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 MXzBcpRqdWmlcn;ibYFtKEG|c3H5 MUSxPEBp MlXJSG1UVw>? M4X1bmFvfGm2conwZY5we2:vYXygZYN1cX[rdImge4l1cCCHQ{WwJI9nKDBwMECyOUDPxE1? NIHyUYgzPDhyNUm0Oi=>
MCF7 NFn6SppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\2elAvODFvMUCwJO69VQ>? M3y3R|Q5KGh? MVPEUXNQ M3qwXWlEPTB;MD63N{DPxE1? MlziNlM5PzF7MES=
HCT116 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\2SZdxOC5yMT2xNFAh|ryP NXXiepdwPDhiaB?= MmK1SG1UVw>? M{LlcWlEPTB;MT6xOkDPxE1? M2G1elI{QDdzOUC0
U87MG MojzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rTVVAvODFvMUCwJO69VQ>? MYO0PEBp NHrzRWhFVVOR MkPxTWM2OD1zLkOyJO69VQ>? MV2yN|g4OTlyNB?=
HBC4 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorMNE4xOS1zMECg{txO Mnq3OFghcA>? NFjsbIJNd2diR1m1NF0uQC54MTDN NVWw[XlYOjJ|M{[yOFY>
BSY1 MnzrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXe3TodIOC5yMT2xNFAh|ryP M1\wPVQ5KGh? M{OyeWxw\yCJSUWwQU05NjR6IF2= M1K0SVIzOzN4MkS2
HBC5 NXXOboo5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEDudHMxNjBzLUGwNEDPxE1? NFLONoM1QCCq M{HrVmxw\yCJSUWwQU04Njh5IF2= NWqxeI1LOjJ|M{[yOFY>
MCF7 NYPqcYR6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3FT5M{OC5yMT2xNFAh|ryP MX[0PEBp MVXMc4chT0l3ME2tPE4yPiCP MWCyNlM{PjJ2Nh?=
MDA-MB-231 NVHlZYp[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TWOVAvODFvMUCwJO69VQ>? NHq3OWE1QCCq MWjMc4chT0l3ME2tPE4xQSCP NWmz[ZZEOjJ|M{[yOFY>
U251 NVzzRlBpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFPC[FMxNjBzLUGwNEDPxE1? MleyOFghcA>? NYnuZnJKVG:pIFfJOVA:NTdwNk[gUS=> MYSyNlM{PjJ2Nh?=
SF268 NFHOc5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYm2SFJROC5yMT2xNFAh|ryP NFLESnI1QCCq MVHMc4chT0l3ME2tO{46OiCP MVuyNlM{PjJ2Nh?=
SF295 NYq4W|Z2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrYNE4xOS1zMECg{txO MorkOFghcA>? NUjJV5U{VG:pIFfJOVA:NThwM{GgUS=> NX;5WVZSOjJ|M{[yOFY>
SF539 NIrsZYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2n6V|AvODFvMUCwJO69VQ>? MX20PEBp MUfMc4chT0l3ME2tPE42QSCP NHLOcIIzOjN|NkK0Oi=>
SNB75 NVLSSFNRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHDRld[OC5yMT2xNFAh|ryP MXS0PEBp NF7HO4FNd2diR1m1NF0uQC53ODDN MVeyNlM{PjJ2Nh?=
SNB78 M1mwVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{PhbFAvODFvMUCwJO69VQ>? NUHCZ|JSPDhiaB?= M2rDcWxw\yCJSUWwQU05NjZ3IF2= NY[yXYh2OjJ|M{[yOFY>
HCC2998 MlT4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUDubYpnOC5yMT2xNFAh|ryP NXXOSXJrPDhiaB?= NFXobZpNd2diR1m1NF0uQC5yNTDN MYOyNlM{PjJ2Nh?=
KM12 MlW4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFf3OXIxNjBzLUGwNEDPxE1? NXjNd49GPDhiaB?= M{\FXGxw\yCJSUWwQU04NjV2IF2= M2HySlIzOzN4MkS2
HT-29 M17jbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;pOZBjOC5yMT2xNFAh|ryP MoXiOFghcA>? MVnMc4chT0l3ME2tO{44PSCP NGLmPWEzOjN|NkK0Oi=>
