Dactolisib (BEZ235)

For research use only.

Catalog No.S1009 Synonyms: NVP-BEZ235

408 publications

Dactolisib (BEZ235) Chemical Structure

CAS No. 915019-65-7

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.

Selleck's Dactolisib (BEZ235) has been cited by 408 publications

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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)
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 M4G1UmFvfGmvaXPyc4Jq[WxiQYPzZZk> NYPOPJRZOThiaB?= Mn7kSG1UVw>? MorFRY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? NVW2VnFoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4NFU6PDZpPkK0PFA2QTR4PD;hQi=>
MCF7 NHfTWI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3;BflAvODFvMUCwJO69VQ>? MlXDOFghcA>? NU\ncmtSTE2VTx?= M{fmUGlEPTB;MD63N{DPxE1? NG[xTGc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3NVkxPCd-MkO4O|E6ODR:L3G+
HCT116 NFq0ZYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPjNE4xOS1zMECg{txO NELpeVA1QCCq MYHEUXNQ NVXrV|BrUUN3ME2xMlE3KM7:TR?= Mly1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6N{G5NFQoRjJ|OEexPVA1RC:jPh?=
U87MG M17hTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXiwMlAyNTFyMDFOwG0> MYi0PEBp NV3zVpZ5TE2VTx?= Mon2TWM2OD1zLkOyJO69VQ>? M{fOWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEexPVA1Lz5{M{i3NVkxPDxxYU6=
HBC4 NF;ucnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDIO49kOC5yMT2xNFAh|ryP M{DIU|Q5KGh? MlK2UI9oKEeLNUC9MVgvPjFiTR?= NYTGU4ZMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
BSY1 M3;nXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTUNE4xOS1zMECg{txO NInPcYw1QCCq NHjS[4ZNd2diR1m1NF0uQC52ODDN MkXLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
HBC5 Mke2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGrQ[5gxNjBzLUGwNEDPxE1? Mo[0OFghcA>? MontUI9oKEeLNUC9MVcvQDdiTR?= MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
MCF7 NYnre|JQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;X[IZmOC5yMT2xNFAh|ryP NVPBNoE1PDhiaB?= NF7QcJNNd2diR1m1NF0uQC5zNjDN NF7tVnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
MDA-MB-231 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4flSVAvODFvMUCwJO69VQ>? MVq0PEBp M3[1WWxw\yCJSUWwQU05NjB7IF2= MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
U251 NX\PSXBST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULHfm1tOC5yMT2xNFAh|ryP MYO0PEBp NGO3dFdNd2diR1m1NF0uPy54NjDN NFHDUmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SF268 NFXtO|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vBbVAvODFvMUCwJO69VQ>? NWDHbnptPDhiaB?= NHjENHdNd2diR1m1NF0uPy57MjDN NXHSS5p{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
SF295 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nWUVAvODFvMUCwJO69VQ>? M{LkXlQ5KGh? NFLFfnhNd2diR1m1NF0uQC5|MTDN MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SF539 M1Lhdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{DY[|AvODFvMUCwJO69VQ>? MmLYOFghcA>? NHz1[IlNd2diR1m1NF0uQC53OTDN MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SNB75 NFzDSVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\0dGptOC5yMT2xNFAh|ryP M4HrUFQ5KGh? NHm5Rm1Nd2diR1m1NF0uQC53ODDN M3\GVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
SNB78 M4H2Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXrVpZiOC5yMT2xNFAh|ryP M3ryclQ5KGh? NEDYZ3dNd2diR1m1NF0uQC54NTDN NXi5d5NKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
HCC2998 M4q5bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnrSoYxNjBzLUGwNEDPxE1? MYG0PEBp M2\rWWxw\yCJSUWwQU05NjB3IF2= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
KM12 NI\4XIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXnNE4xOS1zMECg{txO MVW0PEBp MkTEUI9oKEeLNUC9MVcvPTRiTR?= NYH1fpRXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
HT-29 NXTW[|BCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmr4NE4xOS1zMECg{txO NVzCXGNLPDhiaB?= M1\pZWxw\yCJSUWwQU04Njd3IF2= M16wT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
HCT15 MnvKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWGwMlAyNTFyMDFOwG0> NFHwfWs1QCCq M2TOfmxw\yCJSUWwQU05NjB|IF2= NVHLVYZwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
HCT116 NFrhPIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYSw[GsxOC5yMT2xNFAh|ryP MVK0PEBp Mn;ZUI9oKEeLNUC9MVcvPjFiTR?= MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H23 NF65T|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXkdnoxNjBzLUGwNEDPxE1? MWS0PEBp MXTMc4chT0l3ME2tO{43PCCP MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H226 M1K5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{[5ZVAvODFvMUCwJO69VQ>? MUO0PEBp MWfMc4chT0l3ME2tPE41PCCP MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H522 M2jQU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYCwMlAyNTFyMDFOwG0> NVvZUHREPDhiaB?= MkjpUI9oKEeLNUC9MVgvPDViTR?= M3qyTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
