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 82 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.

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

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

     

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

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

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

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

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

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

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

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

     

     

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

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

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

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

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

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

     

     

     

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

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

     

     

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

  •  

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

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

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

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

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei M{TYNGFvfGmvaXPyc4Jq[WxiQYPzZZk> NGD5S2syQCCq MXHEUXNQ NITPfHNCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP M2n2VFI1QDB3OUS2
MCF7 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzqdJExNjBzLUGwNEDPxE1? NI\yTZU1QCCq NF60OGhFVVOR NH;Yd4xKSzVyPUCuO|Mh|ryP NWDUVZVKOjN6N{G5NFQ>
HCT116 NVH4TVI4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4nFSVAvODFvMUCwJO69VQ>? MljSOFghcA>? MWXEUXNQ M{jUfGlEPTB;MT6xOkDPxE1? NInjdXAzOzh5MUmwOC=>
U87MG M2LkPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjPOo5mOC5yMT2xNFAh|ryP NFXlbHE1QCCq MVfEUXNQ MUjJR|UxRTFwM{Kg{txO NFLPSGkzOzh5MUmwOC=>
HBC4 MmTOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;TNE4xOS1zMECg{txO NGX1SYQ1QCCq NVG1N2o1VG:pIFfJOVA:NThwNkGgUS=> NXPDOoRvOjJ|M{[yOFY>
BSY1 M2jGcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfTbGsxNjBzLUGwNEDPxE1? Mlf1OFghcA>? M4e5UWxw\yCJSUWwQU05NjR6IF2= NH7tPIozOjN|NkK0Oi=>
HBC5 MnfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXtWoYxNjBzLUGwNEDPxE1? MoTKOFghcA>? M1Xh[mxw\yCJSUWwQU04Njh5IF2= MWSyNlM{PjJ2Nh?=
MCF7 NUDaZ2hpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVPWUJU2OC5yMT2xNFAh|ryP M1zKOlQ5KGh? MYnMc4chT0l3ME2tPE4yPiCP M3XBNFIzOzN4MkS2
MDA-MB-231 MomwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVuwMlAyNTFyMDFOwG0> M2r0TlQ5KGh? MVPMc4chT0l3ME2tPE4xQSCP MnXNNlI{OzZ{NE[=
U251 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmHmNE4xOS1zMECg{txO NVjXPHRoPDhiaB?= MomwUI9oKEeLNUC9MVcvPjZiTR?= NUS4U5VVOjJ|M{[yOFY>
SF268 NFjhN|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXP5cmJJOC5yMT2xNFAh|ryP MUi0PEBp MYfMc4chT0l3ME2tO{46OiCP M3LaUlIzOzN4MkS2
SF295 MnfBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXNNE4xOS1zMECg{txO MXO0PEBp NGP4[3hNd2diR1m1NF0uQC5|MTDN NWPWXZY4OjJ|M{[yOFY>
SF539 MkPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrVNE4xOS1zMECg{txO MluyOFghcA>? M4OxXGxw\yCJSUWwQU05NjV7IF2= M4\4[|IzOzN4MkS2
SNB75 NGnHfopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfqNE4xOS1zMECg{txO NEX3b2s1QCCq NHTaOW9Nd2diR1m1NF0uQC53ODDN MmK3NlI{OzZ{NE[=
