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 MnrPRY51cW2rY4LvZolidCCDc4PhfS=> MoXUNVghcA>? MWTEUXNQ NXHBOWFqSW62aYTyfZBidm:|b33hcEBi[3Srdnn0fUB4cXSqIFXDOVAhd2ZiMD6wNFI2KM7:TR?= MYGyOFgxPTl2Nh?=
MCF7 NVP4RoN3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1HrO|AvODFvMUCwJO69VQ>? MVW0PEBp MkXiSG1UVw>? NF:xNJlKSzVyPUCuO|Mh|ryP NVXGcZE3OjN6N{G5NFQ>
HCT116 M4LIZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWCwMlAyNTFyMDFOwG0> M{PJUlQ5KGh? MofOSG1UVw>? MnvXTWM2OD1zLkG2JO69VQ>? MUGyN|g4OTlyNB?=
U87MG MmO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonFNE4xOS1zMECg{txO NHP3elE1QCCq NX;TZ5ZETE2VTx?= MV\JR|UxRTFwM{Kg{txO MYiyN|g4OTlyNB?=
HBC4 NXrpfYJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWjxWJlwOC5yMT2xNFAh|ryP M1;XRVQ5KGh? MlXDUI9oKEeLNUC9MVgvPjFiTR?= MYGyNlM{PjJ2Nh?=
BSY1 NHHqVXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF61cFExNjBzLUGwNEDPxE1? MlLwOFghcA>? M4LzdGxw\yCJSUWwQU05NjR6IF2= NVmxdG9jOjJ|M{[yOFY>
HBC5 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHzvdmUxNjBzLUGwNEDPxE1? MkXGOFghcA>? M4PXRWxw\yCJSUWwQU04Njh5IF2= MVGyNlM{PjJ2Nh?=
MCF7 NGG4O|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWm5fog5OC5yMT2xNFAh|ryP MmS1OFghcA>? MmK0UI9oKEeLNUC9MVgvOTZiTR?= MVeyNlM{PjJ2Nh?=
MDA-MB-231 M1XQfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGqzNGkxNjBzLUGwNEDPxE1? MWK0PEBp MVjMc4chT0l3ME2tPE4xQSCP MkX0NlI{OzZ{NE[=
U251 NXHDU2J2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHhe|UxNjBzLUGwNEDPxE1? NFPJU2U1QCCq NUXEPIllVG:pIFfJOVA:NTdwNk[gUS=> NH\VTYQzOjN|NkK0Oi=>
SF268 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYSwMlAyNTFyMDFOwG0> MWG0PEBp NXHMUnRlVG:pIFfJOVA:NTdwOUKgUS=> M4e2SlIzOzN4MkS2
SF295 NYHSOZA6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknUNE4xOS1zMECg{txO MlPLOFghcA>? M{jBS2xw\yCJSUWwQU05NjNzIF2= Ml7NNlI{OzZ{NE[=
SF539 NES0Tm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFS0WpUxNjBzLUGwNEDPxE1? NF7Nb|U1QCCq MXnMc4chT0l3ME2tPE42QSCP MUWyNlM{PjJ2Nh?=
SNB75 Mlv6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHuNE4xOS1zMECg{txO M4Pa[|Q5KGh? MVnMc4chT0l3ME2tPE42QCCP MWiyNlM{PjJ2Nh?=
SNB78 M{nic2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1KweFAvODFvMUCwJO69VQ>? M4jCPVQ5KGh? M4HMcWxw\yCJSUWwQU05NjZ3IF2= MY[yNlM{PjJ2Nh?=
HCC2998 M{[1S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PBWFAvODFvMUCwJO69VQ>? MVS0PEBp M3LIemxw\yCJSUWwQU05NjB3IF2= NXnBPWJnOjJ|M{[yOFY>