NCI-H438 MnHwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEWzRWwxNjBzLUGwNEDPxE1? M3jUUVQ5KGh? M2i3[2xw\yCJSUWwQU05NjFzIF2= MnTLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
A549 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorGNE4xOS1zMECg{txO MV:0PEBp M3X4VWxw\yCJSUWwQU05NjB5IF2= Ml:1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
DMS273 M{\Re2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjTNlAxNjBzLUGwNEDPxE1? M2rlWVQ5KGh? NUHCR3Y1VG:pIFfJOVA:NTdwOECgUS=> M{Ple|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
DMS114 NUnCeZdET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIn5[YYxNjBzLUGwNEDPxE1? NYiyfo5rPDhiaB?= NI\NWVNNd2diR1m1NF0uQC5|OTDN Ml3vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
LOXIMVI NVHld4RkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYCwMlAyNTFyMDFOwG0> MoTIOFghcA>? NFrXd3JNd2diR1m1NF0uQC54NjDN NW\FcIl{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
OVCAR3 M{XGbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXHdWYxNjBzLUGwNEDPxE1? M4fzNFQ5KGh? Mm[yUI9oKEeLNUC9MVgvOTdiTR?= M161dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
OVCAR4 M2HPZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnrHNE4xOS1zMECg{txO NETjblU1QCCq M{LTNmxw\yCJSUWwQU05NjV6IF2= MmrxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
OVCAR5 NWH3clRPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPx[optOC5yMT2xNFAh|ryP MYm0PEBp NX;qRW5nVG:pIFfJOVA:NTdwNUegUS=> MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
OVCAR8 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV6y[IlUOC5yMT2xNFAh|ryP M2HKcVQ5KGh? MoH5UI9oKEeLNUC9MVcvQDRiTR?= MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SKOV3 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVuwMlAyNTFyMDFOwG0> NIPJWXQ1QCCq M3PFR2xw\yCJSUWwQU05NjRzIF2= NXPrUZlTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
RXF631L NULWWFJGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUO0S2I4OC5yMT2xNFAh|ryP NGP1dYw1QCCq M3y0cWxw\yCJSUWwQU05NjJzIF2= NGTTO3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
ACHN MnTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHUemUxNjBzLUGwNEDPxE1? MorvOFghcA>? Mlz4UI9oKEeLNUC9MVcvQTViTR?= MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
St-4 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XwWFAvODFvMUCwJO69VQ>? M360bFQ5KGh? MVPMc4chT0l3ME2tO{41PyCP MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
MKN1 MlfnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFO3bo0xNjBzLUGwNEDPxE1? NGTSPJY1QCCq MWfMc4chT0l3ME2tPE41OSCP MlzYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MKN7 NEe5S|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn[zNE4xOS1zMECg{txO M1v5R|Q5KGh? MmrQUI9oKEeLNUC9MVcvPjhiTR?= Ml\qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MKN28 NGm2OZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVqwMlAyNTFyMDFOwG0> NXPXVpMxPDhiaB?= NHjRb41Nd2diR1m1NF0uPy5yNzDN NFvQSGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
MKN45 MkTvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUewMlAyNTFyMDFOwG0> NEjDPY01QCCq MUXMc4chT0l3ME2tPE4{PCCP M1ziWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
MKN74 Ml70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MViwMlAyNTFyMDFOwG0> Mk\GOFghcA>? NX\Z[WdEVG:pIFfJOVA:NTdwNEKgUS=> Ml;TQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
DU145 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MViwMlAyNTFyMDFOwG0> MXS0PEBp NVzueWJTVG:pIFfJOVA:NThwMU[gUS=> NUXTcZNNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
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Trypanosoma brucei brucei NW\BXGV7TnWwY4Tpc44hSXO|YYm= NHXjd5IzODBibl2= NHrKNlcyOiCq NVrT[5NTTE2VTx?= NGPRVVBG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDhyNUm0Okc,OjR6MEW5OFY9N2F-
UM-UC-3 NX:4fZlqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTNzNTDwUS=> MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
SBC-1 NI\QToZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnjOZVtUUN3ME23OFIheE1? MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
MKN1 MnnOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrRXoY6UUN3ME2yMlghdk1? M4e5NFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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BFTC-909 MkPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPGb4NnUUN3ME2zMlcyKG6P M4rVcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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AN3-CA M4jQ[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nocWlEPTB;NT61OkBvVQ>? M4nJSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
HN NVWxb5JUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFjZWlZKSzVyPUWuPVYhdk1? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
HCC2218 M4fnNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXITWM2OD14Lk[xJI5O M{TwNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
KP-4 MkHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTdibl2= NGTjO3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
LU-139 M2XMVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3e0[2lEPTB;Nz63O{BvVQ>? NVfUS5c3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
ETK-1 M3eyXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPoTWM2OD15Lki4JI5O NHLTcI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
Ramos-2G6-4C10 NVi3Z2dyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfJTWM2OD16LkS5JI5O M3XN[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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DU-4475 NXTteY5qT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrPRW9xUUN3ME25MlQ1KG6P NVTkTnkyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
NCI-H1666 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\zWWlEPTB;OT63NUBvVQ>? M2nP[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
CAMA-1 M4jQNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrjNnFKSzVyPUmuPEBvVQ>? MmrtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
TYK-nu NHTTbW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUm3WI1jUUN3ME25Mlk1KG6P NX\CR2FLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
MFE-280 M{PjN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\yVmlEPTB;OT65PUBvVQ>? MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
A549 NWTBNGxDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLBPWhsUUN3ME2xNE4yPCCwTR?= NXPw[lc3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
769-P NVjZcmtIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\jWIwxUUN3ME2xNE41PCCwTR?= NE\uXo09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
L-363 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPMTWM2OD1zMD62PUBvVQ>? NF7UXZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
ES8 MonmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFj4Oo5KSzVyPUGwMlkhdk1? NVfxWmw3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
PA-1 NGPnSWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFzLkiyJI5O NI\vTVc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
Mewo NEHiVGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYeySpRvUUN3ME2xNU46QSCwTR?= NHrGWY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
HSC-3 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnBVYNKSzVyPUGyMlIyKG6P NGnUdnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
H4 NGjWNmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrWUpZjUUN3ME2xNk43PyCwTR?= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
BB65-RCC M4jLdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnuTWM2OD1zMj63NkBvVQ>? NFfpeVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
NCI-H1793 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTF{LkiyJI5O M1i4c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
KARPAS-45 NX;pZpp1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFm2cGtKSzVyPUGzMlUyKG6P MkLVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
GCT NGKySYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPROJI6UUN3ME2xN{43QCCwTR?= MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
EoL-1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFu2[nZKSzVyPUGzMlk{KG6P M2n1NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
LB2241-RCC M334b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mk\qTWM2OD1zND6wNUBvVQ>? MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
ES5 M3GwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVe2d4dYUUN3ME2xOE44PCCwTR?= MmjBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
LOXIMVI M4rEfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWfNSYNGUUN3ME2xOE46QSCwTR?= NHPIfos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
COR-L105 MljYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGWxcoZKSzVyPUG1MlA1KG6P MmLtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
P12-ICHIKAWA MlvlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPqTWM2OD1zNT6xJI5O NGXVW|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
CHL-1 NH7XSWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPrTWM2OD1zNT60OUBvVQ>? NG\XeHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
VMRC-RCZ NYS4[XNvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnezTWM2OD1zNT62N{BvVQ>? MmXCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
HH M363bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13MUWlEPTB;MUWuO{BvVQ>? MnHCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
NUGC-3 M{XQOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXrJR|UxRTF4LkO0JI5O MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
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KARPAS-299 M33je2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnRTWM2OD1zLke5OFc6KM7:TR?= MnrHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
NCI-H358 NFz1UJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXF[VBUUUN3ME2xMlk2PTB|IN88US=> NVTCfmFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
OAW-28 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3HTWM2OD1{LkC2PVE6KM7:TR?= NEflcXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
C8166 MlS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rYSmlEPTB;Mj62N|M6OiEQvF2= MkjnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
COLO-678 M{nPb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfQeIlKSzVyPUKuPFM4PjhizszN NWPrXZpiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
SK-N-DZ NGCzVVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVXqZYxLUUN3ME2yMlg3OzhzIN88US=> NW[wdJJCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
NCI-H82 NX\FNFFlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnrDTWM2OD1{LkmwN|Y6KM7:TR?= NUHOUoQ{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
JVM-2 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIHINJpKSzVyPUOuNFMyQDhizszN MmO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
SW1116 NWi4OmFwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PyPGlEPTB;Mz6wOVQyOSEQvF2= MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
MDA-MB-453 NF3wS4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTNwMUC0N|kh|ryP MnHHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
Calu-6 NWLPN|NyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MojITWM2OD1|LkG5PVch|ryP M136dVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
SHP-77 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLHTWM2OD1|LkWyPEDPxE1? NXvtNGY5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
Capan-2 M1nrVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWnJR|UxRTRwM{K1PFEh|ryP NXn1N|ZmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
SW948 NG\Qc3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUHJR|UxRTRwN{S3O|kh|ryP NWXN[pp4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
HDLM-2 NUHOfHB3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfZTWM2OD13LkC3O|I2KM7:TR?= MkPJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
LAN-6 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoSyTWM2OD14LkKxOFk2KM7:TR?= MlrQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
LU-135 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTE[VM6UUN3ME22MlQ{ODd5IN88US=> NYXDNnI4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
T84 NIPaV|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXmTWM2OD14Lkm4OlQh|ryP MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
CAPAN-1 MlPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTdwNkKyN|Mh|ryP NFK2R3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
SW1417 NIDYfIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HsemlEPTB;Nz65NVc{OSEQvF2= NFXh[2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
BALL-1 M3v5Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRThwNUC0NFkh|ryP MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
HT-29 NVyyNGZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrETWM2OD17LkC3OVk6KM7:TR?= M4LSblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
C3A M{\3WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVLpe|NxUUN3ME25Mlg5Ozl2IN88US=> M3TMTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
NCI-H1993 NH2wT|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFuwfVhKSzVyPUGwMlUxQDFizszN MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
SK-MEL-1 NIX2Oo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PaR2lEPTB;MUGuOlI5QSEQvF2= NYnLVo14RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
DU-145 NGLkWmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTF2LkWwOVIh|ryP MlPpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
KP-N-YN MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYrJR|UxRTF2LkWxNFMh|ryP Mn30QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
CCRF-CEM NH7TU|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTPPFI6UUN3ME2xOE44QDB7IN88US=> M4HUelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
ZR-75-30 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3nDZ2lEPTB;MU[uN|MxOyEQvF2= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
A673 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrre4hKSzVyPUKwMlU2ODdizszN Ml7wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
K-562 M{i2OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzTcmdKSzVyPUK4MlQyQDNizszN MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Myc / Vinculin / pT58 Myc; 

PubMed: 25934076     


Immunoblots documenting MYC and pT58 MYC stability. SW480 cells were treated with 200nM BEZ235 or solvent control for 24h and cycloheximide (50µg/ml) and harvested at the indicated time points. Vinculin was used as loading control. Exposures of MYC and pT58 MYC blots were adjusted to equalize exposure at 0 min (n=3; unless otherwise indicated, n indicates the number of independent biological repeat experiments in the following legends).

pAkt / Akt / Skp2 / AR / pS6 / p27; 

PubMed: 24347472     


BEZ235 decreases Skp2 and increases AR protein expression inC4-2B cells. Cells were treated with BEZ235 at various doses. Cell lysates were subjected to Westernblot analysis with indicated antibodies. 

p-S6K / S6K / p-Akt / Akt / p-ABL / BCR-ABL; 

PubMed: 28435223     


Dose-dependent inhibition effect of BEZ235 on the phosphorylation levels of S6K, Akt (Ser473), and BCR–ABL in CML cells. Results of Western blot.

Bcl-2 / Caspase-3 / Cleaved caspase-3 ; 

PubMed: 28435223     


K562 (A1) and KBM7R (A2) cells were treated with BEZ235 for 24 h; total protein lysates were immunoblotted with antibodies for Bcl-2, caspase-3, and cleaved caspase-3. 

Cyclin D1 / Cyclin D2 ; 

PubMed: 28435223     


Dose-dependent inhibition effect of BEZ235 on the expression levels of cyclin D1 and cyclin D2 in K562 and KBM7R cells. Western blot results of K562 (A1) and KBM7R (A2) cells.

mTOR / p-mTOR / p70S6K / p-p70S6K ; 

PubMed: 29581778     


Eca-109 cells was treated with increasing concentration of BEZ235 (0, 100, 200 and 500 nM) for 48 hours. Western blot showed the inhibition effect of PI3K/mTOR pathway was dose dependent. 

p-EGFR-Tyr1068 / EGFR / p-HER2-Tyr1221 / p-HER2-Tyr1222 / HER2 / p-HER3-Tyr1289; 

PubMed: 21278786     


Immunoblots of protein lysates from BT474 and MCF7-HER2 cells treated with either BEZ235 alone (0–500 n) or the combination of BEZ235 (0–500 n) and the tyrosine kinase inhibitor lapatinib (LAP, 500 n) for 24 h. 

25934076 24347472 28435223 29581778 21278786
Immunofluorescence
SP1; 

PubMed: 26336820     


Immunofluorescence assessment of SP1 after BEZ235 treatment for 24 hrs in A673, SKNMC cells and in HFF.

p-ErbB2(Y1248); 

PubMed: 24675532     


Immunofluorescence staining of BT474.LapR cells grown in 3-D culture under different treatment conditions for a week. Scale bar indicates 50 μm.

LC3; 

PubMed: 23603977     


(A) SU-2 cells were treated with NVP-BEZ235 (10 nmol/L) for 12 h and then harvested 24 h after treatment with IR (8 Gy), and analyzed for LC3 expression (top) or the formation of autophagolysosomes by using MDC (middle) and LTR (bottom) by immunofluorescence analysis (600×magnification).

26336820 24675532 23603977
Growth inhibition assay
Cell viability (P3, U87); 

PubMed: 27542970     


IC50 doses of dactolisib for P3 (left) and U87 (right) glioma cells, generated from MTS assay. 

Cell viability (breast cancer cells); 

PubMed: 28060760     


Cell viability of breast cancer cells treated by either BEZ235 or TSA for 48h was measured by MTT assay. Each cell line was analyzed in triplicate, and a representative experiment is shown. 

Cell viability (K562, KBM7R); 

PubMed: 28435223     


(A) K562 cells were treated with increasing concentrations of BEZ235 for 24, 48, or 72 h and subjected to MTS assay. (B) KBM7R cells were treated with increasing concentrations of BEZ235 for 24, 48, or 72 h and subjected to MTS assay. (C) K562 cells were treated with imatinib (0–10 μM) alone or imatinib and BEZ235 (0.2 μM) for 48 h and subjected to MTS assay. (D) KBM7R cells were treated with imatinib (0–10 μM) alone or imatinib and BEZ235 (0.2 μM) for 48 h and subjected to MTS assay. Mean ± SD. n=3. *P<0.05, compared to the control group. #P<0.05, compared to the group of IM alone.

27542970 28060760 28435223
ELISA
VEGF; 

PubMed: 19671762     


NVP-BEZ235 attenuated VEGF secretion by at least 40% in U87 cells. The VEGF level in the serum-free medium was measured in triplicate and the experiment repeated at least twice to confirm results.

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

Kinase Assay:

[1]

- Collapse

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]

- Collapse
  • 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]

- Collapse
  • Animal Models: Female Harlan athymic nude mice
  • 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+PEG300 (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 NVP-BEZ235
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

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Dilution Calculator

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

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

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

  • C1
    V1
    C2
    V2

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

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

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

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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

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.

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID