Dactolisib (BEZ235)

Catalog No.S1009 Synonyms: NVP-BEZ235

For research use only.

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. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.

Dactolisib (BEZ235) Chemical Structure

CAS No. 915019-65-7

Selleck's Dactolisib (BEZ235) has been cited by 424 publications

Purity & Quality Control

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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. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
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)
Click to View More Targets
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 MVvBcpRqdWmlcn;ibYFtKEG|c3H5 MXixPEBp MljxSG1UVw>? NIS3bHVCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDhyNUm0Okc,OjR6MEW5OFY9N2F-
MCF7 NVH1[3U3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVmwMlAyNTFyMDFOwG0> MlfrOFghcA>? MV7EUXNQ Mkf3TWM2OD1yLkezJO69VQ>? MlrXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6N{G5NFQoRjJ|OEexPVA1RC:jPh?=
HCT116 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjndJYxNjBzLUGwNEDPxE1? NGrN[JM1QCCq NHTvfoNFVVOR NVS5N3dbUUN3ME2xMlE3KM7:TR?= MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5MUmwOEc,OjN6N{G5NFQ9N2F-
U87MG NVTT[WNDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rw[|AvODFvMUCwJO69VQ>? NGjuNlg1QCCq MUfEUXNQ NHGyWZZKSzVyPUGuN|Ih|ryP MoDiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6N{G5NFQoRjJ|OEexPVA1RC:jPh?=
HBC4 NV\pcG04T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDqWmdIOC5yMT2xNFAh|ryP NFvJPFg1QCCq MYHMc4chT0l3ME2tPE43OSCP M2rUNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
BSY1 M4n2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWrsT3UzOC5yMT2xNFAh|ryP NFXZOWw1QCCq NUH6cYMyVG:pIFfJOVA:NThwNEigUS=> NIfZNWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
HBC5 NXixZWI{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV6wMlAyNTFyMDFOwG0> MknSOFghcA>? NULNd2p{VG:pIFfJOVA:NTdwOEegUS=> MnHQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MCF7 M4jGWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHeyWGsxNjBzLUGwNEDPxE1? M4rIT|Q5KGh? NGHOfGRNd2diR1m1NF0uQC5zNjDN NITqZXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
MDA-MB-231 MlrWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4nPUlAvODFvMUCwJO69VQ>? MY[0PEBp NXf3Ro55VG:pIFfJOVA:NThwMEmgUS=> M1PwdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
U251 M1TGTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYqycI85OC5yMT2xNFAh|ryP MkHHOFghcA>? NIfmdIhNd2diR1m1NF0uPy54NjDN MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SF268 Ml3VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTvSYdOOC5yMT2xNFAh|ryP MmW2OFghcA>? M2HEdWxw\yCJSUWwQU04Njl{IF2= Ml7iQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
SF295 NEHiSIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVz0PY9uOC5yMT2xNFAh|ryP NEfoRYU1QCCq MoDNUI9oKEeLNUC9MVgvOzFiTR?= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SF539 M3LDWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnN[XIxNjBzLUGwNEDPxE1? M{DQeVQ5KGh? NFrzSoVNd2diR1m1NF0uQC53OTDN MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SNB75 M{\RZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVLRc|VQOC5yMT2xNFAh|ryP NHfPeVk1QCCq NUHGNnFmVG:pIFfJOVA:NThwNUigUS=> NGfpWpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SNB78 NVjHc3ZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfNZ4cxNjBzLUGwNEDPxE1? MmjGOFghcA>? M2HrNGxw\yCJSUWwQU05NjZ3IF2= MnvLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
HCC2998 NXXZb5d1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1[xelAvODFvMUCwJO69VQ>? NWLkVWdMPDhiaB?= M4C3e2xw\yCJSUWwQU05NjB3IF2= MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
KM12 NXrkdFlMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnRW5BCOC5yMT2xNFAh|ryP MlXGOFghcA>? Ml\LUI9oKEeLNUC9MVcvPTRiTR?= M2fkTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
HT-29 NHTydXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\GUWkxNjBzLUGwNEDPxE1? MWe0PEBp NWjtXWx2VG:pIFfJOVA:NTdwN{WgUS=> MmToQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
HCT15 NGW4dpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTWS2U6OC5yMT2xNFAh|ryP M1H5VFQ5KGh? Ml3OUI9oKEeLNUC9MVgvODNiTR?= MonxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
HCT116 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzS[VIxNjBzLUGwNEDPxE1? NViwbmJSPDhiaB?= NXThUFNqVG:pIFfJOVA:NTdwNkGgUS=> Ml3lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
NCI-H23 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYGwMlAyNTFyMDFOwG0> NWDJempmPDhiaB?= MmnGUI9oKEeLNUC9MVcvPjRiTR?= M1S1SlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
NCI-H226 M{X3bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3Xa[|AvODFvMUCwJO69VQ>? MoHKOFghcA>? M{HZZ2xw\yCJSUWwQU05NjR2IF2= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H522 NGDBXlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPpd3NOOC5yMT2xNFAh|ryP NYTaeI9WPDhiaB?= MkjWUI9oKEeLNUC9MVgvPDViTR?= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H438 MoPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWWwMlAyNTFyMDFOwG0> M{DrWlQ5KGh? Mnn6UI9oKEeLNUC9MVgvOTFiTR?= MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
A549 NGHUZY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXPvXIpyOC5yMT2xNFAh|ryP M4T1fFQ5KGh? MVjMc4chT0l3ME2tPE4xPyCP M4i3S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
DMS273 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHm5SpAxNjBzLUGwNEDPxE1? M3T1WVQ5KGh? NGS5OXpNd2diR1m1NF0uPy56MDDN MnqxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
DMS114 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYq1enhZOC5yMT2xNFAh|ryP MYK0PEBp NGDsfYdNd2diR1m1NF0uQC5|OTDN NHO3XJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
LOXIMVI MnTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXONE4xOS1zMECg{txO M3T4OVQ5KGh? MmnBUI9oKEeLNUC9MVgvPjZiTR?= MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
OVCAR3 M1qz[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7xVIsxNjBzLUGwNEDPxE1? MmPMOFghcA>? MVrMc4chT0l3ME2tPE4yPyCP MlK1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
OVCAR4 M1yxZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYTDSpV3OC5yMT2xNFAh|ryP MXS0PEBp MnjCUI9oKEeLNUC9MVgvPThiTR?= M2POXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
OVCAR5 NVPjfINVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYi5dFFkOC5yMT2xNFAh|ryP NWX3SHdCPDhiaB?= MVXMc4chT0l3ME2tO{42PyCP NFfQUng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
OVCAR8 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{f2OlAvODFvMUCwJO69VQ>? M2LPTlQ5KGh? NFv2NpZNd2diR1m1NF0uPy56NDDN NH:1R2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SKOV3 NWHyb5BZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2CwPFAvODFvMUCwJO69VQ>? NWHNPHpXPDhiaB?= MorJUI9oKEeLNUC9MVgvPDFiTR?= NGHze4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
RXF631L Mo\1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3WxPFAvODFvMUCwJO69VQ>? M3v0RlQ5KGh? MUPMc4chT0l3ME2tPE4zOSCP M3rNNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
ACHN MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXmwMlAyNTFyMDFOwG0> M1HsZVQ5KGh? Ml3GUI9oKEeLNUC9MVcvQTViTR?= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
St-4 NUWzSnVYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXSNE4xOS1zMECg{txO MoHROFghcA>? MkPVUI9oKEeLNUC9MVcvPDdiTR?= Mlr3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MKN1 M4DrfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml3LNE4xOS1zMECg{txO M2Sw[FQ5KGh? MVrMc4chT0l3ME2tPE41OSCP M{HifFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
MKN7 MmrpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;mfVAvODFvMUCwJO69VQ>? NH21XZg1QCCq NUP4NndFVG:pIFfJOVA:NTdwNkigUS=> NH3GZ3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
MKN28 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPZXFd{OC5yMT2xNFAh|ryP MXi0PEBp MV\Mc4chT0l3ME2tO{4xPyCP M2jwXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
MKN45 M{LITGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorzNE4xOS1zMECg{txO MXe0PEBp MV7Mc4chT0l3ME2tPE4{PCCP NFi4d4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
MKN74 NW\BN5JOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vl[VAvODFvMUCwJO69VQ>? MmXGOFghcA>? MoH6UI9oKEeLNUC9MVcvPDJiTR?= M4Pyb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
DU145 NVrMUVJVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY[wMlAyNTFyMDFOwG0> M3zGc|Q5KGh? MkPWUI9oKEeLNUC9MVgvOTZiTR?= NIDzepg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
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MFE-280 NF;tR2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\5bGZKSzVyPUmuPVkhdk1? MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
A549 M4PZU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MknsTWM2OD1zMD6xOEBvVQ>? Ml\SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
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PA-1 NG\ydoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPwVHNKSzVyPUGxMlgzKG6P Mnr0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
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BB65-RCC MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWq5cnNKUUN3ME2xNk44OiCwTR?= MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
NCI-H1793 MlLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4T6eWlEPTB;MUKuPFIhdk1? NEPoV3c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
KARPAS-45 NHLJ[mlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTF|LkWxJI5O MnjDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
GCT M3HDb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYXxRnpqUUN3ME2xN{43QCCwTR?= MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
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LB2241-RCC NHjwWo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTF2LkCxJI5O MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
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COR-L105 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVrO[JBqUUN3ME2xOU4xPCCwTR?= MnnkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
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CAL-39 MlvXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{L6WGlEPTB;M{euPUBvVQ>? NFHFfFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
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LB1047-RCC M3qwPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzhN21KSzVyPUO4MlgyKG6P MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
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8305C NULuPVFNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjTXmdWUUN3ME20NU45PyCwTR?= NU\5cXJ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
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EPLC-272H M2jMfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjuS4Q{UUN3ME20OE4{QSCwTR?= MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
PSN1 NXfzRW9kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3LCWWlEPTB;NESuOEBvVQ>? MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
NCI-H2452 NG\mb45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MU\JR|UxRTR2LkW4JI5O MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
KS-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTR2Lk[2JI5O NWjuXJNWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
HD-MY-Z NGiwZZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XKWWlEPTB;NESuPVIhdk1? M{DwelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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NOMO-1 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV7ybnkyUUN3ME20OU45PyCwTR?= M1nJWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
SK-HEP-1 NE\pTVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHxTWM2OD12Nj6wOEBvVQ>? M4fQT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
IGR-1 NHi0[ZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LsUmlEPTB;NE[uNVMhdk1? MnnuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
KYSE-180 NY\LXlBDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTyTWM2OD12Nj6xO{BvVQ>? NHHTSIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
EW-22 NYDM[JVoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXTTWM2OD12Nj6yJI5O NHzadFE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
NCI-H1355 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnMR4xZUUN3ME20Ok4{PCCwTR?= M37XcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
DOHH-2 MnvJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXsfohTUUN3ME20Ok4{PyCwTR?= MlHDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
A4-Fuk NE\vTVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mle3TWM2OD12Nj61NkBvVQ>? M{G3dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
PC-14 NH\DW3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXsZVdKSzVyPUS2MlU4KG6P MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
TE-5 MonhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXjJR|UxRTR4Lki0JI5O NEXQe3U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
LB996-RCC NEm5cIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2iwUWlEPTB;NEeuNVkhdk1? MlHmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
NCI-H1623 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjhTWM2OD12Nz63OkBvVQ>? M4LyV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
NCI-H1155 NWT0WGVTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4XoSGlEPTB;NEiuN|Ihdk1? M1TBVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
LoVo NV\wNXdTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1[xUWlEPTB;NEiuOEBvVQ>? MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
MCF7 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVK4O5hWUUN3ME20PE42QCCwTR?= MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
AGS NIjnUFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfpTWM2OD12OD63O{BvVQ>? M{\2cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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Calu-6 MlTjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTkTWM2OD1|LkG5PVch|ryP MnnsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
SHP-77 NH32T4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLkTWM2OD1|LkWyPEDPxE1? M{DSXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
Capan-2 Ml[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTRwM{K1PFEh|ryP MlnRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
SW948 M124R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLtRZpPUUN3ME20Mlc1Pzd7IN88US=> MoK0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
HDLM-2 M2XhPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTVwMEe3NlUh|ryP NFfSOWQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
LAN-6 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrJTWM2OD14LkKxOFk2KM7:TR?= NVTpW2lxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
LU-135 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrnN49KSzVyPU[uOFMxPzdizszN Ml7kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
T84 NW\MSlV5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFv2SWhKSzVyPU[uPVg3PCEQvF2= NFnJTIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
CAPAN-1 NHjjXJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljxTWM2OD15Lk[yNlM{KM7:TR?= MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
SW1417 M{Cxdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M170OmlEPTB;Nz65NVc{OSEQvF2= M1fnN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
BALL-1 NYrYT5lVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY\NcFIxUUN3ME24MlUxPDB7IN88US=> NWTaXpBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
HT-29 M2HSSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTlwMEe1PVkh|ryP MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
C3A NWrkW2J2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M321OmlEPTB;OT64PFM6PCEQvF2= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
NCI-H1993 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mon4TWM2OD1zMD61NFgyKM7:TR?= M4O2cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
SK-MEL-1 M1r6NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjjXJdbUUN3ME2xNU43Ojh7IN88US=> NYDFXJZlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
DU-145 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjHbWNFUUN3ME2xOE42ODV{IN88US=> Mn\GQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
KP-N-YN NFy5NGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUezSHpoUUN3ME2xOE42OTB|IN88US=> NY\qWXp[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
CCRF-CEM NHn4UXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3z4dWlEPTB;MUSuO|gxQSEQvF2= NIjib4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
ZR-75-30 MmDES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFvTcIJKSzVyPUG2MlM{ODNizszN MkXLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
A673 NGjsO|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGrZe3FKSzVyPUKwMlU2ODdizszN MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
K-562 NYDx[ZF7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU[zeldQUUN3ME2yPE41OTh|IN88US=> NGfYPFQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
Assay
Methods Test Index PMID
Western blot Myc / Vinculin / pT58 Myc ; pAkt / Akt / Skp2 / AR / pS6 / p27 ; p-S6K / S6K / p-Akt / Akt / p-ABL / BCR-ABL ; Bcl-2 / Caspase-3 / Cleaved caspase-3 ; Cyclin D1 / Cyclin D2 ; mTOR / p-mTOR / p70S6K / p-p70S6K ; p-EGFR-Tyr1068 / EGFR / p-HER2-Tyr1221 / p-HER2-Tyr1222 / HER2 / p-HER3-Tyr1289 25934076 24347472 28435223 29581778 21278786
Immunofluorescence SP1 ; p-ErbB2(Y1248) ; LC3 26336820 24675532 23603977
Growth inhibition assay Cell viability (P3, U87) ; Cell viability (breast cancer cells) ; Cell viability (K562, KBM7R) 27542970 28060760 28435223
ELISA VEGF 19671762
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 (from reference)

Kinase Assay:

[1]

  • 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]

  • 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.

Animal Research:

[1]

  • Animal Models: Female Harlan athymic nude mice
  • Dosages: 45 mg/kg
  • Administration: p.o.

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+PEG300 (10+90, v+v)
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 469.55
Formula

C30H23N5O

CAS No. 915019-65-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3N(C2=O)C)C5=CC6=CC=CC=C6N=C5

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01856101 Terminated Drug: BEZ235 Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01717898 Terminated Drug: BEZ235|Drug: Prednisone|Drug: Abiraterone acetate Castrate-resistant Prostate Cancer Charles Ryan|Novartis Pharmaceuticals|University of California San Francisco January 31 2013 Phase 1|Phase 2
NCT01756118 Unknown status Drug: BEZ235 Acute Lymphoblastic Leukemia|Leukemia Myelocytic Acute|Chronic Myelogenous Leukemia With Crisis of Blast Cells Johann Wolfgang Goethe University Hospital June 2012 Phase 1
NCT01290406 Withdrawn Drug: BEZ235 Endometrial Cancer Novartis Pharmaceuticals|Novartis March 2012 Phase 2
NCT01288092 Withdrawn Drug: BEZ235 Metastatic Breast Cancer Novartis Pharmaceuticals|Novartis March 2012 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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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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