KM12 M3X4O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;4[|AvODFvMUCwJO69VQ>? NEnmNmY1QCCq NWjjdW9RVG:pIFfJOVA:NTdwNUSgUS=> M{PrWFIzOzN4MkS2
HT-29 Mn;6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnYNE4xOS1zMECg{txO NGPxRXI1QCCq NHfJbGdNd2diR1m1NF0uPy55NTDN MV[yNlM{PjJ2Nh?=
HCT15 NXTXTYdYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7VNXZxOC5yMT2xNFAh|ryP NILPTnc1QCCq M2HZZmxw\yCJSUWwQU05NjB|IF2= NYnUdXFZOjJ|M{[yOFY>
HCT116 MoPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fWUFAvODFvMUCwJO69VQ>? M2qybVQ5KGh? M1zCV2xw\yCJSUWwQU04NjZzIF2= NE\6VVczOjN|NkK0Oi=>
NCI-H23 NYizbZloT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXqwMlAyNTFyMDFOwG0> NXLZeZpUPDhiaB?= M4WyNGxw\yCJSUWwQU04NjZ2IF2= M1K4OlIzOzN4MkS2
NCI-H226 M2\kW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\zPYYxNjBzLUGwNEDPxE1? NGjNT4o1QCCq NX\4bHVuVG:pIFfJOVA:NThwNESgUS=> NXPvPXJMOjJ|M{[yOFY>
NCI-H522 MmTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFftVJMxNjBzLUGwNEDPxE1? MV:0PEBp MXHMc4chT0l3ME2tPE41PSCP M4TVPFIzOzN4MkS2
NCI-H438 MojxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLLemExNjBzLUGwNEDPxE1? MVi0PEBp NYDyOmZjVG:pIFfJOVA:NThwMUGgUS=> NI\reFAzOjN|NkK0Oi=>
A549 Ml7aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrCVm9xOC5yMT2xNFAh|ryP M{P0blQ5KGh? MX7Mc4chT0l3ME2tPE4xPyCP NVP0UnVJOjJ|M{[yOFY>
DMS273 MkHQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLoNE4xOS1zMECg{txO MorIOFghcA>? NHz0eoJNd2diR1m1NF0uPy56MDDN NXr4NItuOjJ|M{[yOFY>
DMS114 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\jcmZrOC5yMT2xNFAh|ryP MUG0PEBp NE[1ZpBNd2diR1m1NF0uQC5|OTDN NHLWNG0zOjN|NkK0Oi=>
LOXIMVI Ml;QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm[xNE4xOS1zMECg{txO NXX3fGJ2PDhiaB?= MWrMc4chT0l3ME2tPE43PiCP M3Lz[FIzOzN4MkS2
OVCAR3 NHe0dGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MorkNE4xOS1zMECg{txO MX60PEBp M{jDWWxw\yCJSUWwQU05NjF5IF2= MV[yNlM{PjJ2Nh?=
OVCAR4 NUjSN3F5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVmwMlAyNTFyMDFOwG0> Mk\GOFghcA>? NH3zeHRNd2diR1m1NF0uQC53ODDN NHH1dFUzOjN|NkK0Oi=>
OVCAR5 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVHIVVNWOC5yMT2xNFAh|ryP NVq1OVdrPDhiaB?= NV6wbmdVVG:pIFfJOVA:NTdwNUegUS=> NXzuUIZtOjJ|M{[yOFY>
OVCAR8 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7ZfVcxNjBzLUGwNEDPxE1? MkW1OFghcA>? NGDlVpFNd2diR1m1NF0uPy56NDDN M4XUcVIzOzN4MkS2
SKOV3 M3XUU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDaPY0xNjBzLUGwNEDPxE1? MV[0PEBp MkXVUI9oKEeLNUC9MVgvPDFiTR?= NGHrb4czOjN|NkK0Oi=>
