Dactolisib (BEZ235, NVP-BEZ235)

Catalog No.S1009

Dactolisib (BEZ235, NVP-BEZ235) Chemical Structure

Molecular Weight(MW): 469.55

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

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Cited by 88 Publications

11 Customer Reviews

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

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

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

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

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

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

     

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

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

     

     

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

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

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

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

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

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

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

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

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

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

     

     

     

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

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

     

     

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

  •  

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

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

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

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

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei MWrBcpRqdWmlcn;ibYFtKEG|c3H5 MkjpNVghcA>? M1\F[mROW09? M4O1PWFvfGm2conwZY5we2:vYXygZYN1cX[rdImge4l1cCCHQ{WwJI9nKDBwMECyOUDPxE1? M3rzcVI1QDB3OUS2
MCF7 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGHnOIIxNjBzLUGwNEDPxE1? MUO0PEBp NY\EW2xSTE2VTx?= NEnNcIpKSzVyPUCuO|Mh|ryP M4DIWFI{QDdzOUC0
HCT116 NUHwOnBVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknmNE4xOS1zMECg{txO Mle1OFghcA>? M1jQOGROW09? NX[5NVdtUUN3ME2xMlE3KM7:TR?= Mn\uNlM5PzF7MES=
U87MG NUPW[XI1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTRNE4xOS1zMECg{txO MmexOFghcA>? NGTTS5JFVVOR M3O1[mlEPTB;MT6zNkDPxE1? M1LkV|I{QDdzOUC0
HBC4 NVjafHR[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY[wMlAyNTFyMDFOwG0> MUG0PEBp MnviUI9oKEeLNUC9MVgvPjFiTR?= MX:yNlM{PjJ2Nh?=
BSY1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXv0dY8zOC5yMT2xNFAh|ryP NG\hNFI1QCCq MYfMc4chT0l3ME2tPE41QCCP M{[4W|IzOzN4MkS2
HBC5 NXHJSVA{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjpXnMxNjBzLUGwNEDPxE1? NYDqcYprPDhiaB?= NIT3emlNd2diR1m1NF0uPy56NzDN MlrzNlI{OzZ{NE[=
MCF7 NHX6RZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jkN|AvODFvMUCwJO69VQ>? NYXQWZFQPDhiaB?= M2jtV2xw\yCJSUWwQU05NjF4IF2= NX;nc21wOjJ|M{[yOFY>
MDA-MB-231 NGntVGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml3vNE4xOS1zMECg{txO M1X6bVQ5KGh? MV3Mc4chT0l3ME2tPE4xQSCP NVq0emkxOjJ|M{[yOFY>
U251 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{naZVAvODFvMUCwJO69VQ>? NX75dlBwPDhiaB?= MWHMc4chT0l3ME2tO{43PiCP MUSyNlM{PjJ2Nh?=
SF268 M{Sxfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEG5S3YxNjBzLUGwNEDPxE1? Mm\4OFghcA>? MXvMc4chT0l3ME2tO{46OiCP MkTTNlI{OzZ{NE[=
