Dactolisib (BEZ235)

For research use only.

Catalog No.S1009 Synonyms: NVP-BEZ235

401 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.

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Selleck's Dactolisib (BEZ235) has been cited by 401 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 NU\BSWR6SW62aX3pZ5Jw[mmjbDDBd5NigQ>? MVOxPEBp NYGxbINsTE2VTx?= Mn3FRY51cXS{eYDhco9{d22jbDDhZ5Rqfmm2eTD3bZRpKEWFNUCgc4YhOC5yMEK1JO69VQ>? M2XHVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEC1PVQ3Lz5{NEiwOVk1PjxxYU6=
MCF7 NXnyd2ZIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWmwMlAyNTFyMDFOwG0> Mk\ROFghcA>? NGrtbZZFVVOR MkDjTWM2OD1yLkezJO69VQ>? MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5MUmwOEc,OjN6N{G5NFQ9N2F-
HCT116 M4Lve2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTlTIJCOC5yMT2xNFAh|ryP NXjBd|NWPDhiaB?= MVXEUXNQ MV\JR|UxRTFwMU[g{txO M{f6WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEexPVA1Lz5{M{i3NVkxPDxxYU6=
U87MG NH\QenhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnTNE4xOS1zMECg{txO NHfkTIk1QCCq MXTEUXNQ MW\JR|UxRTFwM{Kg{txO NGHJenA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3NVkxPCd-MkO4O|E6ODR:L3G+
HBC4 NIrLfZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVGyflhKOC5yMT2xNFAh|ryP M4jNV|Q5KGh? NXO5[2RZVG:pIFfJOVA:NThwNkGgUS=> MkH4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
BSY1 MoPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYT2RW14OC5yMT2xNFAh|ryP M3G1WlQ5KGh? NEPYRmlNd2diR1m1NF0uQC52ODDN MkH2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
HBC5 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVy0OpppOC5yMT2xNFAh|ryP NHu0O5Y1QCCq NGOxfppNd2diR1m1NF0uPy56NzDN Ml3PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MCF7 NYr5SXNiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTFNVZjOC5yMT2xNFAh|ryP M{HkXlQ5KGh? M4i5[2xw\yCJSUWwQU05NjF4IF2= M1exVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
MDA-MB-231 M1W0Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmi5NE4xOS1zMECg{txO M{TXTFQ5KGh? MUPMc4chT0l3ME2tPE4xQSCP Mn;zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
U251 NILGNWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2GzSFAvODFvMUCwJO69VQ>? M2KxVVQ5KGh? MXjMc4chT0l3ME2tO{43PiCP MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SF268 NGrpeHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWSwMlAyNTFyMDFOwG0> MYm0PEBp MUTMc4chT0l3ME2tO{46OiCP M3u3TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
SF295 NG\ReGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWOwMlAyNTFyMDFOwG0> NVrX[XVyPDhiaB?= MkDQUI9oKEeLNUC9MVgvOzFiTR?= NFrNcmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SF539 M4L6bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4K1bVAvODFvMUCwJO69VQ>? NHzWeGM1QCCq NXnLWYh2VG:pIFfJOVA:NThwNUmgUS=> MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
SNB75 NWThVZd[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjQXmcxNjBzLUGwNEDPxE1? NHrIWmg1QCCq MVPMc4chT0l3ME2tPE42QCCP NFjHdIg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SNB78 NVLvdGZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnaSpoxNjBzLUGwNEDPxE1? NVTD[25PPDhiaB?= MUPMc4chT0l3ME2tPE43PSCP NWrjO2ppRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
HCC2998 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3myN|AvODFvMUCwJO69VQ>? NYHIclZTPDhiaB?= M1nXXmxw\yCJSUWwQU05NjB3IF2= NFPoOXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
KM12 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTZWlJIOC5yMT2xNFAh|ryP MX:0PEBp NEPnT2dNd2diR1m1NF0uPy53NDDN MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
HT-29 M2jkPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXhSnk3OC5yMT2xNFAh|ryP NEH1UXM1QCCq MlfLUI9oKEeLNUC9MVcvPzViTR?= M4HFSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
HCT15 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPNNE4xOS1zMECg{txO NEPVNG81QCCq MmDIUI9oKEeLNUC9MVgvODNiTR?= MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
HCT116 NGHVXHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFm2d4UxNjBzLUGwNEDPxE1? NG\JRmQ1QCCq M17YfGxw\yCJSUWwQU04NjZzIF2= NEX0[VM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
NCI-H23 MlHmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYn3dm0zOC5yMT2xNFAh|ryP MmrCOFghcA>? NGrIPWdNd2diR1m1NF0uPy54NDDN NFS5N2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
NCI-H226 MnTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTiNE4xOS1zMECg{txO M{H3OVQ5KGh? MmXmUI9oKEeLNUC9MVgvPDRiTR?= MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
NCI-H522 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2CwRVAvODFvMUCwJO69VQ>? MojoOFghcA>? NHzacVRNd2diR1m1NF0uQC52NTDN MoXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
NCI-H438 MmDDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWOwMlAyNTFyMDFOwG0> MUK0PEBp MWTMc4chT0l3ME2tPE4yOSCP MnroQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
A549 M37oNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUmwMlAyNTFyMDFOwG0> NY\zSZFYPDhiaB?= NFP3WFBNd2diR1m1NF0uQC5yNzDN MmHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
DMS273 NYLJVm1RT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1XHRlAvODFvMUCwJO69VQ>? NIexfHA1QCCq Mnj4UI9oKEeLNUC9MVcvQDBiTR?= NV;hWZY5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
DMS114 NYXwRmJ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnv1NE4xOS1zMECg{txO NXzkToF7PDhiaB?= MkDWUI9oKEeLNUC9MVgvOzliTR?= NIDI[Jc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
LOXIMVI MljOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HkZ|AvODFvMUCwJO69VQ>? NIHScnA1QCCq MWDMc4chT0l3ME2tPE43PiCP MmTwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
OVCAR3 NXy0TpdpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF61ZocxNjBzLUGwNEDPxE1? NF3FOHc1QCCq Mnv0UI9oKEeLNUC9MVgvOTdiTR?= NYCyUXZ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
OVCAR4 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1nCc|AvODFvMUCwJO69VQ>? M4faVFQ5KGh? NGHGVIZNd2diR1m1NF0uQC53ODDN M2LDc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
OVCAR5 NYP6bINLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUiwMlAyNTFyMDFOwG0> Mki2OFghcA>? MVrMc4chT0l3ME2tO{42PyCP MmHQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
OVCAR8 M1rOXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXT2eolROC5yMT2xNFAh|ryP M2TJdlQ5KGh? M4nK[Wxw\yCJSUWwQU04Njh2IF2= NFnOfm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
SKOV3 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{LaT|AvODFvMUCwJO69VQ>? MnP2OFghcA>? NYHJZXZYVG:pIFfJOVA:NThwNEGgUS=> MlTYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
RXF631L NYnKeGV1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTzNE4xOS1zMECg{txO NGHpfmQ1QCCq NILzZmFNd2diR1m1NF0uQC5{MTDN Mnz0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
ACHN NU\Mb2xST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYqwMlAyNTFyMDFOwG0> NHfaOXY1QCCq MlrkUI9oKEeLNUC9MVcvQTViTR?= NUXl[JRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
St-4 NWPITIZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXuwMlAyNTFyMDFOwG0> NFy5ZoM1QCCq MkTiUI9oKEeLNUC9MVcvPDdiTR?= M2S3NlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{O2NlQ3Lz5{MkOzOlI1PjxxYU6=
MKN1 NHTrZmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWL2W5NXOC5yMT2xNFAh|ryP MnXBOFghcA>? MYHMc4chT0l3ME2tPE41OSCP NWSxO2o3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzN|YzPDZpPkKyN|M3OjR4PD;hQi=>
MKN7 NFrZXnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfre2VnOC5yMT2xNFAh|ryP NVjHcWd2PDhiaB?= NV\nd|ZRVG:pIFfJOVA:NTdwNkigUS=> Mmj3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MKN28 NFrZO5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWOwMlAyNTFyMDFOwG0> MVu0PEBp MmLXUI9oKEeLNUC9MVcvODdiTR?= MnrTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
MKN45 M1q2Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYSwMlAyNTFyMDFOwG0> NW\RNWVmPDhiaB?= Mn6yUI9oKEeLNUC9MVgvOzRiTR?= MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN|NkK0Okc,OjJ|M{[yOFY9N2F-
MKN74 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2Pz[lAvODFvMUCwJO69VQ>? MYq0PEBp M1Hoemxw\yCJSUWwQU04NjR{IF2= MlfqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|M{[yOFYoRjJ{M{O2NlQ3RC:jPh?=
DU145 M3H5Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33BTlAvODFvMUCwJO69VQ>? NHLQNWo1QCCq M4r0S2xw\yCJSUWwQU05NjF4IF2= NH\Jb3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkOzOlI1Pid-MkKzN|YzPDZ:L3G+
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NCI-H2452 NHXHcZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4OxfmlEPTB;NESuOVghdk1? NH\WdIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
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KYSE-180 NWnhT5k3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrEeotnUUN3ME20Ok4yPyCwTR?= MkHWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
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NCI-H1355 NELIXGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjHZ3pzUUN3ME20Ok4{PCCwTR?= NY\a[pAzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
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PC-14 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XiVmlEPTB;NE[uOVchdk1? M1\sfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
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LB996-RCC M4TDS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{e0TGlEPTB;NEeuNVkhdk1? NHXiUIc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
NCI-H1623 MmjtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnGTWM2OD12Nz63OkBvVQ>? MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
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NCI-H82 MkSwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYm2fWl5UUN3ME2yMlkxOzZ7IN88US=> NYnrdY1MRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
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Capan-2 M3HqZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmrpTWM2OD12LkOyOVgyKM7:TR?= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
SW948 NGTKc4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HEeGlEPTB;ND63OFc4QSEQvF2= NFvHZWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
HDLM-2 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLuTWM2OD13LkC3O|I2KM7:TR?= NVPte5J7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
LAN-6 NUTac5p3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTY[5BRUUN3ME22MlIyPDl3IN88US=> NI\lblA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
LU-135 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTZwNEOwO|ch|ryP NF;4bG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
T84 M2jCW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLYd49KSzVyPU[uPVg3PCEQvF2= MkDKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
CAPAN-1 NYD0Um1TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3POPWlEPTB;Nz62NlI{OyEQvF2= NUHFVGlMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
SW1417 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;pOGlEPTB;Nz65NVc{OSEQvF2= M3m3TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
BALL-1 NXGwRmxRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRThwNUC0NFkh|ryP NX25[2tyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTh5OUS2N{8oRlODTlfFVlww[T5?
HT-29 M2rU[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvOTWM2OD17LkC3OVk6KM7:TR?= M{e5SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
C3A NXq5bmtiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT3ZWFKSzVyPUmuPFg{QTRizszN MoKwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
NCI-H1993 M2nKVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjxPWtKSzVyPUGwMlUxQDFizszN MkLVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
SK-MEL-1 NXz0b4lFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHm2d3hKSzVyPUGxMlYzQDlizszN NEjJeJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
DU-145 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{i3dmlEPTB;MUSuOVA2OiEQvF2= MnP5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>
KP-N-YN NYfqc4FjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1WzWWlEPTB;MUSuOVExOyEQvF2= NGTFb|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
CCRF-CEM NEfUdFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUPJR|UxRTF2Lke4NFkh|ryP NFP4OIc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQDd7NE[zM{c,W0GQR1XSQE9iRg>?
ZR-75-30 NGjXVGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\1TWM2OD1zNj6zN|A{KM7:TR?= M2jMU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE5Pzl2NkOvK|5USU6JRWK8M4E,
A673 NGW0VYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LEWGlEPTB;MkCuOVUxPyEQvF2= MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPFc6PDZ|Lze+V2FPT0WUPD;hQi=>
K-562 NU\IRVU2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTJ6LkSxPFMh|ryP Ml7PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVg4QTR4Mz:nQnNCVkeHUkyvZV4>

... 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]

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  • 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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    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
NCT01482156 Completed Drug: RAD001 + BEZ235 Advanced Solid Tumors|Metastatic Breast Cancer|Metastatic Renal Cell Carcinoma Novartis Pharmaceuticals|Novartis January 2012 Phase 1
NCT01337765 Completed Drug: BEZ235 + MEK162 Unspecified Adult Solid Tumor Protocol Specific|Solid Tumor Pfizer July 8 2011 Phase 1

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.

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID