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 M17ufWFvfGmvaXPyc4Jq[WxiQYPzZZk> NYLqOJBVOThiaB?= NFj0WZVFVVOR NXPZW4hCSW62aYTyfZBidm:|b33hcEBi[3Srdnn0fUB4cXSqIFXDOVAhd2ZiMD6wNFI2KM7:TR?= MmTDNlQ5ODV7NE[=
MCF7 NHLvc2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTtNE4xOS1zMECg{txO Mn22OFghcA>? MmTXSG1UVw>? MoT2TWM2OD1yLkezJO69VQ>? NFTFdW0zOzh5MUmwOC=>
HCT116 NIXaRVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXCNXkxNjBzLUGwNEDPxE1? NXm4PYVRPDhiaB?= MX\EUXNQ M{LIVGlEPTB;MT6xOkDPxE1? M4PqZVI{QDdzOUC0
U87MG NYKyb2x2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mli3NE4xOS1zMECg{txO MkS4OFghcA>? M3;FNWROW09? MoraTWM2OD1zLkOyJO69VQ>? NWLm[VRJOjN6N{G5NFQ>
HBC4 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVHwbVhiOC5yMT2xNFAh|ryP MWS0PEBp MYPMc4chT0l3ME2tPE43OSCP M4K1dVIzOzN4MkS2
BSY1 M3\Lc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{HVOFAvODFvMUCwJO69VQ>? M4[wO|Q5KGh? M{\YZmxw\yCJSUWwQU05NjR6IF2= M{XwOFIzOzN4MkS2
HBC5 MnvhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TMWlAvODFvMUCwJO69VQ>? MXy0PEBp M4XiWmxw\yCJSUWwQU04Njh5IF2= NHrGV5QzOjN|NkK0Oi=>
MCF7 NWX4VI1FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\C[nkxNjBzLUGwNEDPxE1? NVnIVoZRPDhiaB?= NY\abHY4VG:pIFfJOVA:NThwMU[gUS=> MWSyNlM{PjJ2Nh?=
MDA-MB-231 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLCNE4xOS1zMECg{txO MWm0PEBp M1nqd2xw\yCJSUWwQU05NjB7IF2= NYH4V5ZzOjJ|M{[yOFY>
U251 NYC2VFZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml7BNE4xOS1zMECg{txO NXnGVXRQPDhiaB?= NWnydFk6VG:pIFfJOVA:NTdwNk[gUS=> Ml;xNlI{OzZ{NE[=
SF268 MojwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUGwMlAyNTFyMDFOwG0> NITN[HY1QCCq Mm\qUI9oKEeLNUC9MVcvQTJiTR?= Mli1NlI{OzZ{NE[=
SF295 MlP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3L5XFAvODFvMUCwJO69VQ>? MnqyOFghcA>? NFrRc|dNd2diR1m1NF0uQC5|MTDN MoCyNlI{OzZ{NE[=
SF539 M13hTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLiNE4xOS1zMECg{txO MXm0PEBp MUPMc4chT0l3ME2tPE42QSCP M1qx[VIzOzN4MkS2
SNB75 MoTYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLnT3AxNjBzLUGwNEDPxE1? MUe0PEBp MXTMc4chT0l3ME2tPE42QCCP MV:yNlM{PjJ2Nh?=
SNB78 NX3NPXJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3HPWlAvODFvMUCwJO69VQ>? M3K5flQ5KGh? NET3R|ZNd2diR1m1NF0uQC54NTDN NV7FS3lVOjJ|M{[yOFY>
HCC2998 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M36wdlAvODFvMUCwJO69VQ>? MlfOOFghcA>? MoXuUI9oKEeLNUC9MVgvODViTR?= NHvFcnYzOjN|NkK0Oi=>
KM12 M4LHU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPTelhoOC5yMT2xNFAh|ryP MX:0PEBp Mnu1UI9oKEeLNUC9MVcvPTRiTR?= MUiyNlM{PjJ2Nh?=
HT-29 NXTJWZk1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoK1NE4xOS1zMECg{txO M1Xje|Q5KGh? M4fhUWxw\yCJSUWwQU04Njd3IF2= M{[y[lIzOzN4MkS2
HCT15 M1XJcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1jpVlAvODFvMUCwJO69VQ>? M2TFSFQ5KGh? NVnJRWVrVG:pIFfJOVA:NThwMEOgUS=> NV7GNpJnOjJ|M{[yOFY>
HCT116 MnXBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTiZmIxNjBzLUGwNEDPxE1? M2XFT|Q5KGh? MnfrUI9oKEeLNUC9MVcvPjFiTR?= MYOyNlM{PjJ2Nh?=
NCI-H23 NV3nOZJvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHPRWt6OC5yMT2xNFAh|ryP MUC0PEBp MVrMc4chT0l3ME2tO{43PCCP NXr4TGZEOjJ|M{[yOFY>
NCI-H226 NWK0R20{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITYbmoxNjBzLUGwNEDPxE1? NI\z[o41QCCq Mn7xUI9oKEeLNUC9MVgvPDRiTR?= NU\rWWJzOjJ|M{[yOFY>
NCI-H522 M1XNUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TXNVAvODFvMUCwJO69VQ>? M4WxTVQ5KGh? NFK0d2xNd2diR1m1NF0uQC52NTDN NGnPT4QzOjN|NkK0Oi=>
NCI-H438 MoPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXSNE4xOS1zMECg{txO NH;vVZU1QCCq MkLCUI9oKEeLNUC9MVgvOTFiTR?= NYHjR4hqOjJ|M{[yOFY>
A549 MkXoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHzZWExNjBzLUGwNEDPxE1? NUjWephvPDhiaB?= MnjPUI9oKEeLNUC9MVgvODdiTR?= NWCy[Zc6OjJ|M{[yOFY>
DMS273 MofxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnBZZYxNjBzLUGwNEDPxE1? NXPxO2ZMPDhiaB?= NYG1bWk5VG:pIFfJOVA:NTdwOECgUS=> NH;wZ|czOjN|NkK0Oi=>
DMS114 NYDKdVAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY[wMlAyNTFyMDFOwG0> MmfTOFghcA>? NFjBPGJNd2diR1m1NF0uQC5|OTDN NH;NXFUzOjN|NkK0Oi=>
LOXIMVI NXzXfGlDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{TuelAvODFvMUCwJO69VQ>? NX\MXnMyPDhiaB?= NITmU3NNd2diR1m1NF0uQC54NjDN Mlf6NlI{OzZ{NE[=
OVCAR3 M4KxT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHEUHltOC5yMT2xNFAh|ryP M{DFbFQ5KGh? M4Lrb2xw\yCJSUWwQU05NjF5IF2= NYmxeZAxOjJ|M{[yOFY>
OVCAR4 MlnDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXj[oRmOC5yMT2xNFAh|ryP NFzkbow1QCCq NGHSTmhNd2diR1m1NF0uQC53ODDN MXWyNlM{PjJ2Nh?=
OVCAR5 M{jk[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXuxeIpbOC5yMT2xNFAh|ryP M4XOPFQ5KGh? MljlUI9oKEeLNUC9MVcvPTdiTR?= M2TxSFIzOzN4MkS2
OVCAR8 Ml20S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mkm2NE4xOS1zMECg{txO MVW0PEBp MlvpUI9oKEeLNUC9MVcvQDRiTR?= M3u2eFIzOzN4MkS2
SKOV3 M4T2[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mly3NE4xOS1zMECg{txO NX75NHdOPDhiaB?= M4XvSmxw\yCJSUWwQU05NjRzIF2= MYSyNlM{PjJ2Nh?=
RXF631L Ml\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3q4SFAvODFvMUCwJO69VQ>? Mke5OFghcA>? M1e5Nmxw\yCJSUWwQU05NjJzIF2= NXTkS4VGOjJ|M{[yOFY>
ACHN MmW5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmGyNE4xOS1zMECg{txO NYDhboxpPDhiaB?= M{XhOGxw\yCJSUWwQU04Njl3IF2= NY\LUVN6OjJ|M{[yOFY>
St-4 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo[1NE4xOS1zMECg{txO M3:4PFQ5KGh? MWjMc4chT0l3ME2tO{41PyCP NUizW4VyOjJ|M{[yOFY>
MKN1 MmjUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3i0d|AvODFvMUCwJO69VQ>? NEXuV|g1QCCq NYX0cHZ[VG:pIFfJOVA:NThwNEGgUS=> MX[yNlM{PjJ2Nh?=
MKN7 M1XQSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2wMlAyNTFyMDFOwG0> MnjSOFghcA>? NHnpN4RNd2diR1m1NF0uPy54ODDN NEXBO|kzOjN|NkK0Oi=>
MKN28 MlPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkjWNE4xOS1zMECg{txO MXe0PEBp MX;Mc4chT0l3ME2tO{4xPyCP NE[y[WYzOjN|NkK0Oi=>
MKN45 MmjDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWP4fGl7OC5yMT2xNFAh|ryP Mni4OFghcA>? NXvVVXRtVG:pIFfJOVA:NThwM{SgUS=> MUGyNlM{PjJ2Nh?=
MKN74 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnS3NE4xOS1zMECg{txO M3fOUVQ5KGh? M4\XTmxw\yCJSUWwQU04NjR{IF2= NXvRVXhmOjJ|M{[yOFY>
DU145 MoDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jLN|AvODFvMUCwJO69VQ>? NFrKVYo1QCCq NHLVNZFNd2diR1m1NF0uQC5zNjDN NEnWUoYzOjN|NkK0Oi=>
PC3 NIO0epJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVewMlAyNTFyMDFOwG0> MWS0PEBp NGD5[mtNd2diR1m1NF0uQC54NjDN MoPVNlI{OzZ{NE[=
Trypanosoma brucei brucei MULGeY5kfGmxbjDBd5NigQ>? NIjqWnIzODBibl2= NX[5SGV7OTJiaB?= MV3EUXNQ M4OzcWRm[3KnYYPlJIlvKHCqb4PwbI91cWS7bDDpco9{cXSxbDDwbI9{eGijdHWgcIV3\Wx? Mn35NlQ5ODV7NE[=
Trypanosoma brucei brucei NHnrbnlHfW6ldHnvckBCe3OjeR?= MnrlNVghcA>? M3T6b2ROW09? NUTieWVUUW6qaXLpeIlwdiCxZjDy[YNmeHSxcj3t[YRq[XSnZDDlcoRw[3m2b4Ppd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjD0doFve2[ncoLpckB2eHSja3W= NYPIdpBlOjR6MEW5OFY>
Trypanosoma brucei brucei MYfGeY5kfGmxbjDBd5NigQ>? NU\pUpduOjByIH7N NHTqRo4yOiCq M3HweWROW09? NIDmNmtG\m[nY4Sgc44he3CqaX7nc416dGWrbjDs[ZZmdA>? MVyyOFgxPTl2Nh?=
Trypanosoma brucei brucei MWLGeY5kfGmxbjDBd5NigQ>? MW[yNFAhdk1? MlvzNVIhcA>? Mnf2SG1UVw>? NEHKVWdG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> NW\lOnk4OjR6MEW5OFY>
UM-UC-3 M1jneGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTNzNTDwUS=> M2LFTHNCVkeHUh?=
SBC-1 NGrj[nhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{W4bmlEPTB;N{SyJJBO NH7GW3RUSU6JRWK=
MKN1 NEjxNHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrkTlVCUUN3ME2yMlghdk1? MXnTRW5ITVJ?
NCI-H720 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTNwNUegcm0> M3j6UnNCVkeHUh?=
BFTC-909 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTNwN{Ggcm0> MYjTRW5ITVJ?
BPH-1 NIS2N3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETZbphKSzVyPUSuO|Yhdk1? M1;vPXNCVkeHUh?=
PC-3 MnLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGH1e3pKSzVyPUWuNFkhdk1? NXy4U5RjW0GQR1XS
AN3-CA MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTVwNU[gcm0> MlzhV2FPT0WU
HN M3XOZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\4U2lEPTB;NT65OkBvVQ>? MnrkV2FPT0WU
HCC2218 M4LWRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7pNYhlUUN3ME22MlYyKG6P NFfRV3pUSU6JRWK=
KP-4 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETT[2lKSzVyPUegcm0> NHX2e5RUSU6JRWK=
LU-139 NHfxd2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\iZmlEPTB;Nz63O{BvVQ>? NXvTe3JJW0GQR1XS
ETK-1 NXXsSIJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXHTWM2OD15Lki4JI5O NVWyVnpXW0GQR1XS
Ramos-2G6-4C10 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEWwNFRKSzVyPUiuOFkhdk1? MVLTRW5ITVJ?
MHH-PREB-1 Mnf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrTTWM2OD17LkGyJI5O MWfTRW5ITVJ?
DU-4475 NHXab2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXPJR|UxRTlwNESgcm0> M2nE[3NCVkeHUh?=
NCI-H1666 M3Gzd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWLBUXBnUUN3ME25MlcyKG6P M4rUdnNCVkeHUh?=
CAMA-1 NI\mOlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvuXJhKSzVyPUmuPEBvVQ>? Mk\UV2FPT0WU
TYK-nu NU\SWnplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{LpUWlEPTB;OT65OEBvVQ>? NITRVYxUSU6JRWK=
MFE-280 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\NTWM2OD17Lkm5JI5O MX;TRW5ITVJ?
A549 NV[yNXg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPvTWM2OD1zMD6xOEBvVQ>? NWm0RWFzW0GQR1XS
769-P MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTFyLkS0JI5O MmfwV2FPT0WU
L-363 NVGwfVU5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmHQTWM2OD1zMD62PUBvVQ>? NFPOVHdUSU6JRWK=
ES8 M4D3PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDIUZUyUUN3ME2xNE46KG6P MWTTRW5ITVJ?
PA-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;ZPWlEPTB;MUGuPFIhdk1? NU[yT|E4W0GQR1XS
Mewo MnqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3PnPWlEPTB;MUGuPVkhdk1? NGPGVGlUSU6JRWK=
HSC-3 Mn;qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4S1emlEPTB;MUKuNlEhdk1? NEnCNVhUSU6JRWK=
H4 M4HBOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4[4d2lEPTB;MUKuOlchdk1? MkjFV2FPT0WU
BB65-RCC NX7QZ2NbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\UcZpKSzVyPUGyMlczKG6P MWrTRW5ITVJ?
NCI-H1793 M2X4dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPVVZUyUUN3ME2xNk45OiCwTR?= MUjTRW5ITVJ?
KARPAS-45 M{DReWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo[3TWM2OD1zMz61NUBvVQ>? NULjXGw2W0GQR1XS
GCT M4nseGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWe0Z21EUUN3ME2xN{43QCCwTR?= MWDTRW5ITVJ?
EoL-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfLRlFKSzVyPUGzMlk{KG6P NEDQOFhUSU6JRWK=
LB2241-RCC MkjUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2rle2lEPTB;MUSuNFEhdk1? NWr2TmliW0GQR1XS
ES5 MlfES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTidXRUUUN3ME2xOE44PCCwTR?= MnXyV2FPT0WU
LOXIMVI M{fDfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2n2VmlEPTB;MUSuPVkhdk1? Mn3sV2FPT0WU
COR-L105 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUD3RnIzUUN3ME2xOU4xPCCwTR?= NYjCOldUW0GQR1XS
P12-ICHIKAWA MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HWcWlEPTB;MUWuNUBvVQ>? NVS3fW1bW0GQR1XS
CHL-1 NHfZe|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEi4[JZKSzVyPUG1MlQ2KG6P NVHjU|FzW0GQR1XS
VMRC-RCZ M2PISWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTF3Lk[zJI5O MYXTRW5ITVJ?
HH M1jsT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVS4TXpOUUN3ME2xOU44KG6P M1fHPHNCVkeHUh?=
NUGC-3 NUL0WlAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjURpZKSzVyPUG2MlM1KG6P NIfZfFlUSU6JRWK=
EGI-1 M1vwS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTF4LkSzJI5O MlzCV2FPT0WU
OS-RC-2 M{[1Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn\OTWM2OD1zNj60O{BvVQ>? M2XnZnNCVkeHUh?=
MOLT-16 NEHZNZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIDtRVBKSzVyPUG3MlE2KG6P NFH4R|VUSU6JRWK=
NCI-H209 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fD[WlEPTB;MUeuNlkhdk1? MlHoV2FPT0WU
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HCE-4 Mn3aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnL4TWM2OD1{NkKuOUBvVQ>? M1;mVnNCVkeHUh?=
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DJM-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfsTWM2OD1|NECuN|Mhdk1? NWfvVmhTW0GQR1XS
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COLO-792 M1jsRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTN3ND60NkBvVQ>? M2\lXHNCVkeHUh?=
ACHN MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGC0co1KSzVyPUO1Ok44OSCwTR?= NV\x[YV{W0GQR1XS
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HT-1376 NHzh[oJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTN6ND64PEBvVQ>? MYHTRW5ITVJ?
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COLO-320-HSR MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfnTWM2OD12MEOuN|chdk1? M4jOXXNCVkeHUh?=
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TE-10 Mn\qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1H0bGlEPTB;NEC3MlAyKG6P M2r6ZXNCVkeHUh?=
HCC70 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\YTWM2OD12MEmuNlEhdk1? NYiz[XU3W0GQR1XS
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NCI-H727 MonpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{DXOWlEPTB;NEGyMlEyKG6P MmDnV2FPT0WU
ALL-PO MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXmyenRZUUN3ME20NVUvPjlibl2= NHTy[mJUSU6JRWK=
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YAPC MnywS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnuzTWM2OD12OUCuOkBvVQ>? MVXTRW5ITVJ?
LS-1034 M{DhSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13LS2lEPTB;NEmxMlA3KG6P MYfTRW5ITVJ?
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HCC1954 MnX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3vTWM2OD13MUKuOUBvVQ>? NIHBXGxUSU6JRWK=
SK-MEL-24 NGHQOGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\aTWM2OD13MU[uOVEhdk1? M1m3THNCVkeHUh?=
NB12 M1e0N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfofJJKSzVyPUWyPE41OiCwTR?= NHX5PZVUSU6JRWK=
SW756 NYXlcndxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjRe2t5UUN3ME21OVQvQTZibl2= MULTRW5ITVJ?
HCC1187 NInTdohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF;mOolKSzVyPUW3OU45OyCwTR?= MoK5V2FPT0WU
NCI-H2342 NX;GTJA2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\N[FlCUUN3ME21PVAvOzlibl2= NXH3coVpW0GQR1XS
NCI-H2291 NH3mdlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTV7OD6zNUBvVQ>? MXrTRW5ITVJ?
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MHH-NB-11 NGq5cJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIC2TWhKSzVyPU[yPU4xOSCwTR?= MXTTRW5ITVJ?
SAS NVXXR5E5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrLfZlzUUN3ME22OVIvPjdibl2= NEfKWHFUSU6JRWK=
COLO-824 NHvje|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnQbJR6UUN3ME22PFkvOzdibl2= NU\HdYN5W0GQR1XS
HCC1395 NIHCeIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mkn5TWM2OD14OUiuOUBvVQ>? NW\pdJBGW0GQR1XS
COLO-668 NYrrcFNtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;pTWM2OD15ME[uNUBvVQ>? NGrTbZFUSU6JRWK=
NCI-H226 M{jxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfvOYRNUUN3ME23NFcvQCCwTR?= MmXoV2FPT0WU
NB17 M3u4bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTd{MT63OUBvVQ>? M3zz[nNCVkeHUh?=
SW1463 NVfIcG55T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTiVnBnUUN3ME23N|kvOTlibl2= NFfwSZZUSU6JRWK=
TGW NX3wXoxLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHDclE3UUN3ME23OlAvOTVibl2= MmfiV2FPT0WU
NCI-H526 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYGxNY5VUUN3ME24NlMvPTNibl2= NIfTd5BUSU6JRWK=
COR-L88 Ml33S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljiTWM2OD16NEiuNVIhdk1? MmPoV2FPT0WU
NCI-H441 M4\FT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXzeo5KSzVyPUi5OU4zOiCwTR?= MV7TRW5ITVJ?
NCI-H630 M1nLcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\HTWM2OD17MUKuPVYhdk1? NELhNZBUSU6JRWK=
Mo-T MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nqU2lEPTB;OUS3Mlg5KG6P MWrTRW5ITVJ?
JAR NI\ZXlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTl3Nj6yOEBvVQ>? Ml\zV2FPT0WU
NCI-H1838 NVHpUFhLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvLTWM2OD1zLkCyN|g5KM7:TR?= M3;zbHNCVkeHUh?=
DoTc2-4510 M4LaTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TmeGlEPTB;MT6wO|M4PiEQvF2= NU\xeJVEW0GQR1XS
MKN28 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHj2OW5KSzVyPUGuNFkxOjRizszN NUjVZoZwW0GQR1XS
HuP-T3 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI[xVZVKSzVyPUGuNVE6ODVizszN MoTyV2FPT0WU
TE-9 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7hd3hHUUN3ME2xMlEzQTd|IN88US=> NVq0UWN1W0GQR1XS
NY NYjXbmxHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NETJSlBKSzVyPUGuNVY4QTJizszN MVXTRW5ITVJ?
HT55 Mk\hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmDZTWM2OD1zLkOxN|Q1KM7:TR?= M17FUXNCVkeHUh?=
SW837 NXyzbJpxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHRTWM2OD1zLkOyPVc5KM7:TR?= M3nYRnNCVkeHUh?=
NCI-H2029 M{nYZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnOU5lEUUN3ME2xMlQyPzlzIN88US=> NH3n[|VUSU6JRWK=
IST-SL1 M3HhXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmriTWM2OD1zLkS0NlQh|ryP MYLTRW5ITVJ?
COLO-741 NWfXXWZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zlV2lEPTB;MT60PVc4OSEQvF2= MYLTRW5ITVJ?
LU-65 NIDDR5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3X6N2lEPTB;MT62NlI1QSEQvF2= NX3aXllHW0GQR1XS
NCI-H1304 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYXzOmtEUUN3ME2xMlY2PDl6IN88US=> MkLCV2FPT0WU
KARPAS-299 NHq4elVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{j5eGlEPTB;MT63PVQ4QSEQvF2= NGe0VIlUSU6JRWK=
NCI-H358 M2LFSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXTZpFwUUN3ME2xMlk2PTB|IN88US=> NGr6fpdUSU6JRWK=
OAW-28 Mkn0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHDOm5KSzVyPUKuNFY6OTlizszN M2PrXHNCVkeHUh?=
C8166 NH31XYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXoTWM2OD1{Lk[zN|kzKM7:TR?= NIfJPXlUSU6JRWK=
COLO-678 MkO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDPTWM2OD1{LkizO|Y5KM7:TR?= NEfCfnlUSU6JRWK=
SK-N-DZ NEHme4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTJwOE[zPFEh|ryP NIDPendUSU6JRWK=
NCI-H82 NHXJbpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{L6b2lEPTB;Mj65NFM3QSEQvF2= MX\TRW5ITVJ?
JVM-2 M1X1b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmi4TWM2OD1|LkCzNVg5KM7:TR?= MWTTRW5ITVJ?
SW1116 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkfETWM2OD1|LkC1OFEyKM7:TR?= MXzTRW5ITVJ?
MDA-MB-453 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTNwMUC0N|kh|ryP NHu3NWZUSU6JRWK=
Calu-6 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV3JR|UxRTNwMUm5O{DPxE1? NYDE[HFVW0GQR1XS
SHP-77 MmnTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofETWM2OD1|LkWyPEDPxE1? MV\TRW5ITVJ?
Capan-2 NF\yV3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnSyTWM2OD12LkOyOVgyKM7:TR?= MkjkV2FPT0WU
SW948 MnTnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoixTWM2OD12Lke0O|c6KM7:TR?= M4XwenNCVkeHUh?=
HDLM-2 MmHvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmLFTWM2OD13LkC3O|I2KM7:TR?= M2DKUHNCVkeHUh?=
LAN-6 NVf4R2gxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVPN[nJmUUN3ME22MlIyPDl3IN88US=> M4O1SHNCVkeHUh?=
LU-135 M3nTcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDlSGlKSzVyPU[uOFMxPzdizszN NEPOPHVUSU6JRWK=
T84 NXXkXGJ7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTZwOUi2OEDPxE1? M3XPNXNCVkeHUh?=
CAPAN-1 NX25ZXlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXjVGxKSzVyPUeuOlIzOzNizszN NFvISlNUSU6JRWK=
SW1417 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofTTWM2OD15LkmxO|MyKM7:TR?= Mmm2V2FPT0WU
BALL-1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPnTWM2OD16LkWwOFA6KM7:TR?= NVPwU5E2W0GQR1XS
HT-29 NEXQRXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn7jTWM2OD17LkC3OVk6KM7:TR?= Mm\nV2FPT0WU
C3A NHrzbFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnGfFJKSzVyPUmuPFg{QTRizszN M4fyTXNCVkeHUh?=
NCI-H1993 M4\vUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYC3Zo04UUN3ME2xNE42ODhzIN88US=> NEXaRWVUSU6JRWK=
SK-MEL-1 M1[yO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nFSWlEPTB;MUGuOlI5QSEQvF2= Mlj3V2FPT0WU
DU-145 M{DKWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUSyOlBnUUN3ME2xOE42ODV{IN88US=> MmXTV2FPT0WU
KP-N-YN NE\6XWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTF2LkWxNFMh|ryP M3LBOXNCVkeHUh?=
CCRF-CEM M4HLRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M173TWlEPTB;MUSuO|gxQSEQvF2= Mnz0V2FPT0WU
ZR-75-30 NVr3TWhOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmDyTWM2OD1zNj6zN|A{KM7:TR?= MYDTRW5ITVJ?
A673 NVnme3N4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PwOmlEPTB;MkCuOVUxPyEQvF2= NVTPPZk2W0GQR1XS
K-562 NUPvPJhpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHKTWM2OD1{OD60NVg{KM7:TR?= NXX5cpczW0GQR1XS

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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 warmed (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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