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 MYjBcpRqdWmlcn;ibYFtKEG|c3H5 NXnwWpRbOThiaB?= MULEUXNQ Ml7KRY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? NUjDRVZPOjR6MEW5OFY>
MCF7 Ml21S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWeyc24yOC5yMT2xNFAh|ryP MVu0PEBp MoHPSG1UVw>? M{P6UWlEPTB;MD63N{DPxE1? NI\ZPXczOzh5MUmwOC=>
HCT116 NWDWRXFCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLQNE4xOS1zMECg{txO MYq0PEBp NW\rOYp{TE2VTx?= Mo[1TWM2OD1zLkG2JO69VQ>? M3S1V|I{QDdzOUC0
U87MG M{S0TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXi1T3RxOC5yMT2xNFAh|ryP MWO0PEBp NXSye4FLTE2VTx?= Mm\mTWM2OD1zLkOyJO69VQ>? NFPYOGIzOzh5MUmwOC=>
HBC4 MnrXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfFNIt[OC5yMT2xNFAh|ryP NXXCRlYyPDhiaB?= MXTMc4chT0l3ME2tPE43OSCP M1\hfVIzOzN4MkS2
BSY1 NUDBVYllT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvuNE4xOS1zMECg{txO MV20PEBp NWDGcmlKVG:pIFfJOVA:NThwNEigUS=> NUK2SGFoOjJ|M{[yOFY>
HBC5 Mk\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHKTI0xNjBzLUGwNEDPxE1? MX:0PEBp NYPGRW91VG:pIFfJOVA:NTdwOEegUS=> NHrJZpMzOjN|NkK0Oi=>
MCF7 Mmr5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7sXJUxNjBzLUGwNEDPxE1? NWLRZmloPDhiaB?= NGW0dJVNd2diR1m1NF0uQC5zNjDN NXLSeIZ6OjJ|M{[yOFY>
MDA-MB-231 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPNNE4xOS1zMECg{txO NHX6b5c1QCCq NIm4cmZNd2diR1m1NF0uQC5yOTDN MmXTNlI{OzZ{NE[=
U251 M37LWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljhNE4xOS1zMECg{txO MoP6OFghcA>? NITIbGZNd2diR1m1NF0uPy54NjDN NXyzSWpJOjJ|M{[yOFY>
SF268 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfSeotXOC5yMT2xNFAh|ryP NYfySJdvPDhiaB?= NVLyXG9[VG:pIFfJOVA:NTdwOUKgUS=> NInXNZEzOjN|NkK0Oi=>
SF295 NEm0VFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;QdFAvODFvMUCwJO69VQ>? NGfMW4M1QCCq M3PjUGxw\yCJSUWwQU05NjNzIF2= M{P4WVIzOzN4MkS2
SF539 M3HQSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzxZXQxNjBzLUGwNEDPxE1? MoHMOFghcA>? M1y3TGxw\yCJSUWwQU05NjV7IF2= NWq1Z2wyOjJ|M{[yOFY>
SNB75 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\1dI1IOC5yMT2xNFAh|ryP NVjmPIlCPDhiaB?= MWXMc4chT0l3ME2tPE42QCCP MknqNlI{OzZ{NE[=
SNB78 NXfYfZdiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkjUNE4xOS1zMECg{txO M{e2SlQ5KGh? M33kcGxw\yCJSUWwQU05NjZ3IF2= MVqyNlM{PjJ2Nh?=
HCC2998 Mk\NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TBNFAvODFvMUCwJO69VQ>? NFHXO4I1QCCq M4mzcmxw\yCJSUWwQU05NjB3IF2= MkfVNlI{OzZ{NE[=
KM12 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXLlXJFkOC5yMT2xNFAh|ryP MoHUOFghcA>? NFnPUoVNd2diR1m1NF0uPy53NDDN NW[zd4k6OjJ|M{[yOFY>
HT-29 M{S1fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\iUlAvODFvMUCwJO69VQ>? Ml\wOFghcA>? MmDrUI9oKEeLNUC9MVcvPzViTR?= M{LiXVIzOzN4MkS2
HCT15 MlXiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTOeYg{OC5yMT2xNFAh|ryP NIm2TGE1QCCq MnfjUI9oKEeLNUC9MVgvODNiTR?= MVeyNlM{PjJ2Nh?=
HCT116 NFG5eGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXGwMlAyNTFyMDFOwG0> MXu0PEBp NXPGVVNUVG:pIFfJOVA:NTdwNkGgUS=> MVOyNlM{PjJ2Nh?=
NCI-H23 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVmwMlAyNTFyMDFOwG0> MkHFOFghcA>? MXTMc4chT0l3ME2tO{43PCCP M1jiVVIzOzN4MkS2
NCI-H226 M3H2R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVqwMlAyNTFyMDFOwG0> M1nYOlQ5KGh? NFPIXHpNd2diR1m1NF0uQC52NDDN NFn3Oo0zOjN|NkK0Oi=>
NCI-H522 NYX5dWU2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3kNIgxNjBzLUGwNEDPxE1? NVXM[mhzPDhiaB?= MYjMc4chT0l3ME2tPE41PSCP MVuyNlM{PjJ2Nh?=
NCI-H438 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1nNWlAvODFvMUCwJO69VQ>? MoDIOFghcA>? MkCyUI9oKEeLNUC9MVgvOTFiTR?= MlO4NlI{OzZ{NE[=
A549 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;IcFAvODFvMUCwJO69VQ>? NFHsO3E1QCCq M1fZ[mxw\yCJSUWwQU05NjB5IF2= M{LuRVIzOzN4MkS2
DMS273 NIHMbIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX7wPWJxOC5yMT2xNFAh|ryP M4K2W|Q5KGh? MY\Mc4chT0l3ME2tO{45OCCP NIHxenUzOjN|NkK0Oi=>
DMS114 NF3SfopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLqd4kxOC5yMT2xNFAh|ryP NXSxZWpxPDhiaB?= MXXMc4chT0l3ME2tPE4{QSCP MVyyNlM{PjJ2Nh?=
LOXIMVI MnTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vPcFAvODFvMUCwJO69VQ>? MYC0PEBp M3PkO2xw\yCJSUWwQU05NjZ4IF2= MVOyNlM{PjJ2Nh?=
OVCAR3 NGq5cmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzLNlQxNjBzLUGwNEDPxE1? MXS0PEBp MknmUI9oKEeLNUC9MVgvOTdiTR?= NYi2VXdFOjJ|M{[yOFY>
OVCAR4 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13USVAvODFvMUCwJO69VQ>? M3vwfFQ5KGh? NGDKcHJNd2diR1m1NF0uQC53ODDN NXzTO2Z4OjJ|M{[yOFY>
OVCAR5 NX[4R3JtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXfyUXVsOC5yMT2xNFAh|ryP NGK2dIw1QCCq NXXzdHJTVG:pIFfJOVA:NTdwNUegUS=> MmHkNlI{OzZ{NE[=
OVCAR8 NFfjXYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjpelIxNjBzLUGwNEDPxE1? MnPKOFghcA>? NFezXXdNd2diR1m1NF0uPy56NDDN MXqyNlM{PjJ2Nh?=
SKOV3 MoO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU[wMlAyNTFyMDFOwG0> MmfQOFghcA>? MortUI9oKEeLNUC9MVgvPDFiTR?= MmjyNlI{OzZ{NE[=
RXF631L MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF[1RYoxNjBzLUGwNEDPxE1? MmTlOFghcA>? MnHlUI9oKEeLNUC9MVgvOjFiTR?= NULBd4I3OjJ|M{[yOFY>
ACHN M3PWXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVOwMlAyNTFyMDFOwG0> NUXM[4c{PDhiaB?= M2G0S2xw\yCJSUWwQU04Njl3IF2= M2[1cVIzOzN4MkS2
St-4 M2DEfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3sSHU4OC5yMT2xNFAh|ryP MYS0PEBp M{HSdmxw\yCJSUWwQU04NjR5IF2= NXT2VIU3OjJ|M{[yOFY>
MKN1 NUjrVWpmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUKwMlAyNTFyMDFOwG0> NE\5S201QCCq NG[4R4RNd2diR1m1NF0uQC52MTDN NVfFWnpqOjJ|M{[yOFY>
MKN7 MofMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUG0WXR7OC5yMT2xNFAh|ryP NEnXeow1QCCq NGHaOVZNd2diR1m1NF0uPy54ODDN MkDKNlI{OzZ{NE[=
MKN28 NWn0b2szT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;kdFAvODFvMUCwJO69VQ>? M1flbVQ5KGh? NW\Sb2VsVG:pIFfJOVA:NTdwMEegUS=> MnS0NlI{OzZ{NE[=
MKN45 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHj3bHIxNjBzLUGwNEDPxE1? NFi4SmI1QCCq M2fwfWxw\yCJSUWwQU05NjN2IF2= MWSyNlM{PjJ2Nh?=
MKN74 NFz5PJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjyVmYxNjBzLUGwNEDPxE1? NWrkSY8zPDhiaB?= NHfuZppNd2diR1m1NF0uPy52MjDN MVKyNlM{PjJ2Nh?=
DU145 MkLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4XqfFAvODFvMUCwJO69VQ>? Mkj3OFghcA>? NUnwN|NyVG:pIFfJOVA:NThwMU[gUS=> M3:5ZlIzOzN4MkS2
PC3 MonIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MViwMlAyNTFyMDFOwG0> MmTTOFghcA>? MnjUUI9oKEeLNUC9MVgvPjZiTR?= NXLuT3hZOjJ|M{[yOFY>
Trypanosoma brucei brucei NFryTHlHfW6ldHnvckBCe3OjeR?= MVSyNFAhdk1? MWqxNkBp NXPCNYRjTE2VTx?= MWDE[YNz\WG|ZTDpckBxcG:|cHjveIllgWxiaX7vd4l1d2xicHjvd5Bp[XSnIHzleoVt MUSyOFgxPTl2Nh?=
Trypanosoma brucei brucei MmW1SpVv[3Srb36gRZN{[Xl? MWexPEBp NEfJVHJFVVOR MU\Jcohq[mm2aX;uJI9nKHKnY3XweI9zNW2nZHnheIVlKGWwZH;jfZRwe2m|IHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKHS{YX7z[oVzemmwIIXweIFs\Q>? NIC0S4wzPDhyNUm0Oi=>
Trypanosoma brucei brucei NWOxTWZtTnWwY4Tpc44hSXO|YYm= MYeyNFAhdk1? NWruc4V1OTJiaB?= NGfVTZVFVVOR NV;MPYdETW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? M165WFI1QDB3OUS2
Trypanosoma brucei brucei NUTXXGtTTnWwY4Tpc44hSXO|YYm= M4HrV|IxOCCwTR?= NWmxUWU4OTJiaB?= MVzEUXNQ M1HB[mVn\mWldDDvckBxcG:|cHjheIllgWylaH;sbY5mKGyndnXs NV;m[YptOjR6MEW5OFY>
UM-UC-3 NFTMb45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\2VnRCUUN3ME2zNVUheE1? M3fuVnNCVkeHUh?=
SBC-1 MkfLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3zTWM2OD15NEKgdG0> M2f2OXNCVkeHUh?=
MKN1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUKzc4VHUUN3ME2yMlghdk1? MnvaV2FPT0WU
NCI-H720 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTNwNUegcm0> M4rOb3NCVkeHUh?=
BFTC-909 NVnydZpkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnpTWM2OD1|LkexJI5O M3PmPHNCVkeHUh?=
BPH-1 NEn6UJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzhe4RKSzVyPUSuO|Yhdk1? MonjV2FPT0WU
PC-3 MorMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTVwMEmgcm0> NX[zV45kW0GQR1XS
AN3-CA M4XkOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\sSINKUUN3ME21MlU3KG6P NF3kcGFUSU6JRWK=
HN NGCwUFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rGSWlEPTB;NT65OkBvVQ>? NYXJUWVlW0GQR1XS
HCC2218 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzDc|BsUUN3ME22MlYyKG6P MYXTRW5ITVJ?
KP-4 NXfLXWNyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfXTpdRUUN3ME23JI5O M1PI[3NCVkeHUh?=
LU-139 Ml7KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13rZ2lEPTB;Nz63O{BvVQ>? NXrQZ|c6W0GQR1XS
ETK-1 MmiyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU\Zflh1UUN3ME23Mlg5KG6P MoHtV2FPT0WU
Ramos-2G6-4C10 NITxVGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJR|UxRThwNEmgcm0> NUP4NlN4W0GQR1XS
MHH-PREB-1 NUjycoUyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXLTWM2OD17LkGyJI5O NGDwbIJUSU6JRWK=
DU-4475 MlviS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3vIWGlEPTB;OT60OEBvVQ>? MlTrV2FPT0WU
NCI-H1666 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLrcZRKSzVyPUmuO|Ehdk1? Mn7wV2FPT0WU
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MFE-280 M{CySWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\ydZhKSzVyPUmuPVkhdk1? NHTqZmlUSU6JRWK=
A549 MnXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{C4O2lEPTB;MUCuNVQhdk1? NGfKN21USU6JRWK=
769-P NHq3RYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPVWHJKSzVyPUGwMlQ1KG6P NUDSbWdqW0GQR1XS
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ES8 Ml75S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHTVToNKSzVyPUGwMlkhdk1? M4DkPHNCVkeHUh?=
PA-1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYXyOFhJUUN3ME2xNU45OiCwTR?= NITzNIVUSU6JRWK=
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HSC-3 M{HNcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrNWWdTUUN3ME2xNk4zOSCwTR?= MVnTRW5ITVJ?
H4 NFHlU3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7v[|RKSzVyPUGyMlY4KG6P NYS0Z5U3W0GQR1XS
BB65-RCC MkHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXjJR|UxRTF{LkeyJI5O M17NV3NCVkeHUh?=
NCI-H1793 NVzO[IRjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{TIcWlEPTB;MUKuPFIhdk1? M3:wcHNCVkeHUh?=
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GCT M1T3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13Gd2lEPTB;MUOuOlghdk1? NGLtdIlUSU6JRWK=
EoL-1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PaVGlEPTB;MUOuPVMhdk1? MYXTRW5ITVJ?
LB2241-RCC MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjYVWdKSzVyPUG0MlAyKG6P NGr0b|dUSU6JRWK=
ES5 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW\JR|UxRTF2Lke0JI5O MXjTRW5ITVJ?
LOXIMVI NU\IPIt2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUPJR|UxRTF2Lkm5JI5O NXXNNWNyW0GQR1XS
COR-L105 MlzUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXu5ZlRmUUN3ME2xOU4xPCCwTR?= NV;2UYR5W0GQR1XS
P12-ICHIKAWA NFzWbZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojxTWM2OD1zNT6xJI5O NGW2dZVUSU6JRWK=
CHL-1 M2C3RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTF3LkS1JI5O MljRV2FPT0WU
VMRC-RCZ NYX1dW46T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVTJR|UxRTF3Lk[zJI5O MoXXV2FPT0WU
HH NXmx[3FtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFzUeFRKSzVyPUG1Mlchdk1? MmThV2FPT0WU
NUGC-3 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTtTWM2OD1zNj6zOEBvVQ>? Ml;TV2FPT0WU
EGI-1 NInldmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXuWIdWUUN3ME2xOk41OyCwTR?= M4f2UHNCVkeHUh?=
OS-RC-2 MnHoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnsTWM2OD1zNj60O{BvVQ>? M1nLOHNCVkeHUh?=
MOLT-16 NVq5SXpVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{L5TmlEPTB;MUeuNVUhdk1? M1;JZ3NCVkeHUh?=
NCI-H209 NVjuRlIxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWDJR|UxRTF5LkK5JI5O MnW4V2FPT0WU
697 NF3WN|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTF5LkSzJI5O MVHTRW5ITVJ?
D-56MG MkLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnJNopXUUN3ME2xO{43QSCwTR?= MnHiV2FPT0WU
VA-ES-BJ MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTF5LkizJI5O MmL0V2FPT0WU
EW-16 MonaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\jTGhKSzVyPUG4MlA1KG6P MnLqV2FPT0WU
HGC-27 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFnWfnZKSzVyPUG4MlA3KG6P NFW1eHJUSU6JRWK=
ES7 M4Dn[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUGxN3JIUUN3ME2xPE4xQSCwTR?= MVPTRW5ITVJ?
HuH-7 NFjzTmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;2eWlEPTB;MUiuOEBvVQ>? M2n1fHNCVkeHUh?=
BCPAP M{HxWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTF6Lk[1JI5O Ml;MV2FPT0WU
SW1710 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFS1OmVKSzVyPUG4MlczKG6P NF7QcIFUSU6JRWK=
IST-MEL1 NUX2WXJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXJTWM2OD1zOD63O{BvVQ>? NYn1[HNpW0GQR1XS
SF295 M1\TSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzYVoJGUUN3ME2xPE46OyCwTR?= MUPTRW5ITVJ?
RPMI-7951 M1riRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\5RYVKSzVyPUG5MlI5KG6P NH3TW3pUSU6JRWK=
SF126 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTF7LkSxJI5O MVPTRW5ITVJ?
GAMG MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTF7LkS4JI5O NF;pXGZUSU6JRWK=
KNS-81-FD M2L4eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFm3emdKSzVyPUG5MlU1KG6P NEHWRXRUSU6JRWK=
RT-112 NXnrSVdyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrBR5l4UUN3ME2xPU43PiCwTR?= MVvTRW5ITVJ?
DEL MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfj[XpKSzVyPUKwMlQ6KG6P NYDmWIhGW0GQR1XS
CGTH-W-1 NX;zTZlHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH32cGJKSzVyPUKwMlY{KG6P MnrIV2FPT0WU
HOS NYTlNm55T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTJzLkC2JI5O MnvkV2FPT0WU
ES4 NVjRepI{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTJzLkC4JI5O Ml;VV2FPT0WU
RXF393 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYrXcmpyUUN3ME2yNU41PSCwTR?= Mmr2V2FPT0WU
NCI-H2030 MnX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PZSmlEPTB;MkGuOVIhdk1? M2f4T3NCVkeHUh?=
YH-13 NX7sOll5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\Ib2FKSzVyPUKxMlg5KG6P NV;2NXhoW0GQR1XS
HT-1080 NHfFVHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHL3SHVKSzVyPUKxMlk{KG6P M1L2[nNCVkeHUh?=
NCI-SNU-1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEXMSnhKSzVyPUKxMlk2KG6P NUXuUlFDW0GQR1XS
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786-0 NWLqR2tVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWWwWFR5UUN3ME2yNk4zQSCwTR?= M1[wWXNCVkeHUh?=
ME-180 NXW1UG1JT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnjTWM2OD1{Mj60N{BvVQ>? MnO2V2FPT0WU
NB69 M{LrOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPFPWVKSzVyPUKyMlU{KG6P MkjqV2FPT0WU
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TGBC1TKB MlfHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13Hc2lEPTB;MkOuNFUhdk1? NEO5copUSU6JRWK=
SW780 NHLjTnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PpUWlEPTB;MkOuNVMhdk1? NYK1dnZHW0GQR1XS
MG-63 M4PsW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TVNmlEPTB;MkOuOFUhdk1? NEK2U2pUSU6JRWK=
BV-173 MluxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVX3TpZmUUN3ME2yN{45PyCwTR?= NF24b2NUSU6JRWK=
CAL-51 NV;nW2dHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2W5T2lEPTB;MkOuPFkhdk1? MVvTRW5ITVJ?
A375 NGrybopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn\1TWM2OD1{Mz65N{BvVQ>? MWnTRW5ITVJ?
MEL-HO MlTqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTLUZJzUUN3ME2yOE4xPCCwTR?= NIHSPG9USU6JRWK=
EFO-27 M{Cy[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;YNYtnUUN3ME2yOE4{OyCwTR?= NInHOHlUSU6JRWK=
Hs-578-T MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTPfJlKSzVyPUK0MlU5KG6P MlvOV2FPT0WU
NBsusSR MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTm[JlKSzVyPUK0MlYhdk1? MorBV2FPT0WU
CTB-1 M164c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHfKfYpKSzVyPUK0MlY4KG6P M1HFXXNCVkeHUh?=
FTC-133 M4LVZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTUTWM2OD1{NT6xJI5O M{e4S3NCVkeHUh?=
MOLT-4 NEDMNYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEKyNnhKSzVyPUK1MlEzKG6P M{HrOHNCVkeHUh?=
HO-1-N-1 NV62cFVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnjMTWM2OD1{NT6xOUBvVQ>? NGrMNHFUSU6JRWK=
ES3 NVHyO|FqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTJ3LkKyJI5O NUfwPXpvW0GQR1XS
TI-73 MkDwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXpZZpKSzVyPUK1MlI5KG6P M3fj[XNCVkeHUh?=
MPP-89 NEjiOoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvrTFloUUN3ME2yOU4{OiCwTR?= M3\wbnNCVkeHUh?=
KYSE-150 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;kNFVKSzVyPUK1Mlg6KG6P NVjWN3puW0GQR1XS
LXF-289 NGDOemxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjZVYNKSzVyPUK2MlA1KG6P NFG0R|dUSU6JRWK=
SK-LU-1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M321cWlEPTB;Mk[uNVchdk1? M3iwT3NCVkeHUh?=
HOP-92 M{TZXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHITWM2OD1{Nj60PEBvVQ>? NVzS[2RrW0GQR1XS
HuO9 NILSNI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTJ4Lke2JI5O MlLrV2FPT0WU
SW962 NG\Fe4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELNNpZKSzVyPUK2Mlc3KG6P NYXrSGFoW0GQR1XS
RS4-11 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXrhbW81UUN3ME2yOk46OSCwTR?= NF\tR4NUSU6JRWK=
NCI-H292 Mn7hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jveWlEPTB;Mkegcm0> MVrTRW5ITVJ?
DB MlvaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\1TGlEPTB;MkeuN|Yhdk1? NFjOe5dUSU6JRWK=
SW1088 NGDibY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHkRYhKSzVyPUK4MlI6KG6P NWCxSnJTW0GQR1XS
A204 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTJ6LkS3JI5O M4rzSHNCVkeHUh?=
A3-KAW NIXQPZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvvblFlUUN3ME2yPE43PCCwTR?= NXX5eo1jW0GQR1XS
MV-4-11 Ml7SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWPJR|UxRTJ6Lkegcm0> M1nlfXNCVkeHUh?=
ES1 NI\PbHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfuUWZTUUN3ME2yPE45PCCwTR?= M1KyWHNCVkeHUh?=
ONS-76 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\FZmlEPTB;MkmuNFUhdk1? MX\TRW5ITVJ?
D-263MG NXTKV20xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPseJBKSzVyPUK5MlM2KG6P M4XmfnNCVkeHUh?=
U-2-OS NIS5XHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\uTWM2OD1{OT61JI5O NF[2R4ZUSU6JRWK=
T98G MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\H[JRCUUN3ME2yPU45QCCwTR?= NGPaeJhUSU6JRWK=
GI-ME-N NI[3b4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXPJR|UxRTJ7LkmxJI5O MWHTRW5ITVJ?
BHT-101 NIfCTWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTNyLkC1JI5O M1HYSnNCVkeHUh?=
NOS-1 NYXxcFE4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTNyLkGyJI5O M4rw[HNCVkeHUh?=
AsPC-1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDCTWM2OD1|MD6yJI5O NXL3cpdnW0GQR1XS
QIMR-WIL Mkn0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\ibY01UUN3ME2zNE43KG6P MXLTRW5ITVJ?
JVM-3 NFP4eFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vlZmlEPTB;M{CuPFMhdk1? M2SzT3NCVkeHUh?=
KU-19-19 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnn6TWM2OD1|MT6xN{BvVQ>? M2Wz[3NCVkeHUh?=
OVCAR-8 NUXj[49RT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzQTWM2OD1|MT6yOkBvVQ>? NX3CTW9RW0GQR1XS
BEN NX31NHd[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknwTWM2OD1|MT62N{BvVQ>? NXHpRohCW0GQR1XS
BE-13 NXm4doduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfMboJKSzVyPUOxMlgzKG6P MVTTRW5ITVJ?
EW-18 NXGy[|RQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfPSo1xUUN3ME2zNU45PiCwTR?= MX;TRW5ITVJ?
ECC10 NUS0b29ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTNzLkm1JI5O MlHXV2FPT0WU
CTV-1 NXuySld2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfVR2Y6UUN3ME2zNk45OiCwTR?= MWTTRW5ITVJ?
COLO-800 MnvVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm\QTWM2OD1|Mj65NkBvVQ>? NHHDT5JUSU6JRWK=
A2058 NEfaZZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfF[XpqUUN3ME2zN{4zPSCwTR?= MnTzV2FPT0WU
VM-CUB-1 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYjjV25pUUN3ME2zN{41OyCwTR?= NHKzb5NUSU6JRWK=
Ca9-22 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGPRfZRKSzVyPUOzMlU2KG6P MnKwV2FPT0WU
COLO-684 NITmV25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTN|LkW4JI5O MYXTRW5ITVJ?
RPMI-8226 Mk\1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPOTWM2OD1|Mz64NkBvVQ>? NX3NRot5W0GQR1XS
SK-NEP-1 NYXDPYUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFjwZnNKSzVyPUO0MlE2KG6P MX3TRW5ITVJ?
Becker NIjV[VNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFqyT2ZKSzVyPUO0MlIyKG6P MnTGV2FPT0WU
NCI-H28 MnjjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PYeWlEPTB;M{SuOFQhdk1? NF23cHFUSU6JRWK=
CAL-120 NF\MV4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\2XWlEPTB;M{SuO|Ihdk1? M3[5dXNCVkeHUh?=
MDA-MB-157 MlLVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1jxOGlEPTB;M{WuOFEhdk1? MV\TRW5ITVJ?
OVCAR-5 NVzGeZc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFKzcnNKSzVyPUO1MlQ4KG6P MYTTRW5ITVJ?
LAMA-84 MlrNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XQbmlEPTB;M{WuPFchdk1? NHTSdVFUSU6JRWK=
CAKI-1 NWm5dFB3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTN4LkSzJI5O NX3yTXFiW0GQR1XS
Daoy MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfMNZR2UUN3ME2zOk44KG6P MXXTRW5ITVJ?
CAL-62 NEPUeWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nme2lEPTB;M{[uPFYhdk1? M3rnNnNCVkeHUh?=
8-MG-BA NITUVHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrtXGRzUUN3ME2zO{4zPSCwTR?= M{jmT3NCVkeHUh?=
8505C MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnP6TWM2OD1|Nz61NUBvVQ>? MYTTRW5ITVJ?
LNCaP-Clone-FGC NYLBcHdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTN5LkW5JI5O NIm0S|ZUSU6JRWK=
CAL-39 NEHZS4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTBTWM2OD1|Nz65JI5O MYXTRW5ITVJ?
MN-60 NW[5bYFFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTN5Lkm2JI5O MXLTRW5ITVJ?
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HCC1419 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPkW4Z1UUN3ME2zPE44OSCwTR?= NV7WS5I1W0GQR1XS
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HD-MY-Z MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmH3TWM2OD12ND65NkBvVQ>? MVjTRW5ITVJ?
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NCI-H2405 NIe2VVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M33id2lEPTB;NUSuPFghdk1? MnHEV2FPT0WU
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HAL-01 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmC2TWM2OD13NT64N{BvVQ>? NHvofYtUSU6JRWK=
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PANC-08-13 MmTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\WSWlEPTB;NUiuNFEhdk1? M2rleHNCVkeHUh?=
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LN-405 M{jCOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4[4XGlEPTB;NkOuPFUhdk1? M1;CV3NCVkeHUh?=
NCI-H1581 MnHUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm[yTWM2OD14ND6wN{BvVQ>? MXnTRW5ITVJ?
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KU812 NVTKcmJWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHtTWM2OD14OD62PUBvVQ>? M1PifnNCVkeHUh?=
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KOSC-2 NWG0OHZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn3uTWM2OD14OT65O{BvVQ>? NIP3[IxUSU6JRWK=
MC-IXC MlvDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLac5hFUUN3ME23NE4xQCCwTR?= MnK2V2FPT0WU
SCC-4 NVOxPIRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLoXW9{UUN3ME23NU4{QCCwTR?= Mn22V2FPT0WU
Calu-3 Moj2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrlTI1rUUN3ME23NU46QCCwTR?= MU\TRW5ITVJ?
RPMI-8866 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DXNWlEPTB;N{KuPFIhdk1? Ml7EV2FPT0WU
OVCAR-4 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDoTWM2OD15Mz6zOkBvVQ>? MYfTRW5ITVJ?
OAW-42 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4f5TmlEPTB;N{OuN|khdk1? MWTTRW5ITVJ?
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PANC-03-27 MoflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTd4LkK1JI5O MkX4V2FPT0WU
S-117 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTPTWM2OD15Nj6yO{BvVQ>? M{f0cXNCVkeHUh?=
SK-MEL-2 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmXpTWM2OD15Nj63OUBvVQ>? NXHNUWlmW0GQR1XS
LK-2 NVjCdWNyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHrNppzUUN3ME23O{4xPSCwTR?= M1HoU3NCVkeHUh?=
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LU-134-A Ml:xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NED1WYpKSzVyPUe5MlA{KG6P NV\oWI1oW0GQR1XS
5637 Mn:yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPTTFFKSzVyPUe5MlI{KG6P MY\TRW5ITVJ?
NCI-H1437 MofPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\LTWM2OD16MD61JI5O NIriWpFUSU6JRWK=
NCI-H460 NWfqd49GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;WfFJnUUN3ME24NU4zOyCwTR?= NGHldFNUSU6JRWK=
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COLO-678 M1HuSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHuOolDUUN3ME2yMlg{PzZ6IN88US=> NFzHRWpUSU6JRWK=
SK-N-DZ MnHTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI[xOGlKSzVyPUKuPFY{QDFizszN M{TSRXNCVkeHUh?=
NCI-H82 NVXTS3h4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHuXVY3UUN3ME2yMlkxOzZ7IN88US=> NH;1eVVUSU6JRWK=
JVM-2 MlHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XTbGlEPTB;Mz6wN|E5QCEQvF2= NHnrbmZUSU6JRWK=
SW1116 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTNwMEW0NVEh|ryP M2XJcHNCVkeHUh?=
MDA-MB-453 NYLzenJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmnlTWM2OD1|LkGwOFM6KM7:TR?= MXjTRW5ITVJ?
Calu-6 NVjOVJJjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY[4[|FxUUN3ME2zMlE6QTdizszN NFHGcolUSU6JRWK=
SHP-77 M{jTcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj3TWM2OD1|LkWyPEDPxE1? NYTNc3VFW0GQR1XS
Capan-2 NXvYNo5XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjSbGlGUUN3ME20MlMzPThzIN88US=> NFLHW3dUSU6JRWK=
SW948 NIqxOWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml3HTWM2OD12Lke0O|c6KM7:TR?= MWHTRW5ITVJ?
HDLM-2 M1zIWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTveVlIUUN3ME21MlA4PzJ3IN88US=> MXrTRW5ITVJ?
LAN-6 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TvR2lEPTB;Nj6yNVQ6PSEQvF2= M3jZTnNCVkeHUh?=
LU-135 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTEemJjUUN3ME22MlQ{ODd5IN88US=> NXz0eVFoW0GQR1XS
T84 M3zWd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHL6WHBKSzVyPU[uPVg3PCEQvF2= M3TsdHNCVkeHUh?=
CAPAN-1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFP5c25KSzVyPUeuOlIzOzNizszN NWLTcpMzW0GQR1XS
SW1417 MnX3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRTdwOUG3N|Eh|ryP NIn1NHdUSU6JRWK=
BALL-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRThwNUC0NFkh|ryP NF22V|JUSU6JRWK=
HT-29 M3fiSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH33TW9KSzVyPUmuNFc2QTlizszN MW\TRW5ITVJ?
C3A M2TPWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTlwOEizPVQh|ryP MVrTRW5ITVJ?
NCI-H1993 NYruPG5lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmr0TWM2OD1zMD61NFgyKM7:TR?= NYPGR3FTW0GQR1XS
SK-MEL-1 NWHwboRnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTFzLk[yPFkh|ryP MY\TRW5ITVJ?
DU-145 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLjTFExUUN3ME2xOE42ODV{IN88US=> NGX4eYlUSU6JRWK=
KP-N-YN M4fke2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVjMZXhlUUN3ME2xOE42OTB|IN88US=> NILJO4lUSU6JRWK=
CCRF-CEM NWDIO2ZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTF2Lke4NFkh|ryP NYnZeolCW0GQR1XS
ZR-75-30 NEXyXlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmeyTWM2OD1zNj6zN|A{KM7:TR?= NX3RWlhNW0GQR1XS
A673 M3fIW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NISwN|VKSzVyPUKwMlU2ODdizszN NWPZVHYyW0GQR1XS
K-562 MkTXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH35bIlKSzVyPUK4MlQyQDNizszN NVXCWYUxW0GQR1XS

... Click to View More Cell Line Experimental Data

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

Protocol

Kinase Assay:

[1]

+ Expand

In vitro Protein Kinase, PI3K, and mTOR Assays:

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

[2]

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

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


    (Only for Reference)
Animal Research:

[1]

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

Solubility (25°C)

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

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

Chemical Information

Molecular Weight 469.55
Formula

C30H23N5O

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

Bio Calculators

Molarity Calculator

Molarity Calculator

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

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

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

Dilution Calculator

Dilution Calculator

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

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

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

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

The Serial Dilution Calculator Equation

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Molecular Weight Calculator

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

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

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

Tech Support

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

Handling Instructions

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

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

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

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

  • Answer:

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

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID