BEZ235 (NVP-BEZ235, Dactolisib) 化学構造
分子量: 469.55

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Quality Control & MSDS

製品説明

  • Compare PI3K Inhibitors
    PI3K製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 BEZ235 (NVP-BEZ235, Dactolisib)は競争性的なPI3K、mTOR 阻害剤、 p110α, p110γ, p110δ と p110β を作用すると、 IC50 がぞれぞれ 4 nM, 5 nM, 7 nM と 75 nMになる.
ターゲット

p110α

p110γ

p110δ

p110β

ATR

IC50

4 nM

5 nM

7 nM

75 nM [1]

21 nM [8]

In vitro試験 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
Trypanosoma brucei brucei Mn64RY51cW2rY4LvZolidCCDc4PhfS=> Moe2NVghcA>? NXOxSpBWTE2VTx?= MYHBcpRqfHK7cHHuc5NwdWGuIHHjeIl3cXS7IIfpeIghTUN3MDDv[kAxNjByMkWg{txO NVjrVINZOjR6MEW5OFY>
MCF7 NXLURWpUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\6NYgxNjBzLUGwNEDPxE1? M{PQO|Q5KGh? NIn2fYtFVVOR MkLqTWM2OD1yLkezJO69VQ>? NFXPcW8zOzh5MUmwOC=>
HCT116 M4\WfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHHMNGsxNjBzLUGwNEDPxE1? MXm0PEBp MWHEUXNQ MXnJR|UxRTFwMU[g{txO MoDjNlM5PzF7MES=
U87MG MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEDEPFQxNjBzLUGwNEDPxE1? NVrFeVNNPDhiaB?= NUfEOm85TE2VTx?= MVXJR|UxRTFwM{Kg{txO NVmwRZlqOjN6N{G5NFQ>
HBC4 NX;MVmxQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGH5SngxNjBzLUGwNEDPxE1? MoTZOFghcA>? MWHMc4chT0l3ME2tPE43OSCP NWqwRoRiOjJ|M{[yOFY>
BSY1 NF3nOIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIq4fmQxNjBzLUGwNEDPxE1? M13HVFQ5KGh? NGXBNFlNd2diR1m1NF0uQC52ODDN MnjPNlI{OzZ{NE[=
HBC5 M{e0bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEP2OngxNjBzLUGwNEDPxE1? NFnFbm81QCCq MVXMc4chT0l3ME2tO{45PyCP M1PaTlIzOzN4MkS2
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MDA-MB-231 M{\xU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLWNE4xOS1zMECg{txO MnfhOFghcA>? MXjMc4chT0l3ME2tPE4xQSCP MWKyNlM{PjJ2Nh?=
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SF268 M1G3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{L1NVAvODFvMUCwJO69VQ>? MUC0PEBp MnHsUI9oKEeLNUC9MVcvQTJiTR?= NGW1eJUzOjN|NkK0Oi=>
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DMS114 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFmyUIUxNjBzLUGwNEDPxE1? MlfXOFghcA>? MofNUI9oKEeLNUC9MVgvOzliTR?= MkXSNlI{OzZ{NE[=
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Trypanosoma brucei brucei NXvVS3M2TnWwY4Tpc44hSXO|YYm= MUOyNFAhdk1? NXW0fnZwOTJiaB?= M4jGbmROW09? NF7zVYFF\WO{ZXHz[UBqdiCyaH;zdIhwfGmmeXygbY5we2m2b3ygdIhwe3CqYYTlJIxmfmWu NXnmb3F5OjR6MEW5OFY>
Trypanosoma brucei brucei M{LHXmZ2dmO2aX;uJGF{e2G7 NInlTJkyQCCq NVv5N3VnTE2VTx?= M3voXmlvcGmkaYTpc44hd2ZicnXj[ZB1d3JvbXXkbYF1\WRiZX7kc4N6fG:|aYOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5idILhcpNn\XK{aX6geZB1[Wun MVeyOFgxPTl2Nh?=
Trypanosoma brucei brucei NI\vWHpHfW6ldHnvckBCe3OjeR?= MVOyNFAhdk1? Mn3HNVIhcA>? NYTrSXF1TE2VTx?= NGH5WoxG\m[nY4Sgc44he3CqaX7nc416dGWrbjDs[ZZmdA>? NVzOW4I2OjR6MEW5OFY>
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SBC-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojJTWM2OD15NEKgdG0> MUnTRW5ITVJ?
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NCI-H720 NIPOWIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XGVGlEPTB;Mz61O{BvVQ>? NFjVTFVUSU6JRWK=
BFTC-909 NY\MV2hvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDLNlVKSzVyPUOuO|Ehdk1? MWjTRW5ITVJ?
BPH-1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDzdZVKSzVyPUSuO|Yhdk1? NIK0W4FUSU6JRWK=
PC-3 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVr5XmtoUUN3ME21MlA6KG6P M3LKNnNCVkeHUh?=
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KP-4 M3;4OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPmXnFKSzVyPUegcm0> M4HVO3NCVkeHUh?=
LU-139 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jKUWlEPTB;Nz63O{BvVQ>? MlPTV2FPT0WU
ETK-1 NXXmd21vT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXO1TZZGUUN3ME23Mlg5KG6P Mon5V2FPT0WU
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MHH-PREB-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{O3SmlEPTB;OT6xNkBvVQ>? NVT2O244W0GQR1XS
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NCI-H1666 MnXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEflNFVKSzVyPUmuO|Ehdk1? Ml;nV2FPT0WU
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H4 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXnJR|UxRTF{Lk[3JI5O MlnBV2FPT0WU
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GCT NVnXO2ZYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWD5U4ZCUUN3ME2xN{43QCCwTR?= MoXtV2FPT0WU
EoL-1 M3\qdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTlTWM2OD1zMz65N{BvVQ>? MWDTRW5ITVJ?
LB2241-RCC M1jJW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTF2LkCxJI5O MV7TRW5ITVJ?
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CHL-1 NHHIUnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\NdZplUUN3ME2xOU41PSCwTR?= MXfTRW5ITVJ?
VMRC-RCZ M1jpN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7QTWM2OD1zNT62N{BvVQ>? NUnnfJFuW0GQR1XS
HH M2nYfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLMTWM2OD1zNT63JI5O NH;hdGdUSU6JRWK=
NUGC-3 MkP6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWGxU5lOUUN3ME2xOk4{PCCwTR?= Ml7lV2FPT0WU
EGI-1 MoLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3aRXlKSzVyPUG2MlQ{KG6P NEP5N5pUSU6JRWK=
OS-RC-2 MkDOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXHJR|UxRTF4LkS3JI5O M1rhenNCVkeHUh?=
MOLT-16 M{ThRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnL2TWM2OD1zNz6xOUBvVQ>? M16wV3NCVkeHUh?=
NCI-H209 NHn2VoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPNTWM2OD1zNz6yPUBvVQ>? MVPTRW5ITVJ?
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KYSE-180 Mm\wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH;1SVhKSzVyPUS2MlE4KG6P Mo\2V2FPT0WU
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BT-474 NF\yR5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFW4bZlKSzVyPUKzOU44OyCwTR?= Mo[5V2FPT0WU
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HT-1197 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTJ|OD6wPUBvVQ>? M3HQOXNCVkeHUh?=
CAL-54 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPYUmpbUUN3ME2yN|gvPDlibl2= MVTTRW5ITVJ?
NB10 NH7oUpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jGW2lEPTB;MkSwMlA3KG6P M1nRd3NCVkeHUh?=
PANC-10-05 NIXoc3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;Vd2tYUUN3ME2yOFUvPTZibl2= MWTTRW5ITVJ?
NCI-H522 NGTOTGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fKOWlEPTB;MkS4MlMyKG6P NYL3S|Q2W0GQR1XS
A388 MnTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1jiO2lEPTB;MkS5MlgzKG6P MVXTRW5ITVJ?
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KLE NY[5TJd1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEL3dnNKSzVyPUK1NU45PyCwTR?= NYjocYdsW0GQR1XS
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NCI-H810 MlLKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFPPR3dKSzVyPUK3PE4{OSCwTR?= NFzNXGJUSU6JRWK=
LB771-HNC NGnhVFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HWW2lEPTB;Mki1Mlg1KG6P MofIV2FPT0WU
LCLC-103H NXjuUpdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGC4fINKSzVyPUK4OU46QSCwTR?= NFrQSGFUSU6JRWK=
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CAL-72 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn74TWM2OD1{OUOuNVkhdk1? MkWwV2FPT0WU
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ChaGo-K-1 MlTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4naWWlEPTB;M{K4MlEhdk1? NVj3fIZCW0GQR1XS
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DJM-1 NEXRVIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTN2MD6zN{BvVQ>? Mlv4V2FPT0WU
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NCI-H1651 NVf4ZVBVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTN2ND6xPEBvVQ>? M{\rcXNCVkeHUh?=
COLO-792 NFvtOphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXu2OoJvUUN3ME2zOVQvPDJibl2= MnHzV2FPT0WU
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TH-3 NEHOT5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfLd3BKSzVyPUO3PU46PSCwTR?= MYLTRW5ITVJ?
HT-1376 M{nyZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTN6ND64PEBvVQ>? MWHTRW5ITVJ?
RH-18 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWH0[2ZqUUN3ME2zPVQvPzRibl2= NULsUZJ5W0GQR1XS
NB6 NXLVSYV6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTN7Nj62OkBvVQ>? M1K0[XNCVkeHUh?=
COLO-320-HSR NVL4RnVDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1X0fWlEPTB;NECzMlM4KG6P M1X3cXNCVkeHUh?=
UACC-893 MnjpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlGwTWM2OD12ME[uOFchdk1? NYnMR2VqW0GQR1XS