SNB78 M37JSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXOwMlAyNTFyMDFOwG0> MonDOFghcA>? MWLMc4chT0l3ME2tPE43PSCP MorYNlI{OzZ{NE[=
HCC2998 NWH2NpV3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33vN|AvODFvMUCwJO69VQ>? NWPNdIxDPDhiaB?= MYPMc4chT0l3ME2tPE4xPSCP NVL0[o1GOjJ|M{[yOFY>
KM12 NHnqN2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGD1eXAxNjBzLUGwNEDPxE1? M3LWVFQ5KGh? MU\Mc4chT0l3ME2tO{42PCCP NWXHcpRVOjJ|M{[yOFY>
HT-29 NYHZfGNjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmP6NE4xOS1zMECg{txO NX3wU4FkPDhiaB?= MXvMc4chT0l3ME2tO{44PSCP MmnoNlI{OzZ{NE[=
HCT15 NGLXVIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnYNE4xOS1zMECg{txO NH[5eVI1QCCq MXvMc4chT0l3ME2tPE4xOyCP MlziNlI{OzZ{NE[=
HCT116 NFTrO2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFrhTmsxNjBzLUGwNEDPxE1? MY[0PEBp MnuwUI9oKEeLNUC9MVcvPjFiTR?= MUGyNlM{PjJ2Nh?=
NCI-H23 Mkj1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDBNE4xOS1zMECg{txO NVLEOZk1PDhiaB?= NWP5SY8{VG:pIFfJOVA:NTdwNkSgUS=> MYWyNlM{PjJ2Nh?=
NCI-H226 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfjWVQxNjBzLUGwNEDPxE1? MmLSOFghcA>? MnHNUI9oKEeLNUC9MVgvPDRiTR?= M2PNc|IzOzN4MkS2
NCI-H522 M33ES2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rhOFAvODFvMUCwJO69VQ>? MYO0PEBp NUHtXZl2VG:pIFfJOVA:NThwNEWgUS=> NH\RU20zOjN|NkK0Oi=>
NCI-H438 NGqzTmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUGwMlAyNTFyMDFOwG0> NGD2PWo1QCCq NWjwdol4VG:pIFfJOVA:NThwMUGgUS=> NWTSXoxpOjJ|M{[yOFY>
A549 MkezS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXBR|V[OC5yMT2xNFAh|ryP M{jKUlQ5KGh? M37Ifmxw\yCJSUWwQU05NjB5IF2= M{XkfVIzOzN4MkS2
DMS273 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYq1[ItPOC5yMT2xNFAh|ryP NHvTTXQ1QCCq M4O2Nmxw\yCJSUWwQU04NjhyIF2= NVLBb|JHOjJ|M{[yOFY>
DMS114 M1\jNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUKwMlAyNTFyMDFOwG0> MnLHOFghcA>? MUPMc4chT0l3ME2tPE4{QSCP NITre5IzOjN|NkK0Oi=>
LOXIMVI M1HYSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1LiTVAvODFvMUCwJO69VQ>? M4HidVQ5KGh? M{jB[2xw\yCJSUWwQU05NjZ4IF2= NYW4c3k1OjJ|M{[yOFY>
OVCAR3 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY[wMlAyNTFyMDFOwG0> MYe0PEBp MoC2UI9oKEeLNUC9MVgvOTdiTR?= NX:ybG5rOjJ|M{[yOFY>
OVCAR4 NVTYTYdxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nxR|AvODFvMUCwJO69VQ>? NUThcGE4PDhiaB?= M1[wc2xw\yCJSUWwQU05NjV6IF2= NHHD[WEzOjN|NkK0Oi=>
OVCAR5 MlXrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvocWMxNjBzLUGwNEDPxE1? MnLkOFghcA>? MorLUI9oKEeLNUC9MVcvPTdiTR?= NGDDTVEzOjN|NkK0Oi=>
OVCAR8 M3vTSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXmwMlAyNTFyMDFOwG0> MV60PEBp NUi0bXFnVG:pIFfJOVA:NTdwOESgUS=> MoDaNlI{OzZ{NE[=
SKOV3 Ml7aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7CNE4xOS1zMECg{txO MVW0PEBp NVPxd25uVG:pIFfJOVA:NThwNEGgUS=> M3nseFIzOzN4MkS2
RXF631L MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NU\Z[JlOOC5yMT2xNFAh|ryP M4TBNVQ5KGh? NF\t[2ZNd2diR1m1NF0uQC5{MTDN M4\SO|IzOzN4MkS2
ACHN MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYO5b29qOC5yMT2xNFAh|ryP MV20PEBp MVXMc4chT0l3ME2tO{46PSCP NGXy[3QzOjN|NkK0Oi=>
St-4 M{TJZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn;ENE4xOS1zMECg{txO NFfIPZg1QCCq MVrMc4chT0l3ME2tO{41PyCP M{DZTVIzOzN4MkS2
MKN1 NYDsOmRmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHWfoJlOC5yMT2xNFAh|ryP M4XUclQ5KGh? NWjJfJpjVG:pIFfJOVA:NThwNEGgUS=> MV:yNlM{PjJ2Nh?=
MKN7 M1\TUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYWwMlAyNTFyMDFOwG0> NYrmUVhSPDhiaB?= NIj3fGpNd2diR1m1NF0uPy54ODDN M323TlIzOzN4MkS2
MKN28 MlTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfT[VcxNjBzLUGwNEDPxE1? M361OVQ5KGh? MYLMc4chT0l3ME2tO{4xPyCP MVSyNlM{PjJ2Nh?=
MKN45 NHr2NIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPXSncxNjBzLUGwNEDPxE1? MlXKOFghcA>? MnPuUI9oKEeLNUC9MVgvOzRiTR?= M33DflIzOzN4MkS2
MKN74 MmPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkHLNE4xOS1zMECg{txO MojKOFghcA>? M2e5NGxw\yCJSUWwQU04NjR{IF2= NFHtbHkzOjN|NkK0Oi=>
DU145 NF3yTZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV:wMlAyNTFyMDFOwG0> NEnpT|Y1QCCq NYC5UJRsVG:pIFfJOVA:NThwMU[gUS=> MXOyNlM{PjJ2Nh?=
PC3 Mnv4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUewMlAyNTFyMDFOwG0> M3HQTVQ5KGh? M2PuS2xw\yCJSUWwQU05NjZ4IF2= NV7JUI5{OjJ|M{[yOFY>
Trypanosoma brucei brucei M4XobmZ2dmO2aX;uJGF{e2G7 M4[1TVIxOCCwTR?= MWCxNkBp MXjEUXNQ MUnE[YNz\WG|ZTDpckBxcG:|cHjveIllgWxiaX7vd4l1d2xicHjvd5Bp[XSnIHzleoVt MWCyOFgxPTl2Nh?=
Trypanosoma brucei brucei MX3GeY5kfGmxbjDBd5NigQ>? NHjLXowyQCCq M4GzVGROW09? NWXXb|ZTUW6qaXLpeIlwdiCxZjDy[YNmeHSxcj3t[YRq[XSnZDDlcoRw[3m2b4Ppd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjD0doFve2[ncoLpckB2eHSja3W= M4\SVFI1QDB3OUS2
Trypanosoma brucei brucei MUTGeY5kfGmxbjDBd5NigQ>? NEW5eoczODBibl2= NUTZbmxFOTJiaB?= M2LzRmROW09? NXXwcZBTTW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? MVqyOFgxPTl2Nh?=
Trypanosoma brucei brucei M{n5XWZ2dmO2aX;uJGF{e2G7 MXiyNFAhdk1? Mlf5NVIhcA>? M33QUWROW09? NHLDbGNG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> M2\WdlI1QDB3OUS2
UM-UC-3 NVnld5liT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmKwTWM2OD1|MUWgdG0> MlnuV2FPT0WU
SBC-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXYV4RPUUN3ME23OFIheE1? NUjNc21yW0GQR1XS
MKN1 NGrZOYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjYUVZbUUN3ME2yMlghdk1? MmDtV2FPT0WU
NCI-H720 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWLJR|UxRTNwNUegcm0> MmfUV2FPT0WU
BFTC-909 NInMO3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2\WTmlEPTB;Mz63NUBvVQ>? NHvGcZhUSU6JRWK=
BPH-1 M2nD[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXf6fmFnUUN3ME20Mlc3KG6P NFjtVFJUSU6JRWK=
PC-3 M2TMWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnCWXdKSzVyPUWuNFkhdk1? MUHTRW5ITVJ?
AN3-CA M2G2SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTVwNU[gcm0> NEPYSHVUSU6JRWK=
HN MofqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4SwfWlEPTB;NT65OkBvVQ>? MUjTRW5ITVJ?
HCC2218 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnleo5KSzVyPU[uOlEhdk1? M{Dhd3NCVkeHUh?=
KP-4 NXPTeXpmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVvafYtwUUN3ME23JI5O NXnkXpNvW0GQR1XS
LU-139 M1\pPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGi2RW9KSzVyPUeuO|chdk1? MkXTV2FPT0WU
ETK-1 NHLGTZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTdwOEigcm0> NVzOb2xWW0GQR1XS
Ramos-2G6-4C10 Mn7BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVizU297UUN3ME24MlQ6KG6P M3f1T3NCVkeHUh?=
MHH-PREB-1 M3PqS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfwTWM2OD17LkGyJI5O NGGxRmxUSU6JRWK=
DU-4475 M3\tV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\QTWM2OD17LkS0JI5O NGPzZXZUSU6JRWK=
NCI-H1666 NHT3V4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF36O2ZKSzVyPUmuO|Ehdk1? M1fUVXNCVkeHUh?=
CAMA-1 MmfPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{X0S2lEPTB;OT64JI5O NU\GOGtMW0GQR1XS
TYK-nu MoTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTlwOUSgcm0> MV7TRW5ITVJ?
MFE-280 NFzjNHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2e1OGlEPTB;OT65PUBvVQ>? NWL4TmV[W0GQR1XS
A549 NEjLfpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{njXGlEPTB;MUCuNVQhdk1? NYLvVXY1W0GQR1XS
769-P M1XE[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfoSHFPUUN3ME2xNE41PCCwTR?= NHzBfmNUSU6JRWK=
L-363 NWTjXopoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2X6VWlEPTB;MUCuOlkhdk1? MYXTRW5ITVJ?
ES8 M2q0O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnK0TWM2OD1zMD65JI5O MlnwV2FPT0WU
PA-1 M{Ht[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnRS4hKSzVyPUGxMlgzKG6P M2H6R3NCVkeHUh?=
Mewo M4fHV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\3OXVwUUN3ME2xNU46QSCwTR?= NEDjenRUSU6JRWK=
HSC-3 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DPfWlEPTB;MUKuNlEhdk1? NIi2NJZUSU6JRWK=
H4 M4TSZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDZfJJKSzVyPUGyMlY4KG6P NF\vbGNUSU6JRWK=
BB65-RCC MkjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHueoJKSzVyPUGyMlczKG6P MX\TRW5ITVJ?
NCI-H1793 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2riWmlEPTB;MUKuPFIhdk1? MojaV2FPT0WU
KARPAS-45 M1vERmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXCeYxKSzVyPUGzMlUyKG6P MWXTRW5ITVJ?
GCT MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2fw[mlEPTB;MUOuOlghdk1? M4HqSHNCVkeHUh?=
EoL-1 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTF|LkmzJI5O NGDJcG9USU6JRWK=
LB2241-RCC M4P2VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYP1cYhoUUN3ME2xOE4xOSCwTR?= MXXTRW5ITVJ?
ES5 MnjuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjFcWlKSzVyPUG0Mlc1KG6P MXvTRW5ITVJ?
LOXIMVI NHS4XIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDFdYlKSzVyPUG0Mlk6KG6P NFTkemdUSU6JRWK=
COR-L105 NYXVWIdQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjtSZJpUUN3ME2xOU4xPCCwTR?= MoCxV2FPT0WU
P12-ICHIKAWA NGq3[3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGf1dVhKSzVyPUG1MlEhdk1? MmPCV2FPT0WU
CHL-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2rFfmlEPTB;MUWuOFUhdk1? M{HRZXNCVkeHUh?=
VMRC-RCZ Mn\xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWnJR|UxRTF3Lk[zJI5O M4naO3NCVkeHUh?=
HH NWju[FA3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfHVGJRUUN3ME2xOU44KG6P MWPTRW5ITVJ?
NUGC-3 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4OzRWlEPTB;MU[uN|Qhdk1? MYHTRW5ITVJ?
EGI-1 NGHKbHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LlWWlEPTB;MU[uOFMhdk1? NFH6O5lUSU6JRWK=
OS-RC-2 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7MTWM2OD1zNj60O{BvVQ>? NVrsOnVnW0GQR1XS
MOLT-16 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnRTWM2OD1zNz6xOUBvVQ>? MUHTRW5ITVJ?
NCI-H209 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjoTWM2OD1zNz6yPUBvVQ>? NFjzRoZUSU6JRWK=
697 NWX0d|JtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rGXWlEPTB;MUeuOFMhdk1? M2i5eXNCVkeHUh?=
D-56MG NX;PWGJ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mme5TWM2OD1zNz62PUBvVQ>? MmDpV2FPT0WU
VA-ES-BJ NIjnWmFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfwSWlwUUN3ME2xO{45OyCwTR?= MmXJV2FPT0WU
EW-16 MofDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2jKTGlEPTB;MUiuNFQhdk1? MlrBV2FPT0WU
HGC-27 NXPOb|dET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\4fGlEPTB;MUiuNFYhdk1? MULTRW5ITVJ?
ES7 MmPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rlW2lEPTB;MUiuNFkhdk1? NFzvS3hUSU6JRWK=
HuH-7 M4G2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTF6LkSgcm0> NFXQPXJUSU6JRWK=