RXF631L NYrOfZY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjnS5ExNjBzLUGwNEDPxE1? MWG0PEBp MmjJUI9oKEeLNUC9MVgvOjFiTR?= NVK1WWpOOjJ|M{[yOFY>
ACHN MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M33BTVAvODFvMUCwJO69VQ>? M3rLXFQ5KGh? MUXMc4chT0l3ME2tO{46PSCP Mln6NlI{OzZ{NE[=
St-4 NH76SI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrDTGZwOC5yMT2xNFAh|ryP NFXSW4I1QCCq NX\GWGFDVG:pIFfJOVA:NTdwNEegUS=> MXqyNlM{PjJ2Nh?=
MKN1 NHjkS4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvKNE4xOS1zMECg{txO MVi0PEBp MYLMc4chT0l3ME2tPE41OSCP MVOyNlM{PjJ2Nh?=
MKN7 NEDj[YpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PX[FAvODFvMUCwJO69VQ>? M1jWWFQ5KGh? MX3Mc4chT0l3ME2tO{43QCCP NInLVXYzOjN|NkK0Oi=>
MKN28 NEfoO49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV71XGZsOC5yMT2xNFAh|ryP NITrVGE1QCCq M1[yd2xw\yCJSUWwQU04NjB5IF2= MWKyNlM{PjJ2Nh?=
MKN45 MoWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonwNE4xOS1zMECg{txO NVzyeXZQPDhiaB?= MUXMc4chT0l3ME2tPE4{PCCP NYSxWYU1OjJ|M{[yOFY>
MKN74 NEDHdYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\0NoxjOC5yMT2xNFAh|ryP MXS0PEBp NUnIPJJKVG:pIFfJOVA:NTdwNEKgUS=> NWLMRY5NOjJ|M{[yOFY>
DU145 MoGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlGyNE4xOS1zMECg{txO NU\hUpBQPDhiaB?= MXHMc4chT0l3ME2tPE4yPiCP M2Loc|IzOzN4MkS2
PC3 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW[wMlAyNTFyMDFOwG0> MnLjOFghcA>? MmLZUI9oKEeLNUC9MVgvPjZiTR?= MlnjNlI{OzZ{NE[=
Trypanosoma brucei brucei Ml7YSpVv[3Srb36gRZN{[Xl? MVmyNFAhdk1? NFzqc|kyOiCq MlTpSG1UVw>? MXzE[YNz\WG|ZTDpckBxcG:|cHjveIllgWxiaX7vd4l1d2xicHjvd5Bp[XSnIHzleoVt M2rXbFI1QDB3OUS2
Trypanosoma brucei brucei M3\yfGZ2dmO2aX;uJGF{e2G7 MXuxPEBp NW\oV3R2TE2VTx?= NXKxd2VCUW6qaXLpeIlwdiCxZjDy[YNmeHSxcj3t[YRq[XSnZDDlcoRw[3m2b4Ppd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjD0doFve2[ncoLpckB2eHSja3W= NEjZWHIzPDhyNUm0Oi=>
Trypanosoma brucei brucei MXPGeY5kfGmxbjDBd5NigQ>? NGfDfYgzODBibl2= NHXI[XcyOiCq NIjKWnRFVVOR MmO0SYZn\WO2IH;uJJNxcGmwZ3;tfYxmcW5ibHX2[Yw> M{jrVVI1QDB3OUS2
Trypanosoma brucei brucei NYLPfZpXTnWwY4Tpc44hSXO|YYm= M{nVOlIxOCCwTR?= MUSxNkBp MlTKSG1UVw>? M1O3dGVn\mWldDDvckBxcG:|cHjheIllgWylaH;sbY5mKGyndnXs MlfWNlQ5ODV7NE[=
UM-UC-3 MmP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPEXYkxUUN3ME2zNVUheE1? NHjTdJVUSU6JRWK=
SBC-1 M2jDUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTd2MjDwUS=> M1jpUXNCVkeHUh?=
MKN1 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTJwODDuUS=> MVfTRW5ITVJ?