HCT15 MlS2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjZNE4xOS1zMECg{txO MXi0PEBp NFPSXHRNd2diR1m1NF0uQC5yMzDN NIexZoMzOjN|NkK0Oi=>
HCT116 M{TqNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYKwMlAyNTFyMDFOwG0> M33DUlQ5KGh? MV\Mc4chT0l3ME2tO{43OSCP NGDWW5IzOjN|NkK0Oi=>
NCI-H23 NVTJeJhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHBb5RbOC5yMT2xNFAh|ryP NELhWXI1QCCq MkTJUI9oKEeLNUC9MVcvPjRiTR?= MlzINlI{OzZ{NE[=
NCI-H226 NFm5bpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4rvUFAvODFvMUCwJO69VQ>? NHu1eXk1QCCq NIrBTpNNd2diR1m1NF0uQC52NDDN NHvQbFczOjN|NkK0Oi=>
NCI-H522 MmDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TJ[FAvODFvMUCwJO69VQ>? NGDYUYU1QCCq NXHuTot[VG:pIFfJOVA:NThwNEWgUS=> NYTYXIxGOjJ|M{[yOFY>
NCI-H438 M17O[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU[wMlAyNTFyMDFOwG0> MUC0PEBp NV3xc3VIVG:pIFfJOVA:NThwMUGgUS=> M3ToS|IzOzN4MkS2
A549 MojTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHTRnYxNjBzLUGwNEDPxE1? MnLSOFghcA>? NEHRR|dNd2diR1m1NF0uQC5yNzDN NH\HN2IzOjN|NkK0Oi=>
DMS273 NEXSVm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rPblAvODFvMUCwJO69VQ>? NFvNcZU1QCCq NGK2Z49Nd2diR1m1NF0uPy56MDDN M2jITlIzOzN4MkS2
DMS114 NULvbW1GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4exZlAvODFvMUCwJO69VQ>? M1HQOVQ5KGh? M1;6d2xw\yCJSUWwQU05NjN7IF2= NYC0e3NlOjJ|M{[yOFY>
LOXIMVI MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\TNE4xOS1zMECg{txO MX:0PEBp NV;Ie49kVG:pIFfJOVA:NThwNk[gUS=> MUOyNlM{PjJ2Nh?=
OVCAR3 M3nZT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTGd3FTOC5yMT2xNFAh|ryP NF;KUmU1QCCq MojYUI9oKEeLNUC9MVgvOTdiTR?= NFnlfWYzOjN|NkK0Oi=>
OVCAR4 NI\qTYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4TUZ|AvODFvMUCwJO69VQ>? NXfkXHk2PDhiaB?= M2TyOmxw\yCJSUWwQU05NjV6IF2= MnvZNlI{OzZ{NE[=
OVCAR5 Mn23S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2e3clAvODFvMUCwJO69VQ>? MmWxOFghcA>? MnXHUI9oKEeLNUC9MVcvPTdiTR?= M{PndVIzOzN4MkS2
OVCAR8 NVfRbJFqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\ZUm5TOC5yMT2xNFAh|ryP MUm0PEBp MnOwUI9oKEeLNUC9MVcvQDRiTR?= NXHBOok4OjJ|M{[yOFY>
SKOV3 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETQTFYxNjBzLUGwNEDPxE1? M1HQflQ5KGh? MWTMc4chT0l3ME2tPE41OSCP NIjaVnQzOjN|NkK0Oi=>
RXF631L M1LnVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMlAyNTFyMDFOwG0> MlPiOFghcA>? MXnMc4chT0l3ME2tPE4zOSCP M161T|IzOzN4MkS2
ACHN MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnL4NE4xOS1zMECg{txO MWe0PEBp NGP0NlFNd2diR1m1NF0uPy57NTDN NETTZoEzOjN|NkK0Oi=>
St-4 MmPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;pNoMxNjBzLUGwNEDPxE1? MV20PEBp M3TIVmxw\yCJSUWwQU04NjR5IF2= M3TONVIzOzN4MkS2
MKN1 MnrxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU[wMlAyNTFyMDFOwG0> MnXuOFghcA>? MWfMc4chT0l3ME2tPE41OSCP M4qzT|IzOzN4MkS2
MKN7 MlWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4mze|AvODFvMUCwJO69VQ>? MmC3OFghcA>? NFnwWGdNd2diR1m1NF0uPy54ODDN M4\wXVIzOzN4MkS2
MKN28 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2j0UVAvODFvMUCwJO69VQ>? MnLNOFghcA>? M4\0ZWxw\yCJSUWwQU04NjB5IF2= M{fVSlIzOzN4MkS2
MKN45 NE\iOXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DBT|AvODFvMUCwJO69VQ>? NVzKW2h{PDhiaB?= NFLRSZhNd2diR1m1NF0uQC5|NDDN MUCyNlM{PjJ2Nh?=
MKN74 NF;tPGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\3UoZEOC5yMT2xNFAh|ryP MUO0PEBp MnXEUI9oKEeLNUC9MVcvPDJiTR?= NFjwTJMzOjN|NkK0Oi=>
DU145 NELWZYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVywMlAyNTFyMDFOwG0> MWq0PEBp M2i4RWxw\yCJSUWwQU05NjF4IF2= MVuyNlM{PjJ2Nh?=
PC3 NWXvZ3E1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFTFPIQxNjBzLUGwNEDPxE1? NIPiTIQ1QCCq NHrU[GFNd2diR1m1NF0uQC54NjDN M{PaXlIzOzN4MkS2
Trypanosoma brucei brucei NYLGfoRwTnWwY4Tpc44hSXO|YYm= MWiyNFAhdk1? NWexdVNoOTJiaB?= NX:yWI9ETE2VTx?= Mn:xSIVkemWjc3WgbY4heGixc4Doc5Rq\HmuIHnuc5NqfG:uIIDoc5NxcGG2ZTDs[ZZmdA>? M4jsXVI1QDB3OUS2
Trypanosoma brucei brucei NWqxbZJbTnWwY4Tpc44hSXO|YYm= M3HEUlE5KGh? MlT0SG1UVw>? MlXlTY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? NEDMZXYzPDhyNUm0Oi=>
Trypanosoma brucei brucei M2PoSWZ2dmO2aX;uJGF{e2G7 MknJNlAxKG6P MWixNkBp MU\EUXNQ NX;nelh7TW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? MYqyOFgxPTl2Nh?=
Trypanosoma brucei brucei M3KyZmZ2dmO2aX;uJGF{e2G7 MlLNNlAxKG6P M{DZU|EzKGh? Mly4SG1UVw>? NF34[YlG\m[nY4Sgc44heGixc4DoZZRq\HmuY3jvcIlv\SCuZY\lcC=> M3SzZ|I1QDB3OUS2
UM-UC-3 NFX2WphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHrBVphKSzVyPUOxOUBxVQ>? NWnuTW5pW0GQR1XS
SBC-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3SdW9KSzVyPUe0NkBxVQ>? NFnk[|BUSU6JRWK=
MKN1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTJwODDuUS=> NF\5RnZUSU6JRWK=
NCI-H720 NYjSR|RuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rq[2lEPTB;Mz61O{BvVQ>? MYTTRW5ITVJ?
BFTC-909 MlPKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGnqSWZKSzVyPUOuO|Ehdk1? MWLTRW5ITVJ?
BPH-1 MmO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUm1SXh{UUN3ME20Mlc3KG6P MnjYV2FPT0WU
PC-3 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnJR|UxRTVwMEmgcm0> MYHTRW5ITVJ?
AN3-CA M1zrZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnrITWM2OD13LkW2JI5O NITRdpVUSU6JRWK=
HN MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4jXd2lEPTB;NT65OkBvVQ>? M4jQXXNCVkeHUh?=
HCC2218 M4DPUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjoTWM2OD14Lk[xJI5O MXfTRW5ITVJ?
KP-4 NGG4WWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlO5TWM2OD15IH7N MlLkV2FPT0WU
LU-139 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEThV4VKSzVyPUeuO|chdk1? NGLYVlNUSU6JRWK=
ETK-1 M370W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3P3ZWlEPTB;Nz64PEBvVQ>? NVWx[21sW0GQR1XS
Ramos-2G6-4C10 NEPL[|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PXSWlEPTB;OD60PUBvVQ>? NFL1Oo5USU6JRWK=
MHH-PREB-1 NHjmRYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTlwMUKgcm0> MoTYV2FPT0WU
DU-4475 NV\kbII6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\SZolKSzVyPUmuOFQhdk1? MUDTRW5ITVJ?
NCI-H1666 NFG1Zm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnwTWM2OD17LkexJI5O Mne3V2FPT0WU
CAMA-1 NVztSYc{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoH2TWM2OD17Lkigcm0> MoTuV2FPT0WU
TYK-nu MnzES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn:wTWM2OD17Lkm0JI5O MWDTRW5ITVJ?
MFE-280 MnvvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;kTWM2OD17Lkm5JI5O NWT3ephWW0GQR1XS
A549 NWq0W2dqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2fJNGlEPTB;MUCuNVQhdk1? MonMV2FPT0WU
769-P Mn63S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYK0NlZnUUN3ME2xNE41PCCwTR?= MoHTV2FPT0WU
L-363 M4PobWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NED0XZVKSzVyPUGwMlY6KG6P NEWxfYxUSU6JRWK=
ES8 NV3KclZKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\Kb2hKSzVyPUGwMlkhdk1? Mn[1V2FPT0WU
PA-1 NWjHN4VlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDhT|dKSzVyPUGxMlgzKG6P MVHTRW5ITVJ?
Mewo M2LQWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTFzLkm5JI5O NH\nZnVUSU6JRWK=
HSC-3 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWPCfZprUUN3ME2xNk4zOSCwTR?= NUHEd2x2W0GQR1XS
H4 MmTqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NELGc3NKSzVyPUGyMlY4KG6P MmPSV2FPT0WU
BB65-RCC M37aZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrHNWtsUUN3ME2xNk44OiCwTR?= NXzOPXRkW0GQR1XS
NCI-H1793 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\2fJZKSzVyPUGyMlgzKG6P M2To[HNCVkeHUh?=
KARPAS-45 M4Tj[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTF|LkWxJI5O MniwV2FPT0WU
GCT NI\3bnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIr3O5RKSzVyPUGzMlY5KG6P MVvTRW5ITVJ?
EoL-1 NYLEZYVsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\xTWM2OD1zMz65N{BvVQ>? M4TBVHNCVkeHUh?=
LB2241-RCC NGH5e4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTF2LkCxJI5O M{Gwc3NCVkeHUh?=
ES5 NHfLPXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTF2Lke0JI5O MnrNV2FPT0WU
LOXIMVI MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3Eb4RKSzVyPUG0Mlk6KG6P Mo\DV2FPT0WU
COR-L105 M3TKZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzSUlE3UUN3ME2xOU4xPCCwTR?= MYPTRW5ITVJ?
P12-ICHIKAWA M{j0dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTF3LkGgcm0> NGP5[YtUSU6JRWK=
CHL-1 NYPRcnNlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDkNJl[UUN3ME2xOU41PSCwTR?= NH3DcmJUSU6JRWK=
VMRC-RCZ M3S0Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\wTWM2OD1zNT62N{BvVQ>? NH\nPGVUSU6JRWK=
HH M{XKW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\oWXVKSzVyPUG1Mlchdk1? NY\iXYtbW0GQR1XS
NUGC-3 NXvZdnJIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmiyTWM2OD1zNj6zOEBvVQ>? M4LEd3NCVkeHUh?=
EGI-1 NWi3NoRET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWj6SoJqUUN3ME2xOk41OyCwTR?= MXXTRW5ITVJ?
OS-RC-2 NHTWPVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEjFbYVKSzVyPUG2MlQ4KG6P Mn7BV2FPT0WU
MOLT-16 MnfkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\MTWM2OD1zNz6xOUBvVQ>? Mn3RV2FPT0WU
NCI-H209 MnPIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTF5LkK5JI5O M13a[HNCVkeHUh?=
697 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTF5LkSzJI5O MonsV2FPT0WU
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... 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

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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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