DSH1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzpTWM2OD12ME[uPVEhdk1? MkSyV2FPT0WU
TE-10 Mn7SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoD4TWM2OD12MEeuNFEhdk1? MXvTRW5ITVJ?
HCC70 M1LQRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGT5eolKSzVyPUSwPU4zOSCwTR?= NGi2blBUSU6JRWK=
TGBC11TKB M{D1V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4XJe2lEPTB;NEGwMlM{KG6P NV\5SGwzW0GQR1XS
NCI-H727 NVP6[pp6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTRzMj6xNUBvVQ>? MX7TRW5ITVJ?
ALL-PO MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrOTWM2OD12MUWuOlkhdk1? M{[zUHNCVkeHUh?=
ABC-1 M3PWO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXqfYlKSzVyPUSyNE41PSCwTR?= MnrvV2FPT0WU
NCI-H69 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NITEbWJKSzVyPUSyOk44PiCwTR?= MnGyV2FPT0WU
GP5d MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;OTZFHUUN3ME20N|QvPDFibl2= NGezV|FUSU6JRWK=
UMC-11 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTR3OD6zOkBvVQ>? M{\3V3NCVkeHUh?=
RMG-I NF36cIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHDV3lJUUN3ME20OlcvPTZibl2= NWjWPWxnW0GQR1XS
YAPC NVfrcVh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTR7MD62JI5O Mn3wV2FPT0WU
LS-1034 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUPJR|UxRTR7MT6wOkBvVQ>? NWDwVWNKW0GQR1XS
RCM-1 NImxV2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTR7Nj62PEBvVQ>? NF3MWJdUSU6JRWK=
HCC1954 MnraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW[5bGlVUUN3ME21NVIvPSCwTR?= MkDZV2FPT0WU
SK-MEL-24 M1Pq[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\NTWM2OD13MU[uOVEhdk1? MkDiV2FPT0WU
NB12 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTjeoxjUUN3ME21NlgvPDJibl2= M4nYNXNCVkeHUh?=
SW756 M2\XV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTV3ND65OkBvVQ>? NIrvXZJUSU6JRWK=
HCC1187 NWnobHZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTV5NT64N{BvVQ>? NHrBTmlUSU6JRWK=
NCI-H2342 M4XpeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTV7MD6zPUBvVQ>? NFvvXG9USU6JRWK=
NCI-H2291 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTV7OD6zNUBvVQ>? NXnI[XBDW0GQR1XS
OVCAR-3 MljpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvNTWM2OD13OUiuPVYhdk1? M{[yU3NCVkeHUh?=
MHH-NB-11 M{\MSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XRSGlEPTB;NkK5MlAyKG6P NIL0VotUSU6JRWK=
SAS M1:2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XFU2lEPTB;NkWyMlY4KG6P M1\0OHNCVkeHUh?=
COLO-824 NFK1Z3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonMTWM2OD14OEmuN|chdk1? NGH1fldUSU6JRWK=
HCC1395 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLiXGpCUUN3ME22PVgvPSCwTR?= NUHSeopKW0GQR1XS
COLO-668 M1XG[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTdyNj6xJI5O MYnTRW5ITVJ?
NCI-H226 MnXMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M161c2lEPTB;N{C3Mlghdk1? NW\h[m44W0GQR1XS
NB17 NFLj[o5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIq0d|ZKSzVyPUeyNU44PSCwTR?= NIHsOFhUSU6JRWK=
SW1463 NGXi[oNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTd|OT6xPUBvVQ>? NHH4O5dUSU6JRWK=
TGW MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfrTWM2OD15NkCuNVUhdk1? NEHjV3FUSU6JRWK=
NCI-H526 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTLb4F1UUN3ME24NlMvPTNibl2= Mk\2V2FPT0WU
COR-L88 M3nrOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn2wTWM2OD16NEiuNVIhdk1? MojBV2FPT0WU
NCI-H441 MonQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTh7NT6yNkBvVQ>? NGj3Vo9USU6JRWK=
NCI-H630 NUHENJJOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnGc4lOUUN3ME25NVIvQTZibl2= NEDsOmZUSU6JRWK=
Mo-T MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmW0TWM2OD17NEeuPFghdk1? NXzMVoMyW0GQR1XS
JAR MknYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvzVXk3UUN3ME25OVYvOjRibl2= M3zo[3NCVkeHUh?=
NCI-H1838 Mlm2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTFwMEKzPFgh|ryP M{XHeHNCVkeHUh?=
DoTc2-4510 NI\JbXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI[xfY1KSzVyPUGuNFc{PzZizszN MVLTRW5ITVJ?
MKN28 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vvTWlEPTB;MT6wPVAzPCEQvF2= MYfTRW5ITVJ?
HuP-T3 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mli0TWM2OD1zLkGxPVA2KM7:TR?= NHqxWJBUSU6JRWK=
TE-9 NFTVT4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlH3TWM2OD1zLkGyPVc{KM7:TR?= MmLkV2FPT0WU
NY MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjDbZhKSzVyPUGuNVY4QTJizszN NGH1[VNUSU6JRWK=
HT55 MlznS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn:wTWM2OD1zLkOxN|Q1KM7:TR?= MnPyV2FPT0WU
SW837 M1POS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PaN2lEPTB;MT6zNlk4QCEQvF2= NFXUOGlUSU6JRWK=
NCI-H2029 NEC4Wo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPsTWM2OD1zLkSxO|kyKM7:TR?= NHTHeHlUSU6JRWK=
IST-SL1 NFznZ2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTuTWM2OD1zLkS0NlQh|ryP NHjjWGJUSU6JRWK=
COLO-741 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrJTWM2OD1zLkS5O|cyKM7:TR?= MWPTRW5ITVJ?
LU-65 M1PzOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvDO|ROUUN3ME2xMlYzOjR7IN88US=> NEPEO2hUSU6JRWK=
NCI-H1304 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3yzemlEPTB;MT62OVQ6QCEQvF2= MlHZV2FPT0WU
KARPAS-299 MlnsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTtNG1YUUN3ME2xMlc6PDd7IN88US=> M1q3XHNCVkeHUh?=
NCI-H358 M{XnNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTFwOUW1NFMh|ryP NGrmWFZUSU6JRWK=
OAW-28 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTJwME[5NVkh|ryP MnPRV2FPT0WU
C8166 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnJ[XZZUUN3ME2yMlY{Ozl{IN88US=> NU\oRVY3W0GQR1XS
COLO-678 M2XTWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjMZZZKSzVyPUKuPFM4PjhizszN Ml7qV2FPT0WU
SK-N-DZ MojqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3:3XmlEPTB;Mj64OlM5OSEQvF2= NX:4OmZOW0GQR1XS
NCI-H82 M1PxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrSW3hKSzVyPUKuPVA{PjlizszN MofFV2FPT0WU
JVM-2 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HmSGlEPTB;Mz6wN|E5QCEQvF2= MWXTRW5ITVJ?
SW1116 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\kTWM2OD1|LkC1OFEyKM7:TR?= MnLuV2FPT0WU
MDA-MB-453 NWTuZ4R2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVfJR|UxRTNwMUC0N|kh|ryP NF:4[|lUSU6JRWK=
Calu-6 M4Oz[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofsTWM2OD1|LkG5PVch|ryP M{jjWHNCVkeHUh?=
SHP-77 M4DyOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NULmN5g2UUN3ME2zMlUzQCEQvF2= NIf2NZpUSU6JRWK=
Capan-2 NV7zS3dlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYnJR|UxRTRwM{K1PFEh|ryP MXrTRW5ITVJ?
SW948 MonTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XZNmlEPTB;ND63OFc4QSEQvF2= M{m5ZnNCVkeHUh?=
HDLM-2 NVrlT2hZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTVwMEe3NlUh|ryP MlrFV2FPT0WU
LAN-6 NF3VPG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnLRnVKSzVyPU[uNlE1QTVizszN MoTLV2FPT0WU
LU-135 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlfNTWM2OD14LkSzNFc4KM7:TR?= MojiV2FPT0WU
T84 M365UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorNTWM2OD14Lkm4OlQh|ryP NEXWc4ZUSU6JRWK=
CAPAN-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIXRTXlKSzVyPUeuOlIzOzNizszN M3TXe3NCVkeHUh?=
SW1417 MnX3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXvJR|UxRTdwOUG3N|Eh|ryP MlvJV2FPT0WU
BALL-1 NVzGO41FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRThwNUC0NFkh|ryP NYTGd45wW0GQR1XS
HT-29 MnznS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXPTWM2OD17LkC3OVk6KM7:TR?= MWrTRW5ITVJ?
C3A M2PYRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4n1T2lEPTB;OT64PFM6PCEQvF2= MmXjV2FPT0WU
NCI-H1993 NUnie2FHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnVTWM2OD1zMD61NFgyKM7:TR?= NFzzRVdUSU6JRWK=
SK-MEL-1 NVfpS2RmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYDJR|UxRTFzLk[yPFkh|ryP NIj2cG9USU6JRWK=
DU-145 NFro[IxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLlNWhKSzVyPUG0MlUxPTJizszN MonJV2FPT0WU
KP-N-YN MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTF2LkWxNFMh|ryP NIfsUYZUSU6JRWK=
CCRF-CEM NFzUO29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvMTWM2OD1zND63PFA6KM7:TR?= MXPTRW5ITVJ?
ZR-75-30 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTF4LkOzNFMh|ryP NXXGboVbW0GQR1XS
A673 NVrLOGZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTJyLkW1NFch|ryP NIPmW4lUSU6JRWK=
K-562 NFPiZXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\MTWM2OD1{OD60NVg{KM7:TR?= MkPJV2FPT0WU

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験
特集

プロトコル (参考用のみ)

キナーゼアッセイ:

[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.

細胞アッセイ:

[2]

細胞株 HCT116, DLD-1 and SW480 cells
濃度 0-1 μM
反応時間 48 hours
実験の流れ

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.

動物実験:

[1]

動物モデル Female Harlan athymic nude mice
製剤 NMP/polyethylene glycol 300 (10/90, v/v)
投薬量 45 mg/kg
投与方法 p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download BEZ235 (NVP-BEZ235, Dactolisib) SDF
分子量 469.55
化学式

C30H23N5O

CAS No. 915019-65-7
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMF 18 mg/mL warming (38.33 mM)
DMSO 0.01 mg/mL (0.02 mM)
<1 mg/mL (<1 mM)
In vivo NMP+polyethylene glycol 300 (10+90, v+v) 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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.
化学名 2-methyl-2-(4-(3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile

カスタマーフィードバック (8)


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Source Cancer Res, 2010, 70, 4982-4994. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Detection of lipid kinase activities of PI3K p110α mutants
Cell Lines HEK293T cells
Concentrations
Incubation Time
Results "Evaluation of relative kinase activity of these mutants revealed that mutant P449T exhibited gain of function (>2-fold) compared with wild-type PI3K α (Fig. A). With regard to two hotspot mutants (E545K and H1047R), we examined the effect of NVP-BEZ235 and other PI3K inhibitors on their enzymatic activity and found no striking difference in their efficacies compared with wild-type p110α (Fig. B).

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Source Clin Cancer Res, 2010, 16, 6029-6039. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Synergism studies, Immunoblot assays, Clonogenic assays
Cell Lines Melanoma cell
Concentrations 0.1-100 μM
Incubation Time 1-24 h
Results One of the proposed mechanisms of resistance to PI3KIs is mutation in the Ras-Raf pathway, which are found in more than half of melanomas. By ANOVA, no association was found between the IC50 values of NVP-BEZ235 and the presence or absence of B-Raf mutations (Fig. A). The targets of NVP-BEZ235, pAkt and pP70S6K, were both decreased with exposure to the drug in a time- and dose-dependent fashion, as shown in Figure B for YUVON and YUSIK cell lines. Clonogenicity was studied in YUVON and YUSIK cells with exposure to the dual PI3K/mTOR inhibitor. As shown in Figure C, NVP-BEZ235 effectively inhibits clonogenicity at low nanomolar concentrations.

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Source Breast Cancer Res , 2011, 13, R52. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Immunofluorescence staining
Cell Lines MCF7 cells, IGF1R cells
Concentrations
Incubation Time
Results We investigated the effect of IGF-1 stimulation on MCF7/IGF-1R 4-OH-TAM resistance in a structurally and physiologically relevant context by use of a modified 3D culture. Both parental MCF7 (Figure a) and MCF7/IGF-1R cells (Figure b) were responsive to E2 or IGF-1 by forming acini on Matrigel, but the response was significantly larger in MCF7/IGF-1R cells with altered a cinar morphogenesis. inhibition of IGF -1R/ERK/Akt signaling by respective kinase inhibitors restored 4-OH-TAM sensitivity of MCF7/IGF-1R cells in 3D culture (Figure c).

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Source Breast Cancer Res, 2011, 13:R52. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Western blot, A sulforhodamine B ( SRB) colorimetric assay
Cell Lines MCF7 cells, GF-1R cells
Concentrations 0.01-10 μM
Incubation Time
Results IGF-1-stimulated proliferation was drastically restrained by BEZ235 at either 1 or 10 μM (Figure a).While IGF-1R and ERK signaling remained unaffected in response to IGF-1, the phosphorylation level of Akt was diminished with an increase in the dose of BEZ235, largely at 0.1 μM and entirely at 0.5 μM (Figure b). Likewise, the cell proliferation rate decreased correspondingly to Akt phosphorylation levels, significantly dropping at 0.1μM BEZ235 (Figure c)

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Source Eur J Cancer, 2010, 46, 1111-1121. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method LanthaScreen assay
Cell Lines JFCR39 cell lines
Concentrations 0.016 μM
Incubation Time
Results As shown in Fig. A, NVP-BEZ235 and other inhibitors all inhibited mTOR in a dose-dependent manner. The IC50 values were calculated and are shown in Fig. B. NVP-BEZ235 inhibited mTOR potently, with IC50 value of 0.002 μM. In contrast, ZSTK474, GDC-0941 and LY294002 weakly inhibited mTOR, with IC50 values of 0.377, 0.413 and 3.86μM, respectively. To further demonstrate their selectivity for class I PI3K, the IC50 values of these inhibitors for mTOR were divided by their corresponding IC50s for class I PI3Ka, and the resulting ratios were plotted in Fig. C. Clearly, ZSTK474 and GDC-0941 revealed much higher selectivity for inhibiting class I PI3K than the other two inhibitors. In contrast, NVP-BEZ235 more potently inhibited the activity of mTOR than that of class I PI3K

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Source Dr. Zhang of Tianjin Medical University. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Western blot
Cell Lines breast cancer cells
Concentrations 0-10 nM
Incubation Time 3 h
Results

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Rating
Source Dr. Zhang of Tianjin Medical University. BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Western blot
Cell Lines breast cancer cells
Concentrations 0-50 nM
Incubation Time 3 h
Results

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Source BEZ235 (NVP-BEZ235, Dactolisib) purchased from Selleck
Method Western Blotting
Cell Lines xenografts
Concentrations
Incubation Time
Results Phospholipase A2 group 4A (PLA2G4A) expression was increased after BEZ235 treatment in basal-like xenografts.

文献中の引用 (81)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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