BCPAP M2X6[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1LrWWlEPTB;MUiuOlUhdk1? NFjjfHdUSU6JRWK=
SW1710 NXjDNoN2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fBPWlEPTB;MUiuO|Ihdk1? MXfTRW5ITVJ?
IST-MEL1 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHf5dWNKSzVyPUG4Mlc4KG6P M33H[nNCVkeHUh?=
SF295 NUfVZZNpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTF6LkmzJI5O M{DEcnNCVkeHUh?=
RPMI-7951 M3zLbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLWO3hKSzVyPUG5MlI5KG6P NITtfVdUSU6JRWK=
SF126 NX\CcI1lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\yfGlEPTB;MUmuOFEhdk1? NWDJcYR7W0GQR1XS
GAMG NIrxU|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfFTWM2OD1zOT60PEBvVQ>? MVPTRW5ITVJ?
KNS-81-FD MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXqTWM2OD1zOT61OEBvVQ>? MVXTRW5ITVJ?
RT-112 NWj3[oJPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljaTWM2OD1zOT62OkBvVQ>? MojYV2FPT0WU
DEL M{i3TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mm\iTWM2OD1{MD60PUBvVQ>? MkTNV2FPT0WU
CGTH-W-1 M{[0c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoDFTWM2OD1{MD62N{BvVQ>? MmD4V2FPT0WU
HOS NFPSTmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTJzLkC2JI5O MVrTRW5ITVJ?
ES4 MoLpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M33icmlEPTB;MkGuNFghdk1? Mn:0V2FPT0WU
RXF393 NGLpfo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;6XVJrUUN3ME2yNU41PSCwTR?= M1PBfnNCVkeHUh?=
NCI-H2030 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFfuXmNKSzVyPUKxMlUzKG6P NGfJOXBUSU6JRWK=
YH-13 NIfWRmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXvJR|UxRTJzLki4JI5O NYHkbFhRW0GQR1XS
HT-1080 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofKTWM2OD1{MT65N{BvVQ>? NXXNU3hmW0GQR1XS
NCI-SNU-1 M2PSbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHITWM2OD1{MT65OUBvVQ>? M{XmdXNCVkeHUh?=
G-402 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHjQ[nJKSzVyPUKyMlE3KG6P MYDTRW5ITVJ?
786-0 NIPQfoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkT2TWM2OD1{Mj6yPUBvVQ>? M3;BVXNCVkeHUh?=
ME-180 MnvCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXW4[ZUxUUN3ME2yNk41OyCwTR?= M3LNcXNCVkeHUh?=
NB69 MknHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTJ{LkWzJI5O MmD3V2FPT0WU
J-RT3-T3-5 Ml\IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTJ{Lkm2JI5O Ml3MV2FPT0WU
TGBC1TKB MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTJ|LkC1JI5O Mn;ZV2FPT0WU
SW780 NXHXN2U3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHG3bmRKSzVyPUKzMlE{KG6P MYnTRW5ITVJ?
MG-63 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIntRZFKSzVyPUKzMlQ2KG6P MXzTRW5ITVJ?
BV-173 NX3tOFh2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm[wTWM2OD1{Mz64O{BvVQ>? MUHTRW5ITVJ?
CAL-51 NWPzc|U3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLOTWM2OD1{Mz64PUBvVQ>? NFG5bFZUSU6JRWK=
A375 NUf5O5FPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnoTWM2OD1{Mz65N{BvVQ>? NWrYSnp1W0GQR1XS
MEL-HO MmTYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLzTWM2OD1{ND6wOEBvVQ>? MkDCV2FPT0WU
EFO-27 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnXiTWM2OD1{ND6zN{BvVQ>? MV;TRW5ITVJ?
Hs-578-T MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPHd5JZUUN3ME2yOE42QCCwTR?= NHLhSoZUSU6JRWK=
NBsusSR MlTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjYTpBKSzVyPUK0MlYhdk1? NHiwclBUSU6JRWK=
CTB-1 NVfV[JhVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmf5TWM2OD1{ND62O{BvVQ>? NUHafm5GW0GQR1XS
FTC-133 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnTPHl6UUN3ME2yOU4yKG6P MmjPV2FPT0WU
MOLT-4 NXP2[WpXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHHZfldKSzVyPUK1MlEzKG6P NEfmUHhUSU6JRWK=
HO-1-N-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHn3RpVKSzVyPUK1MlE2KG6P Mmr3V2FPT0WU
ES3 M{PhN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUnN[5VFUUN3ME2yOU4zOiCwTR?= NHXPbpdUSU6JRWK=
TI-73 NETLXpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnNc3VKSzVyPUK1MlI5KG6P MU\TRW5ITVJ?
MPP-89 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoX2TWM2OD1{NT6zNkBvVQ>? MULTRW5ITVJ?
KYSE-150 Mn3oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXMcXdKSzVyPUK1Mlg6KG6P NFj0flVUSU6JRWK=
LXF-289 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2W3NWlEPTB;Mk[uNFQhdk1? NXm3[ohmW0GQR1XS
SK-LU-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjJR|UxRTJ4LkG3JI5O NXu4PJY{W0GQR1XS
HOP-92 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DNO2lEPTB;Mk[uOFghdk1? MlHjV2FPT0WU
HuO9 M3PhUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXf6fHVtUUN3ME2yOk44PiCwTR?= NWfrWGFOW0GQR1XS
SW962 MkPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHZfIVKSzVyPUK2Mlc3KG6P MWLTRW5ITVJ?
RS4-11 M4nNRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\STWM2OD1{Nj65NUBvVQ>? NHGwTJFUSU6JRWK=
NCI-H292 M4PQ[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M37HUGlEPTB;Mkegcm0> NWPCPHZ5W0GQR1XS
DB NX31VJNDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYPvWo9zUUN3ME2yO{4{PiCwTR?= NUH5No1SW0GQR1XS
SW1088 MnflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV3JR|UxRTJ6LkK5JI5O Mn7DV2FPT0WU
A204 NVvBWmpVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn36TWM2OD1{OD60O{BvVQ>? MV;TRW5ITVJ?
A3-KAW M{LaVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnVcoFKSzVyPUK4MlY1KG6P MmH2V2FPT0WU
MV-4-11 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLVTWM2OD1{OD63JI5O NEPyZ5pUSU6JRWK=
ES1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvn[WF{UUN3ME2yPE45PCCwTR?= NFPGSJRUSU6JRWK=
ONS-76 NIPmXmFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVTJR|UxRTJ7LkC1JI5O MVHTRW5ITVJ?
D-263MG NFXMRWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTJ7LkO1JI5O NIrKcpdUSU6JRWK=
U-2-OS MmCyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrLTWM2OD1{OT61JI5O MnLwV2FPT0WU
T98G MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1TwUGlEPTB;MkmuPFghdk1? NVfmdWZlW0GQR1XS
GI-ME-N NWfLOm9OT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE[yV5FKSzVyPUK5MlkyKG6P M{HBTXNCVkeHUh?=
BHT-101 M2nsfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFf2R|RKSzVyPUOwMlA2KG6P MXzTRW5ITVJ?
NOS-1 MnfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF:1O41KSzVyPUOwMlEzKG6P MVvTRW5ITVJ?
AsPC-1 NFzlbllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M16z[2lEPTB;M{CuNkBvVQ>? NFe0[YJUSU6JRWK=
QIMR-WIL MoXTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XVUGlEPTB;M{CuOkBvVQ>? NGfCVoVUSU6JRWK=
JVM-3 NVTtSWN[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7yOoU4UUN3ME2zNE45OyCwTR?= MWnTRW5ITVJ?
KU-19-19 M{nIUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXRRmJKSzVyPUOxMlE{KG6P MXrTRW5ITVJ?
OVCAR-8 Ml7uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTNzLkK2JI5O M4nGWHNCVkeHUh?=
BEN MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLxTWM2OD1|MT62N{BvVQ>? Mnq3V2FPT0WU
BE-13 NXPJTpU1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmHGTWM2OD1|MT64NkBvVQ>? NIDzWI1USU6JRWK=
EW-18 NXW3d5RpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnzbIdDUUN3ME2zNU45PiCwTR?= NXXxWmZMW0GQR1XS
ECC10 Mm\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn[1TWM2OD1|MT65OUBvVQ>? M1TsdXNCVkeHUh?=
CTV-1 MmjqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoThTWM2OD1|Mj64NkBvVQ>? NVXsOIF4W0GQR1XS
COLO-800 MkPpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWPJR|UxRTN{LkmyJI5O MkfQV2FPT0WU
A2058 NILxc2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4SwT2lEPTB;M{OuNlUhdk1? MkfSV2FPT0WU
VM-CUB-1 MoDVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXuSlBDUUN3ME2zN{41OyCwTR?= MVPTRW5ITVJ?
Ca9-22 NEPsbppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HyT2lEPTB;M{OuOVUhdk1? NULadWF6W0GQR1XS
COLO-684 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LmXGlEPTB;M{OuOVghdk1? NIK1cZpUSU6JRWK=
RPMI-8226 NEfWZ3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mmr6TWM2OD1|Mz64NkBvVQ>? M1Tnb3NCVkeHUh?=
SK-NEP-1 NIPHWHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTN2LkG1JI5O MmruV2FPT0WU
Becker MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjLWW5KSzVyPUO0MlIyKG6P NWLvS4VGW0GQR1XS
NCI-H28 M{LXbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTN2LkS0JI5O NXjBc21{W0GQR1XS
CAL-120 NEG5doRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDjdIVKSzVyPUO0MlczKG6P M2\oSHNCVkeHUh?=
MDA-MB-157 NH\xS5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF;TOo9KSzVyPUO1MlQyKG6P NGjoXJNUSU6JRWK=
OVCAR-5 NHT0Um9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2naSmlEPTB;M{WuOFchdk1? NWDvRpFnW0GQR1XS
LAMA-84 MlP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3ETWM2OD1|NT64O{BvVQ>? NFmxPZpUSU6JRWK=
CAKI-1 M4DDZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH;T[3BKSzVyPUO2MlQ{KG6P NUH3bFI5W0GQR1XS
Daoy NGi3SYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXWwdpVIUUN3ME2zOk44KG6P MoHpV2FPT0WU
CAL-62 NGmxZ25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF\j[ZhKSzVyPUO2Mlg3KG6P NWq2PHFtW0GQR1XS
8-MG-BA MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLaTWM2OD1|Nz6yOUBvVQ>? M1LpfHNCVkeHUh?=
8505C M1;qU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;SW4hIUUN3ME2zO{42OSCwTR?= M3fHRXNCVkeHUh?=
LNCaP-Clone-FGC NEHDTnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvRTWM2OD1|Nz61PUBvVQ>? MUTTRW5ITVJ?
CAL-39 NEXiVXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnBe4FpUUN3ME2zO{46KG6P MXXTRW5ITVJ?
MN-60 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTN5Lkm2JI5O NGP5fZZUSU6JRWK=
RKO MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7hWZNOUUN3ME2zPE4{OyCwTR?= M3jiUnNCVkeHUh?=
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HCC1419 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2GwOWlEPTB;M{iuO|Ehdk1? MmP0V2FPT0WU
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KYSE-180 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2TWSWlEPTB;NE[uNVchdk1? M4XrdHNCVkeHUh?=
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SF539 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoqyTWM2OD13Mj6zOUBvVQ>? M4LuenNCVkeHUh?=
RPMI-2650 MkLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\QTWM2OD13Mj62PUBvVQ>? M4\5d3NCVkeHUh?=
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KOSC-2 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1:yS2lEPTB;NkmuPVchdk1? NHPPeWNUSU6JRWK=
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C8166 MkLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrkTFl1UUN3ME2yMlY{Ozl{IN88US=> MVvTRW5ITVJ?
COLO-678 NFzuTY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPYTmNKSzVyPUKuPFM4PjhizszN NVjuN5hqW0GQR1XS
SK-N-DZ Mkm5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjC[IhKSzVyPUKuPFY{QDFizszN M3TaSXNCVkeHUh?=
NCI-H82 M2f6[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLEXGF[UUN3ME2yMlkxOzZ7IN88US=> M{S4UXNCVkeHUh?=
JVM-2 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\LTGlEPTB;Mz6wN|E5QCEQvF2= NHzzc45USU6JRWK=
SW1116 M3qxfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUH6cmFWUUN3ME2zMlA2PDFzIN88US=> M3;3[nNCVkeHUh?=
MDA-MB-453 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTNwMUC0N|kh|ryP NW\y[JNxW0GQR1XS
Calu-6 MmX1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlr4TWM2OD1|LkG5PVch|ryP MnrDV2FPT0WU
SHP-77 MlzIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXHZXhKSzVyPUOuOVI5KM7:TR?= NYT4R4JFW0GQR1XS
Capan-2 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTRwM{K1PFEh|ryP M{XHeHNCVkeHUh?=
SW948 MmXRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLGT2FJUUN3ME20Mlc1Pzd7IN88US=> MYHTRW5ITVJ?
HDLM-2 M{\mVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljPTWM2OD13LkC3O|I2KM7:TR?= NWL3Z24{W0GQR1XS
LAN-6 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETPcm9KSzVyPU[uNlE1QTVizszN MWTTRW5ITVJ?
LU-135 MkLaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTZwNEOwO|ch|ryP NF7qXIlUSU6JRWK=
T84 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonoTWM2OD14Lkm4OlQh|ryP NHiwVXdUSU6JRWK=
CAPAN-1 NWLYbG5zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTdwNkKyN|Mh|ryP NUfqO5BnW0GQR1XS
SW1417 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3i[GV[UUN3ME23MlkyPzNzIN88US=> MoiyV2FPT0WU
BALL-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRThwNUC0NFkh|ryP Ml\KV2FPT0WU
HT-29 MoDYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTlwMEe1PVkh|ryP MoXQV2FPT0WU
C3A MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfpXZJ1UUN3ME25Mlg5Ozl2IN88US=> MlPBV2FPT0WU
NCI-H1993 NWHLfnZqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\0cGlEPTB;MUCuOVA5OSEQvF2= NUTMU21qW0GQR1XS
SK-MEL-1 MoDHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTFzLk[yPFkh|ryP MU\TRW5ITVJ?
DU-145 MlLmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX[5O444UUN3ME2xOE42ODV{IN88US=> MYLTRW5ITVJ?
KP-N-YN M4ewXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTF2LkWxNFMh|ryP MlqyV2FPT0WU
CCRF-CEM M2XqTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rKU2lEPTB;MUSuO|gxQSEQvF2= MXHTRW5ITVJ?
ZR-75-30 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVLJR|UxRTF4LkOzNFMh|ryP NX\x[ZhvW0GQR1XS
A673 NWT6UYRzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DxV2lEPTB;MkCuOVUxPyEQvF2= M1;IVXNCVkeHUh?=
K-562 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjzUoM2UUN3ME2yPE41OTh|IN88US=> MnL4V2FPT0WU

... 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 individually and in order:
NMP+polyethylene glycol 300 (10+90, v+v)		 30 mg/mL

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

Chemical Information

Molecular Weight 469.55
Formula

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

Bio Calculators

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

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

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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)

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

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

Tech Support

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

Handling Instructions

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

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