SF295 NWfYWVIyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVTqOmpoOC5yMT2xNFAh|ryP NFG0c|k1QCCq NX3R[Iw3VG:pIFfJOVA:NThwM{GgUS=> M4fZNFIzOzN4MkS2
SF539 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzrNE4xOS1zMECg{txO MXm0PEBp MY\Mc4chT0l3ME2tPE42QSCP Mn;XNlI{OzZ{NE[=
SNB75 MmK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\FfoYxNjBzLUGwNEDPxE1? MXe0PEBp NYnzNm1qVG:pIFfJOVA:NThwNUigUS=> MYOyNlM{PjJ2Nh?=
SNB78 M2DmV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFv6blAxNjBzLUGwNEDPxE1? MXK0PEBp M3zJb2xw\yCJSUWwQU05NjZ3IF2= M{mx[FIzOzN4MkS2
HCC2998 M1PxfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;VWnNNOC5yMT2xNFAh|ryP MXW0PEBp MXnMc4chT0l3ME2tPE4xPSCP MV2yNlM{PjJ2Nh?=
KM12 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHXQSlAxNjBzLUGwNEDPxE1? MnvNOFghcA>? NVP2SHlrVG:pIFfJOVA:NTdwNUSgUS=> M2ftO|IzOzN4MkS2
HT-29 M1K4U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnFNE4xOS1zMECg{txO NYrrXWtxPDhiaB?= NHH6TVNNd2diR1m1NF0uPy55NTDN MXSyNlM{PjJ2Nh?=
HCT15 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2LLTFAvODFvMUCwJO69VQ>? MUO0PEBp NGTkb3lNd2diR1m1NF0uQC5yMzDN M2fVRVIzOzN4MkS2
HCT116 NHPSWIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYiwMlAyNTFyMDFOwG0> NX;DNmhoPDhiaB?= M3TIfWxw\yCJSUWwQU04NjZzIF2= NILPc5UzOjN|NkK0Oi=>
NCI-H23 M2\TdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUWwMlAyNTFyMDFOwG0> MnXZOFghcA>? MVfMc4chT0l3ME2tO{43PCCP NGG2NFgzOjN|NkK0Oi=>
NCI-H226 Mn[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm\jNE4xOS1zMECg{txO MoDROFghcA>? MXLMc4chT0l3ME2tPE41PCCP NXe3VG5xOjJ|M{[yOFY>
NCI-H522 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWqwMlAyNTFyMDFOwG0> NIjTTWw1QCCq MkHOUI9oKEeLNUC9MVgvPDViTR?= MWqyNlM{PjJ2Nh?=
NCI-H438 M2P0UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUCwMlAyNTFyMDFOwG0> NY\6SVB6PDhiaB?= Ml7rUI9oKEeLNUC9MVgvOTFiTR?= NITVV2ozOjN|NkK0Oi=>
A549 M3f3VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4jnWFAvODFvMUCwJO69VQ>? NEHUeIg1QCCq NFizNnRNd2diR1m1NF0uQC5yNzDN MUKyNlM{PjJ2Nh?=
DMS273 M2jSTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfDNE4xOS1zMECg{txO NIHVWYM1QCCq NXrZVGs5VG:pIFfJOVA:NTdwOECgUS=> MlvPNlI{OzZ{NE[=
DMS114 NHHiTWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPlZnkxNjBzLUGwNEDPxE1? NFrmRnk1QCCq M{K0Smxw\yCJSUWwQU05NjN7IF2= MWmyNlM{PjJ2Nh?=
LOXIMVI M2X1bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXywMlAyNTFyMDFOwG0> MYq0PEBp MVrMc4chT0l3ME2tPE43PiCP M4W0ZlIzOzN4MkS2
OVCAR3 NY\2clVMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nWTVAvODFvMUCwJO69VQ>? NInrOpI1QCCq NGPB[VRNd2diR1m1NF0uQC5zNzDN MViyNlM{PjJ2Nh?=
OVCAR4 NV7Lb2pHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PQbFAvODFvMUCwJO69VQ>? NHT6fms1QCCq MmrDUI9oKEeLNUC9MVgvPThiTR?= M37VOlIzOzN4MkS2
OVCAR5 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHR[poxNjBzLUGwNEDPxE1? MUC0PEBp M4K3S2xw\yCJSUWwQU04NjV5IF2= MW[yNlM{PjJ2Nh?=
OVCAR8 Ml;VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn7mNE4xOS1zMECg{txO M37hclQ5KGh? MWPMc4chT0l3ME2tO{45PCCP MoTtNlI{OzZ{NE[=
SKOV3 M2npcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYC0VoNEOC5yMT2xNFAh|ryP MoLEOFghcA>? MVXMc4chT0l3ME2tPE41OSCP MYqyNlM{PjJ2Nh?=
RXF631L NGfRWmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\mfHhlOC5yMT2xNFAh|ryP M1jpdVQ5KGh? MnTaUI9oKEeLNUC9MVgvOjFiTR?= MnXmNlI{OzZ{NE[=
