan|Novartis Pharmaceuticals|University of California San Francisco January 31 2013 Phase 1|Phase 2
NCT00620594 Completed Breast Cancer|Advanced Solid Tumors|Cowden Syndrome Novartis Pharmaceuticals|Novartis December 21 2006 Phase 1
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01658436 Completed Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis November 2012 Phase 2
NCT01628913 Terminated Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis October 2012 Phase 2
NCT01690871 Withdrawn Malignant PEComa (Perivascular Epithelioid Cell Tumors) Novartis Pharmaceuticals|Novartis September 2012 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

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

  • Answer:

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID