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 MoDhRY51cW2rY4LvZolidCCDc4PhfS=> M2m0OlE5KGh? NIG3NFhFVVOR NUn5fGhHSW62aYTyfZBidm:|b33hcEBi[3Srdnn0fUB4cXSqIFXDOVAhd2ZiMD6wNFI2KM7:TR?= M17xTlI1QDB3OUS2
MCF7 M{HQNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXfDPJRoOC5yMT2xNFAh|ryP M3K2fFQ5KGh? M2PGfmROW09? NILTUoRKSzVyPUCuO|Mh|ryP MnzxNlM5PzF7MES=
HCT116 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYOwMlAyNTFyMDFOwG0> MVG0PEBp MmTRSG1UVw>? MUDJR|UxRTFwMU[g{txO MXyyN|g4OTlyNB?=
U87MG NXLm[lhkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\aTGIxNjBzLUGwNEDPxE1? NWf6NpBEPDhiaB?= NWfrV|VlTE2VTx?= NVvKc4dMUUN3ME2xMlMzKM7:TR?= NYXVb4Y3OjN6N{G5NFQ>
HBC4 M3TXcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlz0NE4xOS1zMECg{txO M{\wc|Q5KGh? MnfsUI9oKEeLNUC9MVgvPjFiTR?= MWOyNlM{PjJ2Nh?=
BSY1 M4rqVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUewMlAyNTFyMDFOwG0> NEXuTlg1QCCq MnflUI9oKEeLNUC9MVgvPDhiTR?= NYDOblRPOjJ|M{[yOFY>
HBC5 NF7uR5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTsNE4xOS1zMECg{txO NIDXcIY1QCCq NUXx[Fk4VG:pIFfJOVA:NTdwOEegUS=> NFHhdIMzOjN|NkK0Oi=>
MCF7 NUXZRpk1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWToZVY3OC5yMT2xNFAh|ryP MoXUOFghcA>? NWC3blF5VG:pIFfJOVA:NThwMU[gUS=> MXyyNlM{PjJ2Nh?=
MDA-MB-231 NFXqd3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17acFAvODFvMUCwJO69VQ>? MmS4OFghcA>? NWLP[3lqVG:pIFfJOVA:NThwMEmgUS=> M1HFblIzOzN4MkS2
U251 NUHCPIZIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfFNE4xOS1zMECg{txO MXi0PEBp NXfFcJo3VG:pIFfJOVA:NTdwNk[gUS=> M4KySVIzOzN4MkS2
SF268 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiwMlAyNTFyMDFOwG0> Ml3HOFghcA>? MlH2UI9oKEeLNUC9MVcvQTJiTR?= NH73dYIzOjN|NkK0Oi=>
SF295 M2X1fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWCwMlAyNTFyMDFOwG0> MV[0PEBp NWLqbVB{VG:pIFfJOVA:NThwM{GgUS=> MoDuNlI{OzZ{NE[=
SF539 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\WNE4xOS1zMECg{txO M{\tWFQ5KGh? MmrUUI9oKEeLNUC9MVgvPTliTR?= MXeyNlM{PjJ2Nh?=
SNB75 M1nGO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHre|AxNjBzLUGwNEDPxE1? MXS0PEBp MYTMc4chT0l3ME2tPE42QCCP MXqyNlM{PjJ2Nh?=
SNB78 NYnFOlV{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnhcFlLOC5yMT2xNFAh|ryP NYfSRXJuPDhiaB?= M2TLN2xw\yCJSUWwQU05NjZ3IF2= MojXNlI{OzZ{NE[=
HCC2998 NUTS[GhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLuNE4xOS1zMECg{txO NVvGSG82PDhiaB?= MYPMc4chT0l3ME2tPE4xPSCP MUCyNlM{PjJ2Nh?=
KM12 NEfMdY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHn4fYgxNjBzLUGwNEDPxE1? NIDMelc1QCCq NILDU2RNd2diR1m1NF0uPy53NDDN NILV[nIzOjN|NkK0Oi=>
HT-29 M1;TcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\oXFFJOC5yMT2xNFAh|ryP MWW0PEBp NGHxOFJNd2diR1m1NF0uPy55NTDN NGPwcWkzOjN|NkK0Oi=>
HCT15 NGDoTFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4\JcVAvODFvMUCwJO69VQ>? NG\NRXg1QCCq MVfMc4chT0l3ME2tPE4xOyCP M4mzRVIzOzN4MkS2
HCT116 Ml;tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zJXVAvODFvMUCwJO69VQ>? NGTWfVI1QCCq M2\i[mxw\yCJSUWwQU04NjZzIF2= NVS0fXZnOjJ|M{[yOFY>
NCI-H23 M4C5TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHmwNW4xNjBzLUGwNEDPxE1? NIPkclU1QCCq MUnMc4chT0l3ME2tO{43PCCP NUfZNIFmOjJ|M{[yOFY>
NCI-H226 M{TaVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHO5NWExNjBzLUGwNEDPxE1? NYHIV3B{PDhiaB?= M2fmU2xw\yCJSUWwQU05NjR2IF2= NXnIcJZxOjJ|M{[yOFY>
NCI-H522 NILHW2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH[y[XgxNjBzLUGwNEDPxE1? MmnVOFghcA>? NFnKWGpNd2diR1m1NF0uQC52NTDN MnXRNlI{OzZ{NE[=
NCI-H438 NYP4TW9WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXCXJAxNjBzLUGwNEDPxE1? M2DSWFQ5KGh? M{j0dWxw\yCJSUWwQU05NjFzIF2= MoCwNlI{OzZ{NE[=
A549 M3zDfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkH4NE4xOS1zMECg{txO NVnYSlRDPDhiaB?= NHzJRndNd2diR1m1NF0uQC5yNzDN NWKyWXFmOjJ|M{[yOFY>
DMS273 M33NNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYCwMlAyNTFyMDFOwG0> NF7GWWM1QCCq NVO2bW1zVG:pIFfJOVA:NTdwOECgUS=> M2SzclIzOzN4MkS2
DMS114 M{nvOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELuSXkxNjBzLUGwNEDPxE1? NIW5O4I1QCCq MUXMc4chT0l3ME2tPE4{QSCP MnTqNlI{OzZ{NE[=
LOXIMVI NVLlfWR4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX[wMlAyNTFyMDFOwG0> NI[1cWE1QCCq NIDFO|BNd2diR1m1NF0uQC54NjDN MnvBNlI{OzZ{NE[=
OVCAR3 NWfoVYFET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DCWlAvODFvMUCwJO69VQ>? MnnmOFghcA>? NFG0NIpNd2diR1m1NF0uQC5zNzDN NIH6OWszOjN|NkK0Oi=>
OVCAR4 M2fVZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;RSlAvODFvMUCwJO69VQ>? NYTsXHZVPDhiaB?= MX\Mc4chT0l3ME2tPE42QCCP M17wNVIzOzN4MkS2
OVCAR5 NHfiPGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLpTmgxNjBzLUGwNEDPxE1? MVm0PEBp NVfoVYJwVG:pIFfJOVA:NTdwNUegUS=> NGnqUIgzOjN|NkK0Oi=>
OVCAR8 NI[5fVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnXWFAxNjBzLUGwNEDPxE1? MoiyOFghcA>? MXrMc4chT0l3ME2tO{45PCCP M4nkdlIzOzN4MkS2
SKOV3 MmXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPjfVNCOC5yMT2xNFAh|ryP NILoV2w1QCCq NUjMZ5NSVG:pIFfJOVA:NThwNEGgUS=> MXmyNlM{PjJ2Nh?=
RXF631L NWLpdnVJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1L2bVAvODFvMUCwJO69VQ>? NIryd2I1QCCq NVXoUmxXVG:pIFfJOVA:NThwMkGgUS=> NIjMdIszOjN|NkK0Oi=>
ACHN MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfXNE4xOS1zMECg{txO NEe5[XY1QCCq NY\FeHVCVG:pIFfJOVA:NTdwOUWgUS=> Mm\UNlI{OzZ{NE[=
St-4 MlXFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPafVAxNjBzLUGwNEDPxE1? M33RWVQ5KGh? MWPMc4chT0l3ME2tO{41PyCP M13GR|IzOzN4MkS2
MKN1 NYrsd4RCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXztZ49zOC5yMT2xNFAh|ryP NWjGU5RJPDhiaB?= NXruV3V5VG:pIFfJOVA:NThwNEGgUS=> NHLoO5QzOjN|NkK0Oi=>
MKN7 M3q5U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWOwMlAyNTFyMDFOwG0> MlnlOFghcA>? NYn4UXhXVG:pIFfJOVA:NTdwNkigUS=> NWjuPVJUOjJ|M{[yOFY>
MKN28 NX7ySXBCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY[wMlAyNTFyMDFOwG0> M1PvWVQ5KGh? MXPMc4chT0l3ME2tO{4xPyCP NVWwdYJwOjJ|M{[yOFY>
MKN45 NEXkflJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfHPZQxNjBzLUGwNEDPxE1? M4PTflQ5KGh? NIrrdohNd2diR1m1NF0uQC5|NDDN M3f5dVIzOzN4MkS2
MKN74 NG\pWlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MViwMlAyNTFyMDFOwG0> MXi0PEBp MVjMc4chT0l3ME2tO{41OiCP NHjyNmszOjN|NkK0Oi=>
DU145 NHT4OFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY[wMlAyNTFyMDFOwG0> NYTkR|duPDhiaB?= MUnMc4chT0l3ME2tPE4yPiCP NXjGPZFjOjJ|M{[yOFY>
PC3 NIS1WIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX72fnliOC5yMT2xNFAh|ryP NF;2ZZc1QCCq M1y4eWxw\yCJSUWwQU05NjZ4IF2= NYTXbIIyOjJ|M{[yOFY>
Trypanosoma brucei brucei MWLGeY5kfGmxbjDBd5NigQ>? MnnUNlAxKG6P M{DhT|EzKGh? MUjEUXNQ NUKwZlhrTGWlcnXhd4UhcW5icHjvd5Bpd3SrZInsJIlvd3OrdH;sJJBpd3OyaHH0[UBt\X[nbB?= NHvibVYzPDhyNUm0Oi=>
Trypanosoma brucei brucei MYLGeY5kfGmxbjDBd5NigQ>? MXqxPEBp MWrEUXNQ M2T2V2lvcGmkaYTpc44hd2ZicnXj[ZB1d3JvbXXkbYF1\WRiZX7kc4N6fG:|aYOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5idILhcpNn\XK{aX6geZB1[Wun MXqyOFgxPTl2Nh?=
Trypanosoma brucei brucei NEnyRXZHfW6ldHnvckBCe3OjeR?= M13NfFIxOCCwTR?= M4jqWlEzKGh? NHrIbWRFVVOR NIfaWm5G\m[nY4Sgc44he3CqaX7nc416dGWrbjDs[ZZmdA>? NWPkSGoyOjR6MEW5OFY>
Trypanosoma brucei brucei MYrGeY5kfGmxbjDBd5NigQ>? MVOyNFAhdk1? M{DuOlEzKGh? NHPuSmZFVVOR MYfF[oZm[3Rib36gdIhwe3CqYYTp[Jlt[2ixbHnu[UBt\X[nbB?= NUPnNHkzOjR6MEW5OFY>
UM-UC-3 Mm\HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFX4[GJKSzVyPUOxOUBxVQ>? M3iwV3NCVkeHUh?=
SBC-1 NH7zPWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTd2MjDwUS=> M3GzPHNCVkeHUh?=
MKN1 NGKyblBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvyTWM2OD1{Lkigcm0> Mn3zV2FPT0WU
NCI-H720 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXaRlJxUUN3ME2zMlU4KG6P MlTHV2FPT0WU
BFTC-909 MlvCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TU[2lEPTB;Mz63NUBvVQ>? NHLOfW9USU6JRWK=
BPH-1 M{e5bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{L4[GlEPTB;ND63OkBvVQ>? NH;EfnZUSU6JRWK=
PC-3 M2XBWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGjIfXpKSzVyPUWuNFkhdk1? M1PHcXNCVkeHUh?=
AN3-CA NH7hcYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTVwNU[gcm0> MnPZV2FPT0WU
HN NXzxT5RmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\JTWM2OD13Lkm2JI5O M3nEV3NCVkeHUh?=
HCC2218 M4Cx[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fLSGlEPTB;Nj62NUBvVQ>? NVzvb4dvW0GQR1XS
KP-4 NUnU[Fg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnVUWJKSzVyPUegcm0> NUPHPXpMW0GQR1XS
LU-139 NY\DdGZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlyzTWM2OD15Lke3JI5O M2OwNHNCVkeHUh?=
ETK-1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTdwOEigcm0> NUPWOHl2W0GQR1XS
Ramos-2G6-4C10 M4DLeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnwZYZKSzVyPUiuOFkhdk1? MlvMV2FPT0WU
MHH-PREB-1 MmG1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\V[41KSzVyPUmuNVIhdk1? MVTTRW5ITVJ?
DU-4475 MoHzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRTlwNESgcm0> NX7I[|hzW0GQR1XS
NCI-H1666 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTlwN{Ggcm0> M{XGSnNCVkeHUh?=
CAMA-1 NW[3Oo9iT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHjTWM2OD17Lkigcm0> MXrTRW5ITVJ?
TYK-nu M1vMeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvH[XZXUUN3ME25Mlk1KG6P M3y3b3NCVkeHUh?=
MFE-280 NWPzdmp5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\UTWlEPTB;OT65PUBvVQ>? NYLlV4djW0GQR1XS
A549 NULVfnZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3TTWM2OD1zMD6xOEBvVQ>? NIDWd3lUSU6JRWK=
769-P NVS5SW95T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIK3fXNKSzVyPUGwMlQ1KG6P MVrTRW5ITVJ?
L-363 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2n4NmlEPTB;MUCuOlkhdk1? NIjwV4JUSU6JRWK=
ES8 M{Lsd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVv4[G04UUN3ME2xNE46KG6P Mnz4V2FPT0WU
PA-1 Mm\RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13MNmlEPTB;MUGuPFIhdk1? NWXhOXFYW0GQR1XS
Mewo MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XMPWlEPTB;MUGuPVkhdk1? NUPPVXcxW0GQR1XS
HSC-3 NH3wNINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTKWHBKSzVyPUGyMlIyKG6P NYrsXFdpW0GQR1XS
H4 NEDESFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFj3XFJKSzVyPUGyMlY4KG6P MWfTRW5ITVJ?
BB65-RCC M{f3bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTF{LkeyJI5O MlTEV2FPT0WU
NCI-H1793 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nwNGlEPTB;MUKuPFIhdk1? MX\TRW5ITVJ?
KARPAS-45 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTF|LkWxJI5O NXT5XFVYW0GQR1XS
GCT M4jZN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrPXpFKSzVyPUGzMlY5KG6P M3;PUHNCVkeHUh?=
EoL-1 NUfQfoZDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTF|LkmzJI5O NH:5[ZZUSU6JRWK=
LB2241-RCC NFnJc3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3nZZZKSzVyPUG0MlAyKG6P MoW4V2FPT0WU
ES5 NX71fYl1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFLhdXFKSzVyPUG0Mlc1KG6P MV3TRW5ITVJ?
LOXIMVI MkewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTDPGN[UUN3ME2xOE46QSCwTR?= NUTORm5xW0GQR1XS
COR-L105 NUfObVBFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTF3LkC0JI5O MnnBV2FPT0WU
P12-ICHIKAWA MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTF3LkGgcm0> M3i0OXNCVkeHUh?=
CHL-1 M4XVVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXfXbFk1UUN3ME2xOU41PSCwTR?= NYWxdnN{W0GQR1XS
VMRC-RCZ NFzSO|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvxe3M3UUN3ME2xOU43OyCwTR?= MY\TRW5ITVJ?
HH MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYH1SWdOUUN3ME2xOU44KG6P M{fFOXNCVkeHUh?=
NUGC-3 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTF4LkO0JI5O NIS0U3NUSU6JRWK=
EGI-1 M4[wZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TDdWlEPTB;MU[uOFMhdk1? MkT0V2FPT0WU
OS-RC-2 M{LkfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnHVTWM2OD1zNj60O{BvVQ>? NYTRNGJSW0GQR1XS
MOLT-16 NFzyWlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\rRmJKSzVyPUG3MlE2KG6P MlLMV2FPT0WU
NCI-H209 MlHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlPiTWM2OD1zNz6yPUBvVQ>? MlrnV2FPT0WU
697 NHe1THhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XLfmlEPTB;MUeuOFMhdk1? NXXLT|l1W0GQR1XS
D-56MG M2XPXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGm1fpdKSzVyPUG3MlY6KG6P MW\TRW5ITVJ?
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NCI-H358 NX7kcoV3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TDRWlEPTB;MT65OVUxOyEQvF2= MofCV2FPT0WU
OAW-28 MkTYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M17iWWlEPTB;Mj6wOlkyQSEQvF2= M13BVXNCVkeHUh?=
C8166 Ml\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTJwNkOzPVIh|ryP NYj6fVRNW0GQR1XS
COLO-678 M2PKZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLScJFKSzVyPUKuPFM4PjhizszN MnPMV2FPT0WU
SK-N-DZ MnT4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjjSJViUUN3ME2yMlg3OzhzIN88US=> NGnZR2tUSU6JRWK=
NCI-H82 MlTVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDmTWM2OD1{LkmwN|Y6KM7:TR?= NFXGbmdUSU6JRWK=
JVM-2 NULkTHRNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTNwMEOxPFgh|ryP NEnabm1USU6JRWK=
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Calu-6 M3XvVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLweWZKSzVyPUOuNVk6PyEQvF2= MWrTRW5ITVJ?
SHP-77 NED3OZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTNwNUK4JO69VQ>? MYPTRW5ITVJ?
Capan-2 MoPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\OZmlEPTB;ND6zNlU5OSEQvF2= MlPOV2FPT0WU
SW948 MmfrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTsTWM2OD12Lke0O|c6KM7:TR?= NUjCdllHW0GQR1XS
HDLM-2 NUj5cWwzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrLTWM2OD13LkC3O|I2KM7:TR?= M{e3OHNCVkeHUh?=
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CAPAN-1 MmftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3TsS2lEPTB;Nz62NlI{OyEQvF2= MVrTRW5ITVJ?
SW1417 M3vMemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmmyTWM2OD15LkmxO|MyKM7:TR?= NYP5XFV2W0GQR1XS
BALL-1 NILDRXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{GxN2lEPTB;OD61NFQxQSEQvF2= M{PLVHNCVkeHUh?=
HT-29 NVr0Z4c6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPQ[5l2UUN3ME25MlA4PTl7IN88US=> MWHTRW5ITVJ?
C3A NGXidZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVHY[FV3UUN3ME25Mlg5Ozl2IN88US=> MmnDV2FPT0WU
NCI-H1993 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\5XmlEPTB;MUCuOVA5OSEQvF2= NI\uTGxUSU6JRWK=
SK-MEL-1 NYDEWnMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYnJR|UxRTFzLk[yPFkh|ryP MmXpV2FPT0WU
DU-145 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXsTWM2OD1zND61NFUzKM7:TR?= MnPOV2FPT0WU
KP-N-YN NV7ROm1FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWfJR|UxRTF2LkWxNFMh|ryP MVzTRW5ITVJ?
CCRF-CEM NV[0VVJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;Lfm5KSzVyPUG0Mlc5ODlizszN NVLtSYtlW0GQR1XS
ZR-75-30 NGjxVG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTF4LkOzNFMh|ryP M4XvcHNCVkeHUh?=
A673 MnKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTJyLkW1NFch|ryP MWfTRW5ITVJ?
K-562 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPYTWM2OD1{OD60NVg{KM7:TR?= M1vRPHNCVkeHUh?=

... 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)

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.

技術サポート&よくある質問(FAQ)

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Related PI3K 阻害剤

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  • Wortmannin

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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