ACHN NHvpWmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWCwMlAyNTFyMDFOwG0> NGD0[Yg1QCCq MWPMc4chT0l3ME2tO{46PSCP MUGyNlM{PjJ2Nh?=
St-4 NW\EcVFWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3fwOlAvODFvMUCwJO69VQ>? NX7CfHBOPDhiaB?= Ml:0UI9oKEeLNUC9MVcvPDdiTR?= NVn1NHF6OjJ|M{[yOFY>
MKN1 MlG2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH22clMxNjBzLUGwNEDPxE1? M2DCRlQ5KGh? MVzMc4chT0l3ME2tPE41OSCP NHLXfo0zOjN|NkK0Oi=>
MKN7 NH70Z5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVOwMlAyNTFyMDFOwG0> M4jQNlQ5KGh? NIKxPGZNd2diR1m1NF0uPy54ODDN NFTCb3czOjN|NkK0Oi=>
MKN28 NWDkUXFDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHvUTVcxNjBzLUGwNEDPxE1? NWDu[oxGPDhiaB?= M37vXWxw\yCJSUWwQU04NjB5IF2= NVrFdGp3OjJ|M{[yOFY>
MKN45 NFPjWHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWjPb4FbOC5yMT2xNFAh|ryP Mkf2OFghcA>? NVzuZlR6VG:pIFfJOVA:NThwM{SgUS=> NHn4VoUzOjN|NkK0Oi=>
MKN74 NWjUPIpZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TzVVAvODFvMUCwJO69VQ>? MYW0PEBp Mn;QUI9oKEeLNUC9MVcvPDJiTR?= M3HXOFIzOzN4MkS2
DU145 NGrTcYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\rPVAvODFvMUCwJO69VQ>? M3rBSVQ5KGh? MlHOUI9oKEeLNUC9MVgvOTZiTR?= NXu1fXM3OjJ|M{[yOFY>
PC3 NVLqSWNiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLyN4lHOC5yMT2xNFAh|ryP NVXY[IdUPDhiaB?= MX\Mc4chT0l3ME2tPE43PiCP Ml3oNlI{OzZ{NE[=
Trypanosoma brucei brucei NIXJS3ZHfW6ldHnvckBCe3OjeR?= NIXRS3czODBibl2= MnvmNVIhcA>? NV72Z2Y2TE2VTx?= MoDsSIVkemWjc3WgbY4heGixc4Doc5Rq\HmuIHnuc5NqfG:uIIDoc5NxcGG2ZTDs[ZZmdA>? MXGyOFgxPTl2Nh?=
Trypanosoma brucei brucei MkXBSpVv[3Srb36gRZN{[Xl? MWmxPEBp NIXaXYtFVVOR M{HBd2lvcGmkaYTpc44hd2ZicnXj[ZB1d3JvbXXkbYF1\WRiZX7kc4N6fG:|aYOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5idILhcpNn\XK{aX6geZB1[Wun MlXsNlQ5ODV7NE[=
Trypanosoma brucei brucei MknDSpVv[3Srb36gRZN{[Xl? MWqyNFAhdk1? M1H6SVEzKGh? MXLEUXNQ Mn3PSYZn\WO2IH;uJJNxcGmwZ3;tfYxmcW5ibHX2[Yw> NGTZZokzPDhyNUm0Oi=>
Trypanosoma brucei brucei M3\OVGZ2dmO2aX;uJGF{e2G7 M1jPNFIxOCCwTR?= MWmxNkBp Ml3BSG1UVw>? NVfzXZpJTW[oZXP0JI9vKHCqb4PwbIF1cWS7bHPoc4xqdmVibHX2[Yw> NF7QUmwzPDhyNUm0Oi=>
UM-UC-3 NY\6Tlh6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTNzNTDwUS=> NHPOVIlUSU6JRWK=
SBC-1 M3LMWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTsUnRJUUN3ME23OFIheE1? M3SyW3NCVkeHUh?=
MKN1 NI\0c|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rPN2lEPTB;Mj64JI5O NIrPemtUSU6JRWK=
NCI-H720 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnXSTWM2OD1|LkW3JI5O MVTTRW5ITVJ?
BFTC-909 M3vUeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7ZR5k5UUN3ME2zMlcyKG6P NELoWHZUSU6JRWK=
BPH-1 MlLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWnJR|UxRTRwN{[gcm0> M1;4cHNCVkeHUh?=
PC-3 NH;nO|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTVwMEmgcm0> MVTTRW5ITVJ?
AN3-CA Mlr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnv3TWM2OD13LkW2JI5O MnrOV2FPT0WU
HN NWPPU|dZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITabnVKSzVyPUWuPVYhdk1? NULURmRrW0GQR1XS
HCC2218 NFf2NphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3S3W2lEPTB;Nj62NUBvVQ>? NIP3blRUSU6JRWK=
KP-4 M4j2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;ROJRDUUN3ME23JI5O MVfTRW5ITVJ?
LU-139 NFnyWHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PPdWlEPTB;Nz63O{BvVQ>? NGfRWGJUSU6JRWK=
ETK-1 NHfseGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojJTWM2OD15Lki4JI5O MYTTRW5ITVJ?