NCI-H720 M2XzVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVzJR|UxRTNwNUegcm0> NIfBcItUSU6JRWK=
BFTC-909 NEDiXpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3sW|ZKSzVyPUOuO|Ehdk1? MlniV2FPT0WU
BPH-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIqyNGZKSzVyPUSuO|Yhdk1? NHrW[JlUSU6JRWK=
PC-3 NHPnW2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;Ve2lEPTB;NT6wPUBvVQ>? NYDWeVVOW0GQR1XS
AN3-CA M3HQVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvhNXdzUUN3ME21MlU3KG6P M4XXS3NCVkeHUh?=
HN MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkT2TWM2OD13Lkm2JI5O NV\yR5ZEW0GQR1XS
HCC2218 NVfsTYlMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHKXJRKSzVyPU[uOlEhdk1? MkjyV2FPT0WU
KP-4 MnTMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\XSGRGUUN3ME23JI5O NXXOdYw1W0GQR1XS
LU-139 M2jyfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLMUogzUUN3ME23Mlc4KG6P NFSzSmhUSU6JRWK=
ETK-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnOwTWM2OD15Lki4JI5O MVPTRW5ITVJ?
Ramos-2G6-4C10 NVrlOW92T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3r4TWlEPTB;OD60PUBvVQ>? MXrTRW5ITVJ?
MHH-PREB-1 NWjCPXlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTlwMUKgcm0> NVG0eFJYW0GQR1XS
DU-4475 Ml;ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;pUHlDUUN3ME25MlQ1KG6P NFfOOXpUSU6JRWK=
NCI-H1666 NHruPYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPyTWM2OD17LkexJI5O NHvuOYhUSU6JRWK=
CAMA-1 M4[0NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4OwTWlEPTB;OT64JI5O NUD5eldjW0GQR1XS
TYK-nu MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXP0b|J2UUN3ME25Mlk1KG6P M{LN[XNCVkeHUh?=
MFE-280 NFP2fVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTlwOUmgcm0> NULSbJBEW0GQR1XS
A549 MmThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTJTWM2OD1zMD6xOEBvVQ>? MVjTRW5ITVJ?
769-P M2L6S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmD6TWM2OD1zMD60OEBvVQ>? MVrTRW5ITVJ?
L-363 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEe4OY5KSzVyPUGwMlY6KG6P Mn3YV2FPT0WU
ES8 MkXaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTD[G9VUUN3ME2xNE46KG6P M{\VOHNCVkeHUh?=
PA-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTFzLkiyJI5O MYXTRW5ITVJ?
Mewo NF[5blBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTFzLkm5JI5O MUfTRW5ITVJ?
HSC-3 M{WzVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLGfoxLUUN3ME2xNk4zOSCwTR?= NH3kWVRUSU6JRWK=
H4 NVrPd4tVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFKxeFRKSzVyPUGyMlY4KG6P MoTTV2FPT0WU
BB65-RCC MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTF{LkeyJI5O NF\K[JJUSU6JRWK=
NCI-H1793 NXXZU41zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTF{LkiyJI5O MnfPV2FPT0WU
KARPAS-45 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4T2TGlEPTB;MUOuOVEhdk1? NWC4SHhyW0GQR1XS
GCT M2nBWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HuO2lEPTB;MUOuOlghdk1? MXjTRW5ITVJ?
EoL-1 Mn3PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;TPWtxUUN3ME2xN{46OyCwTR?= MnfSV2FPT0WU
LB2241-RCC NX\EXWNQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vScGlEPTB;MUSuNFEhdk1? Mo\ZV2FPT0WU
ES5 NXnoTYdRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXnV4psUUN3ME2xOE44PCCwTR?= NHG2empUSU6JRWK=
LOXIMVI NVjZWFA3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIrUPFRKSzVyPUG0Mlk6KG6P M1q4THNCVkeHUh?=
COR-L105 NEPGbXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLSVmVmUUN3ME2xOU4xPCCwTR?= M1X0ZXNCVkeHUh?=
P12-ICHIKAWA MojiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYX1NJI5UUN3ME2xOU4yKG6P M1KxcXNCVkeHUh?=
CHL-1 NIXQ[JlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFT4UVNKSzVyPUG1MlQ2KG6P MlSzV2FPT0WU
VMRC-RCZ NX3nTHFWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTF3Lk[zJI5O MVPTRW5ITVJ?
HH Mn3US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH6wU3ZKSzVyPUG1Mlchdk1? NWnYem5uW0GQR1XS
NUGC-3 M3;RU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\QSppvUUN3ME2xOk4{PCCwTR?= NYrUXIp{W0GQR1XS
EGI-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTF4LkSzJI5O NE\uUlJUSU6JRWK=
OS-RC-2 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTF4LkS3JI5O NGHTdlJUSU6JRWK=
MOLT-16 NInpb4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmXPTWM2OD1zNz6xOUBvVQ>? MojMV2FPT0WU
NCI-H209 MmDBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTF5LkK5JI5O MmjmV2FPT0WU
697 NGXkVoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjhTGRKSzVyPUG3MlQ{KG6P M4HlRXNCVkeHUh?=
D-56MG NYS5To04T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvzNYQ4UUN3ME2xO{43QSCwTR?= Mn3VV2FPT0WU
VA-ES-BJ NVXxblZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\pXGRwUUN3ME2xO{45OyCwTR?= M3njbXNCVkeHUh?=
EW-16 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\ZeodKSzVyPUG4MlA1KG6P M{K3RnNCVkeHUh?=
HGC-27 NV\YcolHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHSy[ZFKSzVyPUG4MlA3KG6P NYPKU4hpW0GQR1XS
ES7 M2PrVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\aVFBKSzVyPUG4MlA6KG6P NWfrc29zW0GQR1XS
HuH-7 M2HGSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmi0TWM2OD1zOD60JI5O MVvTRW5ITVJ?
BCPAP M3nwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTF6Lk[1JI5O NVPuTVhqW0GQR1XS
SW1710 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;hOG1LUUN3ME2xPE44OiCwTR?= M{fyXXNCVkeHUh?=
IST-MEL1 MlPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVLhWFEyUUN3ME2xPE44PyCwTR?= Mn65V2FPT0WU
SF295 NFPlW3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTF6LkmzJI5O M3HLc3NCVkeHUh?=
RPMI-7951 NWnndFRvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXHJR|UxRTF7LkK4JI5O M4\BOXNCVkeHUh?=
SF126 NYjZbINzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTF7LkSxJI5O MW\TRW5ITVJ?
GAMG MnLES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTF7LkS4JI5O M{DKXXNCVkeHUh?=
KNS-81-FD NYi1fIhGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1j5e2lEPTB;MUmuOVQhdk1? NVnnUJRFW0GQR1XS
RT-112 MnHzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M172XGlEPTB;MUmuOlYhdk1? NHXBUIZUSU6JRWK=
DEL NEPsU|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWC5PHd3UUN3ME2yNE41QSCwTR?= NHXV[HBUSU6JRWK=
CGTH-W-1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HGSWlEPTB;MkCuOlMhdk1? MlnRV2FPT0WU
HOS MoX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTJzLkC2JI5O NYHod2NiW0GQR1XS
ES4 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnxNGFKSzVyPUKxMlA5KG6P NYrUV2FPW0GQR1XS
RXF393 NFjCdplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\p[2JKSzVyPUKxMlQ2KG6P MlywV2FPT0WU
NCI-H2030 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LLW2lEPTB;MkGuOVIhdk1? NF\zO4FUSU6JRWK=
YH-13 NUDO[3JMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfxTWM2OD1{MT64PEBvVQ>? M1fjWHNCVkeHUh?=
HT-1080 NXKwUosyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTJzLkmzJI5O NF\aOJhUSU6JRWK=
NCI-SNU-1 MlfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTJzLkm1JI5O M1;FPXNCVkeHUh?=
G-402 M1PPNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnPiTWM2OD1{Mj6xOkBvVQ>? NGPhO|FUSU6JRWK=
786-0 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTJTWM2OD1{Mj6yPUBvVQ>? MUHTRW5ITVJ?
ME-180 Ml\iS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTJ{LkSzJI5O M1XFdXNCVkeHUh?=
NB69 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\jUmtqUUN3ME2yNk42OyCwTR?= M{WyO3NCVkeHUh?=
J-RT3-T3-5 M3rNcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2f0XWlEPTB;MkKuPVYhdk1? NGf3WXNUSU6JRWK=
TGBC1TKB MkDMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoHSTWM2OD1{Mz6wOUBvVQ>? MVTTRW5ITVJ?
SW780 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTJ|LkGzJI5O NHO1WnJUSU6JRWK=
MG-63 MlPxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHTLcGxKSzVyPUKzMlQ2KG6P NHrwV3NUSU6JRWK=
BV-173 Mme2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmroTWM2OD1{Mz64O{BvVQ>? MVvTRW5ITVJ?
CAL-51 NYrJeXVKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PESmlEPTB;MkOuPFkhdk1? Ml34V2FPT0WU
A375 MkDCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HPNmlEPTB;MkOuPVMhdk1? MYLTRW5ITVJ?
MEL-HO NIrCbnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvORmx[UUN3ME2yOE4xPCCwTR?= Moe2V2FPT0WU
EFO-27 MoDoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTmTWM2OD1{ND6zN{BvVQ>? Mo\VV2FPT0WU
Hs-578-T NGK4VGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnxTWM2OD1{ND61PEBvVQ>? NXnkSo1oW0GQR1XS
NBsusSR NFG2Z3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPXTWM2OD1{ND62JI5O M1i3TnNCVkeHUh?=
CTB-1 NFTER3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnyZVNKSzVyPUK0MlY4KG6P M3XESXNCVkeHUh?=
FTC-133 NVfV[Xl[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfyfYFKSzVyPUK1MlEhdk1? NFrCd3pUSU6JRWK=
MOLT-4 NH3SO5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUfJR|UxRTJ3LkGyJI5O M1rGUHNCVkeHUh?=
HO-1-N-1 NVLodpNRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYrzRWwyUUN3ME2yOU4yPSCwTR?= MU\TRW5ITVJ?
ES3 NXSwVWtFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MniyTWM2OD1{NT6yNkBvVQ>? MmTmV2FPT0WU
TI-73 MnvkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7JTWM2OD1{NT6yPEBvVQ>? MnPxV2FPT0WU
MPP-89 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonXTWM2OD1{NT6zNkBvVQ>? NG\lUmZUSU6JRWK=
KYSE-150 NFzzXIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTJ3Lki5JI5O MXPTRW5ITVJ?
LXF-289 NFK5RlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnxXmRLUUN3ME2yOk4xPCCwTR?= MoTUV2FPT0WU
SK-LU-1 NV3CeVRRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2npcmlEPTB;Mk[uNVchdk1? MorrV2FPT0WU
HOP-92 NVr3WHV7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPG[ZFKSzVyPUK2MlQ5KG6P M3qwU3NCVkeHUh?=
HuO9 NUThSll7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTJ4Lke2JI5O NV;vZZd4W0GQR1XS
SW962 M{LWb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTsW2lZUUN3ME2yOk44PiCwTR?= Ml;sV2FPT0WU
RS4-11 M3LXS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTJ4LkmxJI5O MYjTRW5ITVJ?
NCI-H292 MlTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUXjUllbUUN3ME2yO{BvVQ>? MWLTRW5ITVJ?
DB Ml3NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV:xW5B4UUN3ME2yO{4{PiCwTR?= NY\tdXdRW0GQR1XS
SW1088 NVS2PJdVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVv6OXpRUUN3ME2yPE4zQSCwTR?= M1XBNHNCVkeHUh?=
A204 M2\HbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTJ6LkS3JI5O NYHxS2tXW0GQR1XS
A3-KAW MlXsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTLVphKSzVyPUK4MlY1KG6P Mk[0V2FPT0WU
MV-4-11 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\SdGlEPTB;MkiuO{BvVQ>? NXjG[ZBDW0GQR1XS
ES1 MnjXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTJ6Lki0JI5O M4\sRXNCVkeHUh?=
ONS-76 NIL6WpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XaXWlEPTB;MkmuNFUhdk1? MY\TRW5ITVJ?
D-263MG NVi0Z2xjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfWTWM2OD1{OT6zOUBvVQ>? NETwTXJUSU6JRWK=
U-2-OS M3;H[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXnJR|UxRTJ7LkWgcm0> Ml\sV2FPT0WU
T98G NUe1N2t7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTJ7Lki4JI5O M1\EbnNCVkeHUh?=
GI-ME-N NV;iPZFTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFXOOVJKSzVyPUK5MlkyKG6P NHnXOXRUSU6JRWK=
BHT-101 MmrDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTNyLkC1JI5O M{TocHNCVkeHUh?=
NOS-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDKTWM2OD1|MD6xNkBvVQ>? NUXUU21pW0GQR1XS
AsPC-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXq3eHNHUUN3ME2zNE4zKG6P MofsV2FPT0WU
QIMR-WIL NXLjdYtDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYexelNTUUN3ME2zNE43KG6P Ml;FV2FPT0WU
JVM-3 M3vOXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\6N2lEPTB;M{CuPFMhdk1? NUnkOm5{W0GQR1XS
KU-19-19 M1jlZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4fPemlEPTB;M{GuNVMhdk1? M{HsRnNCVkeHUh?=
OVCAR-8 MoXBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTNzLkK2JI5O NVnkWG5{W0GQR1XS
BEN M37h[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjJcGJKSzVyPUOxMlY{KG6P MUfTRW5ITVJ?
BE-13 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrYOXVKSzVyPUOxMlgzKG6P M4HaXHNCVkeHUh?=
EW-18 NUnVTWJ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkS0TWM2OD1|MT64OkBvVQ>? MmfOV2FPT0WU
ECC10 M1PpWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFftWHRKSzVyPUOxMlk2KG6P MXHTRW5ITVJ?
CTV-1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTN{LkiyJI5O NH;MUJdUSU6JRWK=
COLO-800 NWfC[o9QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NICwVo9KSzVyPUOyMlkzKG6P M2XXcHNCVkeHUh?=
A2058 MmWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTN|LkK1JI5O NED4WFNUSU6JRWK=
VM-CUB-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXHSO3ZOUUN3ME2zN{41OyCwTR?= M2HmOnNCVkeHUh?=
Ca9-22 M4exXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3S5SGlEPTB;M{OuOVUhdk1? M4nDcHNCVkeHUh?=
COLO-684 NFXQWpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\qNnBKSzVyPUOzMlU5KG6P M{HEeHNCVkeHUh?=
RPMI-8226 MonxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\LTWM2OD1|Mz64NkBvVQ>? MlfUV2FPT0WU
SK-NEP-1 NY\6[|BjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULzNpczUUN3ME2zOE4yPSCwTR?= MnLxV2FPT0WU
Becker NFLOSm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2O3[mlEPTB;M{SuNlEhdk1? M{Lac3NCVkeHUh?=
NCI-H28 NHmxfnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXTcFY4UUN3ME2zOE41PCCwTR?= MoTWV2FPT0WU
CAL-120 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEDWPHNKSzVyPUO0MlczKG6P NV\kNFliW0GQR1XS
MDA-MB-157 Ml[wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;nemlEPTB;M{WuOFEhdk1? M{G4UnNCVkeHUh?=
OVCAR-5 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrDO4xKSzVyPUO1MlQ4KG6P NWPzV5lSW0GQR1XS
LAMA-84 M1HVS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoD5TWM2OD1|NT64O{BvVQ>? M2PzUHNCVkeHUh?=
CAKI-1 M2fRTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3i0dWlEPTB;M{[uOFMhdk1? M{PrSXNCVkeHUh?=
Daoy NUPQb4JmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3zdXRKSzVyPUO2Mlchdk1? NFn5N3dUSU6JRWK=
CAL-62 M2fvU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTN4Lki2JI5O NUjwVYpuW0GQR1XS
8-MG-BA NXL6WmZ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVPBb3QxUUN3ME2zO{4zPSCwTR?= MYTTRW5ITVJ?
8505C M1TtPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TVbmlEPTB;M{euOVEhdk1? NI\LT|dUSU6JRWK=
LNCaP-Clone-FGC M3m3Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYT4O5dVUUN3ME2zO{42QSCwTR?= MlTnV2FPT0WU
CAL-39 NWnueoM2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4XodGlEPTB;M{euPUBvVQ>? M2PNZnNCVkeHUh?=
MN-60 NXXmfIF3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHi2U5pKSzVyPUO3Mlk3KG6P M37s[XNCVkeHUh?=
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COLO-678 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjJR|UxRTJwOEO3Olgh|ryP NX7ld2F1W0GQR1XS
SK-N-DZ NHHyW|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXjEPVdRUUN3ME2yMlg3OzhzIN88US=> NV;vOlJZW0GQR1XS
NCI-H82 MnrUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnjZ2Y{UUN3ME2yMlkxOzZ7IN88US=> NVy2eFU1W0GQR1XS
JVM-2 NXvrSnliT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\NTWM2OD1|LkCzNVg5KM7:TR?= NGO1UnNUSU6JRWK=
SW1116 M4XFbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rGSGlEPTB;Mz6wOVQyOSEQvF2= M{XVWnNCVkeHUh?=
MDA-MB-453 MmfzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXz6dmg1UUN3ME2zMlExPDN7IN88US=> NGnOe4xUSU6JRWK=
Calu-6 MlWyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\uVYFvUUN3ME2zMlE6QTdizszN MXrTRW5ITVJ?
SHP-77 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7WTWM2OD1|LkWyPEDPxE1? MWnTRW5ITVJ?
Capan-2 NVzofVJJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvoTWM2OD12LkOyOVgyKM7:TR?= MWrTRW5ITVJ?
SW948 NVzmbGh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTRwN{S3O|kh|ryP MmLsV2FPT0WU
HDLM-2 NVXORXZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\NRohKSzVyPUWuNFc4OjVizszN MXrTRW5ITVJ?
LAN-6 MoPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXL1dI1pUUN3ME22MlIyPDl3IN88US=> M3qxdHNCVkeHUh?=
LU-135 NUKxbXljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPFTWM2OD14LkSzNFc4KM7:TR?= MnrMV2FPT0WU
T84 M{jCdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHTWYZyUUN3ME22Mlk5PjRizszN MVLTRW5ITVJ?
CAPAN-1 NH7ScVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1vsOmlEPTB;Nz62NlI{OyEQvF2= NFztW29USU6JRWK=
SW1417 NF3Tco1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWGyT4tsUUN3ME23MlkyPzNzIN88US=> MYrTRW5ITVJ?
BALL-1 MljzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4j2VmlEPTB;OD61NFQxQSEQvF2= NVTYcmxKW0GQR1XS
HT-29 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfVWJNFUUN3ME25MlA4PTl7IN88US=> M3Toe3NCVkeHUh?=
C3A MoDBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXz1VFdnUUN3ME25Mlg5Ozl2IN88US=> MYPTRW5ITVJ?
NCI-H1993 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljKTWM2OD1zMD61NFgyKM7:TR?= Ml3uV2FPT0WU
SK-MEL-1 M1T5PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTFzLk[yPFkh|ryP NIj5PZVUSU6JRWK=
DU-145 Mk\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2Hue2lEPTB;MUSuOVA2OiEQvF2= NWD4NYtiW0GQR1XS
KP-N-YN NUL1PFUyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX3JR|UxRTF2LkWxNFMh|ryP NF\UbXpUSU6JRWK=
CCRF-CEM NXnhN5hCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFfVdJJKSzVyPUG0Mlc5ODlizszN MkjWV2FPT0WU
ZR-75-30 NYrzdohsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXM[3RKSzVyPUG2MlM{ODNizszN M2TOdnNCVkeHUh?=
A673 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3:zVWlEPTB;MkCuOVUxPyEQvF2= MkfIV2FPT0WU
K-562 NFvkVZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTRTWM2OD1{OD60NVg{KM7:TR?= NVq3VVl{W0GQR1XS

... 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:
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
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

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

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

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

Dilution Calculator

Dilution Calculator

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

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

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

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

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Molecular Weight Calculator

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
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