Ramos-2G6-4C10 MoPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIH1VHhKSzVyPUiuOFkhdk1? NHezTnRUSU6JRWK=
MHH-PREB-1 NGHuSIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;qZ2lEPTB;OT6xNkBvVQ>? Ml;lV2FPT0WU
DU-4475 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTlwNESgcm0> M1rpNnNCVkeHUh?=
NCI-H1666 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jlTWlEPTB;OT63NUBvVQ>? MoHjV2FPT0WU
CAMA-1 NHK5cZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTlwODDuUS=> M17FcXNCVkeHUh?=
TYK-nu MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fObWlEPTB;OT65OEBvVQ>? NV65RWxsW0GQR1XS
MFE-280 NGnBRWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoDjTWM2OD17Lkm5JI5O M4PsdnNCVkeHUh?=
A549 NIPoR49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVK0S5RzUUN3ME2xNE4yPCCwTR?= NETsPZdUSU6JRWK=
769-P NEXafIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rIPGlEPTB;MUCuOFQhdk1? M2D1TXNCVkeHUh?=
L-363 M4Xzd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH;VZ5JKSzVyPUGwMlY6KG6P M{TDVXNCVkeHUh?=
ES8 Mmf5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4nWTGlEPTB;MUCuPUBvVQ>? NWfac4VPW0GQR1XS
PA-1 M1:2O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\ONmlEPTB;MUGuPFIhdk1? MV3TRW5ITVJ?
Mewo NIPiRZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3EPZV2UUN3ME2xNU46QSCwTR?= Mk\mV2FPT0WU
HSC-3 NYC0dnljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MULJR|UxRTF{LkKxJI5O MlG5V2FPT0WU
H4 MnftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHZTWM2OD1zMj62O{BvVQ>? NGTZ[4NUSU6JRWK=
BB65-RCC NUXzeFZIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\GVZpKSzVyPUGyMlczKG6P NFLTNHpUSU6JRWK=
NCI-H1793 NFHMdItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnz5TWM2OD1zMj64NkBvVQ>? MUDTRW5ITVJ?
KARPAS-45 M2fYWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTXSWNKSzVyPUGzMlUyKG6P MmC4V2FPT0WU
GCT NV3zXFNqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzRbJdKSzVyPUGzMlY5KG6P NEXGbY9USU6JRWK=
EoL-1 MnTnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH;qcIdKSzVyPUGzMlk{KG6P MoTXV2FPT0WU
LB2241-RCC NInBeWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HqemlEPTB;MUSuNFEhdk1? Mo[3V2FPT0WU
ES5 MmflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTF2Lke0JI5O NYfxXYJpW0GQR1XS
LOXIMVI NUfRfWtlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTF2Lkm5JI5O M1nKTHNCVkeHUh?=
COR-L105 NUS4[2E2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYrJR|UxRTF3LkC0JI5O NEXWNJpUSU6JRWK=
P12-ICHIKAWA MmnsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGSxd2xKSzVyPUG1MlEhdk1? M{W3VHNCVkeHUh?=
CHL-1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vvcGlEPTB;MUWuOFUhdk1? MUHTRW5ITVJ?
VMRC-RCZ NHPRUVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvKZ4JKSzVyPUG1MlY{KG6P MYHTRW5ITVJ?
HH MnntS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRTF3Lkegcm0> M3fOR3NCVkeHUh?=
NUGC-3 NGrO[2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLT[4NKSzVyPUG2MlM1KG6P M{fPZ3NCVkeHUh?=
EGI-1 NVvnW4dwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M370Z2lEPTB;MU[uOFMhdk1? NEDHSJpUSU6JRWK=
OS-RC-2 MkDUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fHRWlEPTB;MU[uOFchdk1? NXO5[FhUW0GQR1XS
MOLT-16 MoHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnyWHlKSzVyPUG3MlE2KG6P MXrTRW5ITVJ?
NCI-H209 M{LZPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTF5LkK5JI5O NFzGVZFUSU6JRWK=
697 MmXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjPZ|ZKSzVyPUG3MlQ{KG6P M1rzPXNCVkeHUh?=
D-56MG Ml7ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\meWNVUUN3ME2xO{43QSCwTR?= MYHTRW5ITVJ?
VA-ES-BJ NELJOXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHznS3FKSzVyPUG3Mlg{KG6P MVjTRW5ITVJ?
EW-16 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF7EcoNKSzVyPUG4MlA1KG6P M{jB[HNCVkeHUh?=
HGC-27 M4i1RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\sb2FKSzVyPUG4MlA3KG6P M4r3N3NCVkeHUh?=
ES7 Mn3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\qemZKSzVyPUG4MlA6KG6P MWDTRW5ITVJ?
HuH-7 M4fNdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFviVIFKSzVyPUG4MlQhdk1? NHfSbXNUSU6JRWK=
BCPAP NGT3ZWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mmm2TWM2OD1zOD62OUBvVQ>? M364TXNCVkeHUh?=
SW1710 NEnub3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTF6LkeyJI5O NWTPcINlW0GQR1XS
IST-MEL1 MlTFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULmXldnUUN3ME2xPE44PyCwTR?= NXHue|BPW0GQR1XS
SF295 NXzMU2V3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIDm[4pKSzVyPUG4Mlk{KG6P MYPTRW5ITVJ?
RPMI-7951 Moe5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmm4TWM2OD1zOT6yPEBvVQ>? M{PJ[3NCVkeHUh?=
SF126 Ml3ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTF7LkSxJI5O NEi0PYJUSU6JRWK=
GAMG NGP4OmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXlWlJ2UUN3ME2xPU41QCCwTR?= NGrBOZBUSU6JRWK=
KNS-81-FD MlzpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DDSWlEPTB;MUmuOVQhdk1? MnXHV2FPT0WU
RT-112 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXX6[FlpUUN3ME2xPU43PiCwTR?= MUfTRW5ITVJ?
DEL NIDhTY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPpb21KSzVyPUKwMlQ6KG6P NF\qU2dUSU6JRWK=
CGTH-W-1 NX2zcYJjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzVTWM2OD1{MD62N{BvVQ>? M2HweHNCVkeHUh?=
HOS MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTJzLkC2JI5O NWTiOopRW0GQR1XS
ES4 NEH4PWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmXkTWM2OD1{MT6wPEBvVQ>? NFvQOodUSU6JRWK=
RXF393 NWj1c5RjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MornTWM2OD1{MT60OUBvVQ>? MlXXV2FPT0WU
NCI-H2030 NIX1OZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPEbZJKSzVyPUKxMlUzKG6P MlixV2FPT0WU
YH-13 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrpTWM2OD1{MT64PEBvVQ>? NHX2XGJUSU6JRWK=
HT-1080 NVHRVIJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjRfWRSUUN3ME2yNU46OyCwTR?= MUDTRW5ITVJ?
NCI-SNU-1 NGPoUFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HLWWlEPTB;MkGuPVUhdk1? NX6zTnRxW0GQR1XS
G-402 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTJ{LkG2JI5O MYTTRW5ITVJ?
786-0 NY\CWGg6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\QXWlEPTB;MkKuNlkhdk1? NVTYSWEyW0GQR1XS
ME-180 NVv6NIFPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEX0TpRKSzVyPUKyMlQ{KG6P NV7rTJo2W0GQR1XS
NB69 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XqPGlEPTB;MkKuOVMhdk1? M3;kTnNCVkeHUh?=
J-RT3-T3-5 MkP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nGU2lEPTB;MkKuPVYhdk1? MojuV2FPT0WU
TGBC1TKB M4LpTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXKTWM2OD1{Mz6wOUBvVQ>? MYLTRW5ITVJ?
SW780 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\zRWJlUUN3ME2yN{4yOyCwTR?= NUTQ[5VHW0GQR1XS
MG-63 NHm3VmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml;UTWM2OD1{Mz60OUBvVQ>? MWTTRW5ITVJ?
BV-173 NV;QbG1lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfFTY9KSzVyPUKzMlg4KG6P NXTYZVJOW0GQR1XS
CAL-51 Ml3MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTJ|Lki5JI5O NF7xR21USU6JRWK=
A375 NEHxeYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1L5XmlEPTB;MkOuPVMhdk1? NH7NSWVUSU6JRWK=
MEL-HO NYTuXmZlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoS2TWM2OD1{ND6wOEBvVQ>? MnGyV2FPT0WU
EFO-27 M3rQUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXX1U|RTUUN3ME2yOE4{OyCwTR?= MoXQV2FPT0WU
Hs-578-T MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJ2LkW4JI5O M37n[XNCVkeHUh?=
NBsusSR M37wdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLaTWM2OD1{ND62JI5O Mo[3V2FPT0WU
CTB-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVzi[5lSUUN3ME2yOE43PyCwTR?= MnXLV2FPT0WU
FTC-133 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jqU2lEPTB;MkWuNUBvVQ>? NH\iWJNUSU6JRWK=
MOLT-4 NIC1UlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWT5d3NNUUN3ME2yOU4yOiCwTR?= MYTTRW5ITVJ?
HO-1-N-1 NEnCXI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1r3[mlEPTB;MkWuNVUhdk1? Moi0V2FPT0WU
ES3 NHHRW3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX7TSlYyUUN3ME2yOU4zOiCwTR?= MlrvV2FPT0WU
TI-73 NF33eI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJR|UxRTJ3LkK4JI5O M1\5enNCVkeHUh?=
MPP-89 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3G0XGlEPTB;MkWuN|Ihdk1? NYHERZZiW0GQR1XS
KYSE-150 MlzYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nCTmlEPTB;MkWuPFkhdk1? MXrTRW5ITVJ?
LXF-289 NXXrVGc2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\NPWVoUUN3ME2yOk4xPCCwTR?= NWrtRpBRW0GQR1XS
SK-LU-1 NGjQdGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2ToNGlEPTB;Mk[uNVchdk1? M4TIR3NCVkeHUh?=
HOP-92 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\CeVFoUUN3ME2yOk41QCCwTR?= NELhSVhUSU6JRWK=
HuO9 NVq3TlRtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYq1TFA6UUN3ME2yOk44PiCwTR?= NViyeYlmW0GQR1XS
SW962 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4f3XGlEPTB;Mk[uO|Yhdk1? NFPaSohUSU6JRWK=
RS4-11 Ml3VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULZOXFiUUN3ME2yOk46OSCwTR?= NIfHdHRUSU6JRWK=
NCI-H292 NHnW[W1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mni3TWM2OD1{NzDuUS=> NHzCOHBUSU6JRWK=
DB NFv5VlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkPDTWM2OD1{Nz6zOkBvVQ>? MUjTRW5ITVJ?
SW1088 NUDGS|dWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTJ6LkK5JI5O MXvTRW5ITVJ?
A204 M4LXeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTJ6LkS3JI5O NX[5eY8zW0GQR1XS
A3-KAW Mlf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2jDRWlEPTB;MkiuOlQhdk1? M3vPSnNCVkeHUh?=
MV-4-11 NH7pVWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTJ6Lkegcm0> M1[2N3NCVkeHUh?=
ES1 M17aOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonLTWM2OD1{OD64OEBvVQ>? MoDmV2FPT0WU
ONS-76 Mo\SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVHDZoVPUUN3ME2yPU4xPSCwTR?= NHPGTnJUSU6JRWK=
D-263MG MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrSTWM2OD1{OT6zOUBvVQ>? M4fLcHNCVkeHUh?=
U-2-OS MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37a[2lEPTB;MkmuOUBvVQ>? Mn\zV2FPT0WU
T98G NWXvOVlUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;sUmlEPTB;MkmuPFghdk1? NXe1R|ZPW0GQR1XS
GI-ME-N NI\r[IxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTJ7LkmxJI5O NVjIb|BqW0GQR1XS
BHT-101 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTNyLkC1JI5O NXPrXoE3W0GQR1XS
NOS-1 MoLsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRTNyLkGyJI5O M3jTXnNCVkeHUh?=
AsPC-1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PsdGlEPTB;M{CuNkBvVQ>? M33IXnNCVkeHUh?=
QIMR-WIL Ml7pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXLaS3RnUUN3ME2zNE43KG6P MkLQV2FPT0WU
JVM-3 NYXWOIFJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TK[WlEPTB;M{CuPFMhdk1? NV3XSmhwW0GQR1XS
KU-19-19 NVK2NJE{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofpTWM2OD1|MT6xN{BvVQ>? NELFOXlUSU6JRWK=
OVCAR-8 M13je2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HBZmlEPTB;M{GuNlYhdk1? MUfTRW5ITVJ?
BEN NXS2TZVsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjRdIZKSzVyPUOxMlY{KG6P M{HlcnNCVkeHUh?=
BE-13 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV2yPYNKUUN3ME2zNU45OiCwTR?= M1vrfXNCVkeHUh?=
EW-18 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13MeGlEPTB;M{GuPFYhdk1? NVTFN4NoW0GQR1XS
ECC10 NUD3[GdpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPTZnV5UUN3ME2zNU46PSCwTR?= MojZV2FPT0WU
CTV-1 M4TxcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3LbpdKSzVyPUOyMlgzKG6P NHOxWoFUSU6JRWK=
COLO-800 M1XwVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGP6U4tKSzVyPUOyMlkzKG6P MoDXV2FPT0WU
A2058 NX36V|hRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTN|LkK1JI5O NYS1TngyW0GQR1XS
VM-CUB-1 NF3OfZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHqTVdUUUN3ME2zN{41OyCwTR?= NVG0SlBjW0GQR1XS
Ca9-22 M{\3d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDZU2lKSzVyPUOzMlU2KG6P Mn\xV2FPT0WU
COLO-684 MoHwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnWTWM2OD1|Mz61PEBvVQ>? M4LzZnNCVkeHUh?=
RPMI-8226 M1XZVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnQVVJKSzVyPUOzMlgzKG6P NWT2RmVwW0GQR1XS
SK-NEP-1 NFWzfpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTN2LkG1JI5O M1fRSHNCVkeHUh?=
Becker MkHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRTN2LkKxJI5O M1vMcHNCVkeHUh?=
NCI-H28 M{\qcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGrDPGNKSzVyPUO0MlQ1KG6P M4DsOHNCVkeHUh?=
CAL-120 NUnnTXJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTN2LkeyJI5O NXTWdnN[W0GQR1XS
MDA-MB-157 NUHETFRkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT1bpJKSzVyPUO1MlQyKG6P Mle1V2FPT0WU
OVCAR-5 NUOwW|hjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXwTYpWUUN3ME2zOU41PyCwTR?= MlX1V2FPT0WU
LAMA-84 NYrLO5FiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDyXohKSzVyPUO1Mlg4KG6P NF\MSFNUSU6JRWK=
CAKI-1 M1P5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TLSGlEPTB;M{[uOFMhdk1? NXriNZVnW0GQR1XS
Daoy Mn\5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHYdlBKSzVyPUO2Mlchdk1? M1THe3NCVkeHUh?=
CAL-62 MmD2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1W0WmlEPTB;M{[uPFYhdk1? MljhV2FPT0WU
8-MG-BA MnXBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn;nTWM2OD1|Nz6yOUBvVQ>? MVfTRW5ITVJ?
8505C NWLVVnNXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFfVdXFKSzVyPUO3MlUyKG6P M1jYPHNCVkeHUh?=
LNCaP-Clone-FGC M13wOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGG3ZWlKSzVyPUO3MlU6KG6P NIrUU4hUSU6JRWK=
CAL-39 NELP[FRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTN5Lkmgcm0> NX30R2N[W0GQR1XS
MN-60 NITaSYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjVR2RKSzVyPUO3Mlk3KG6P Mnj4V2FPT0WU
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OAW-28 NWHzeJQ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzBWItuUUN3ME2yMlA3QTF7IN88US=> MYLTRW5ITVJ?
C8166 NVfFd21ZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mme2TWM2OD1{Lk[zN|kzKM7:TR?= MU\TRW5ITVJ?
COLO-678 M4W4Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7OTWM2OD1{LkizO|Y5KM7:TR?= MWXTRW5ITVJ?
SK-N-DZ MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJwOE[zPFEh|ryP NV\QV3JSW0GQR1XS
NCI-H82 NEfEbGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXHJR|UxRTJwOUCzOlkh|ryP NI\0[odUSU6JRWK=
JVM-2 M1;5cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUf1[lBOUUN3ME2zMlA{OTh6IN88US=> MXXTRW5ITVJ?
SW1116 NEfFZoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDZc3RKSzVyPUOuNFU1OTFizszN MnTxV2FPT0WU
MDA-MB-453 M2Pzemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1vHfWlEPTB;Mz6xNFQ{QSEQvF2= NWLnVmZjW0GQR1XS
Calu-6 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2LpbGlEPTB;Mz6xPVk4KM7:TR?= MX\TRW5ITVJ?
SHP-77 Mlu0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnHFTWM2OD1|LkWyPEDPxE1? NF\4S5hUSU6JRWK=
Capan-2 M3:1NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWexXmoxUUN3ME20MlMzPThzIN88US=> NFHxZ4FUSU6JRWK=
SW948 NGD1NVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn\wTWM2OD12Lke0O|c6KM7:TR?= MVnTRW5ITVJ?
HDLM-2 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonXTWM2OD13LkC3O|I2KM7:TR?= M2jr[nNCVkeHUh?=
LAN-6 M2HmR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTZwMkG0PVUh|ryP NUDXeFNoW0GQR1XS
LU-135 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEi1cmdKSzVyPU[uOFMxPzdizszN NYnyWGdvW0GQR1XS
T84 M133[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2Sx[GlEPTB;Nj65PFY1KM7:TR?= MlPtV2FPT0WU
CAPAN-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX60N3U1UUN3ME23MlYzOjN|IN88US=> MULTRW5ITVJ?
SW1417 MmTqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlzwTWM2OD15LkmxO|MyKM7:TR?= M{K2[HNCVkeHUh?=
BALL-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPuOG9{UUN3ME24MlUxPDB7IN88US=> MV;TRW5ITVJ?
HT-29 NHfkWW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\tcoJKSzVyPUmuNFc2QTlizszN MVHTRW5ITVJ?
C3A M{jQW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3nTWM2OD17Lki4N|k1KM7:TR?= Mn3PV2FPT0WU
NCI-H1993 M{PTUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTFyLkWwPFEh|ryP M2PWc3NCVkeHUh?=
SK-MEL-1 MoXtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTFzLk[yPFkh|ryP MVnTRW5ITVJ?
DU-145 NG\FbFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoD2TWM2OD1zND61NFUzKM7:TR?= MXnTRW5ITVJ?
KP-N-YN MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\ENGlEPTB;MUSuOVExOyEQvF2= MYPTRW5ITVJ?
CCRF-CEM MnPLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1HGfWlEPTB;MUSuO|gxQSEQvF2= NVztZY9{W0GQR1XS
ZR-75-30 MojmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHT5[3NKSzVyPUG2MlM{ODNizszN M3PSXXNCVkeHUh?=
A673 M2TzNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTJyLkW1NFch|ryP M4XIO3NCVkeHUh?=
K-562 NGH1OYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37Se2lEPTB;MkiuOFE5OyEQvF2= MnfnV2FPT0WU

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

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03373903 Active not recruiting Respiratory Tract Infections Restorbio Inc. November 15 2017 Phase 2
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.

PI3K Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID