Dactolisib (BEZ235, NVP-BEZ235)

BEZ235 (NVP-BEZ235,Dactolisib)は一種の二重ATP競争性PI3KとmTOR阻害剤で、無細胞試験でp110α/γ/δ/β/mTOR(p70S6K)を抑制する時のIC50値は 4 nM /5 nM /7 nM /75 nM /6 nMそれぞれ分かれます。BEZ235 (NVP-BEZ235,Dactolisib)はT3TopBP1-ER 細胞の中でATRを抑制して、IC50 値が21 nMになって、Akt とPDK1に作用することが弱くなります。臨床2期。

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

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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)は一種の二重ATP競争性PI3KとmTOR阻害剤で、無細胞試験でp110α/γ/δ/β/mTOR(p70S6K)を抑制する時のIC50値は 4 nM /5 nM /7 nM /75 nM /6 nMそれぞれ分かれます。BEZ235 (NVP-BEZ235,Dactolisib)はT3TopBP1-ER 細胞の中でATRを抑制して、IC50 値が21 nMになって、Akt とPDK1に作用することが弱くなります。臨床2期。
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 NV;k[HozSW62aX3pZ5Jw[mmjbDDBd5NigQ>? MmrqNVghcA>? NWTRVo42TE2VTx?= M2DXSWFvfGm2conwZY5we2:vYXygZYN1cX[rdImge4l1cCCHQ{WwJI9nKDBwMECyOUDPxE1? NWPpfJhDOjR6MEW5OFY>
MCF7 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4ruRVAvODFvMUCwJO69VQ>? MXe0PEBp Mm\tSG1UVw>? M{nuSmlEPTB;MD63N{DPxE1? NVPtPY9GOjN6N{G5NFQ>
HCT116 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPlNE4xOS1zMECg{txO NWm3dY56PDhiaB?= MljsSG1UVw>? MoryTWM2OD1zLkG2JO69VQ>? NXLXOoFJOjN6N{G5NFQ>
U87MG NIn5e3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvOTYt5OC5yMT2xNFAh|ryP M3LLNVQ5KGh? NYWzW45PTE2VTx?= NXLa[HR3UUN3ME2xMlMzKM7:TR?= NYHtRVc3OjN6N{G5NFQ>
HBC4 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYS1PJNKOC5yMT2xNFAh|ryP Ml7lOFghcA>? NUDNVlRmVG:pIFfJOVA:NThwNkGgUS=> M1S2TVIzOzN4MkS2
BSY1 M3PET2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX[wMlAyNTFyMDFOwG0> Mn3oOFghcA>? NFPoOXlNd2diR1m1NF0uQC52ODDN NWfjPZdbOjJ|M{[yOFY>
HBC5 NX7CZYpGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mki3NE4xOS1zMECg{txO NXO3bnY1PDhiaB?= MmXjUI9oKEeLNUC9MVcvQDdiTR?= NELPU5MzOjN|NkK0Oi=>
MCF7 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFi4ZZIxNjBzLUGwNEDPxE1? MojTOFghcA>? MoHyUI9oKEeLNUC9MVgvOTZiTR?= NXP6V|NiOjJ|M{[yOFY>
MDA-MB-231 NXzD[nBrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1W2V|AvODFvMUCwJO69VQ>? MUC0PEBp Mn[4UI9oKEeLNUC9MVgvODliTR?= Mkj6NlI{OzZ{NE[=
U251 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfmOlVyOC5yMT2xNFAh|ryP NWj0foJLPDhiaB?= M1rQcWxw\yCJSUWwQU04NjZ4IF2= NHnDTXczOjN|NkK0Oi=>
SF268 MmP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHuxN|QxNjBzLUGwNEDPxE1? NVvZVm9RPDhiaB?= NW\SZ4NrVG:pIFfJOVA:NTdwOUKgUS=> MXGyNlM{PjJ2Nh?=
SF295 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXZNE4xOS1zMECg{txO MmntOFghcA>? MVjMc4chT0l3ME2tPE4{OSCP MU[yNlM{PjJ2Nh?=
SF539 M3uycWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTTSIVJOC5yMT2xNFAh|ryP NW[0bGVjPDhiaB?= NIHaVWxNd2diR1m1NF0uQC53OTDN M4q2bFIzOzN4MkS2
SNB75 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXWwMlAyNTFyMDFOwG0> M2TmTVQ5KGh? MoTBUI9oKEeLNUC9MVgvPThiTR?= NWPIdFd5OjJ|M{[yOFY>
SNB78 NVnmXIt2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX:wMlAyNTFyMDFOwG0> MorSOFghcA>? MoLFUI9oKEeLNUC9MVgvPjViTR?= MX6yNlM{PjJ2Nh?=
HCC2998 NFvvRoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlflNE4xOS1zMECg{txO M33UNFQ5KGh? NH\ZWHNNd2diR1m1NF0uQC5yNTDN M1WwNFIzOzN4MkS2
KM12 MkPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWqwMlAyNTFyMDFOwG0> MXK0PEBp M1PDV2xw\yCJSUWwQU04NjV2IF2= M4rNSlIzOzN4MkS2
HT-29 NV3reI9{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXwdlY6OC5yMT2xNFAh|ryP MnyxOFghcA>? NIjKRodNd2diR1m1NF0uPy55NTDN MlPQNlI{OzZ{NE[=
HCT15 Mke5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjsZYtCOC5yMT2xNFAh|ryP MlzNOFghcA>? NH\LfWJNd2diR1m1NF0uQC5yMzDN NUjQdYg6OjJ|M{[yOFY>
HCT116 MlWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV:wMlAyNTFyMDFOwG0> MWe0PEBp NFH0WHpNd2diR1m1NF0uPy54MTDN NXzRU|RIOjJ|M{[yOFY>
NCI-H23 NXqxUFZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoT5NE4xOS1zMECg{txO NVOyVll7PDhiaB?= NVOy[VFLVG:pIFfJOVA:NTdwNkSgUS=> NHvn[oozOjN|NkK0Oi=>
NCI-H226 Ml;lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\4R|MxNjBzLUGwNEDPxE1? M4nX[|Q5KGh? MUXMc4chT0l3ME2tPE41PCCP MX6yNlM{PjJ2Nh?=
NCI-H522 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUKwMlAyNTFyMDFOwG0> MkKyOFghcA>? MWTMc4chT0l3ME2tPE41PSCP Mme0NlI{OzZ{NE[=
NCI-H438 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEXXTJExNjBzLUGwNEDPxE1? MmXJOFghcA>? MnHGUI9oKEeLNUC9MVgvOTFiTR?= NG\PR2ozOjN|NkK0Oi=>
A549 Mo[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NETN[lQxNjBzLUGwNEDPxE1? MlH4OFghcA>? NV\DVpR5VG:pIFfJOVA:NThwMEegUS=> MnTzNlI{OzZ{NE[=
DMS273 NGTtb5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rOcVAvODFvMUCwJO69VQ>? NYDHU3hDPDhiaB?= MknIUI9oKEeLNUC9MVcvQDBiTR?= NHrwb5QzOjN|NkK0Oi=>
DMS114 M3nL[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX:wMlAyNTFyMDFOwG0> MXm0PEBp MkHrUI9oKEeLNUC9MVgvOzliTR?= MoLJNlI{OzZ{NE[=
LOXIMVI MmnBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX6wMlAyNTFyMDFOwG0> M3LENlQ5KGh? NYrxUnVrVG:pIFfJOVA:NThwNk[gUS=> MnHjNlI{OzZ{NE[=
OVCAR3 Mn\PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4[xV|AvODFvMUCwJO69VQ>? MXO0PEBp MXXMc4chT0l3ME2tPE4yPyCP NUPTXoJZOjJ|M{[yOFY>
OVCAR4 NWPGfGhjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWL0dmUzOC5yMT2xNFAh|ryP M3i3UVQ5KGh? MYTMc4chT0l3ME2tPE42QCCP M2TBN|IzOzN4MkS2
OVCAR5 MmS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVuwMlAyNTFyMDFOwG0> MWW0PEBp MXnMc4chT0l3ME2tO{42PyCP M{XTb|IzOzN4MkS2
OVCAR8 M3q2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4fy[lAvODFvMUCwJO69VQ>? M2LOPVQ5KGh? NFnYPIhNd2diR1m1NF0uPy56NDDN MUCyNlM{PjJ2Nh?=
SKOV3 NWrJUnFLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4DDWFAvODFvMUCwJO69VQ>? M3HTOlQ5KGh? M1LGdWxw\yCJSUWwQU05NjRzIF2= NFzzVlkzOjN|NkK0Oi=>
RXF631L NXH0[lNET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLkXoZSOC5yMT2xNFAh|ryP MlPuOFghcA>? NE\HOodNd2diR1m1NF0uQC5{MTDN NYrXcJV5OjJ|M{[yOFY>
ACHN NFvQUmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTRNE4xOS1zMECg{txO NULobZNSPDhiaB?= NW[2N2dJVG:pIFfJOVA:NTdwOUWgUS=> M{T2U|IzOzN4MkS2
St-4 M{THXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LId|AvODFvMUCwJO69VQ>? M4naWlQ5KGh? NWmzeHFSVG:pIFfJOVA:NTdwNEegUS=> MW[yNlM{PjJ2Nh?=
MKN1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M360U|AvODFvMUCwJO69VQ>? MW[0PEBp MVvMc4chT0l3ME2tPE41OSCP M2D4VlIzOzN4MkS2
MKN7 NFjwVodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4n4WVAvODFvMUCwJO69VQ>? M4TmV|Q5KGh? MWTMc4chT0l3ME2tO{43QCCP NIPoWYUzOjN|NkK0Oi=>
MKN28 MmfWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVGwMlAyNTFyMDFOwG0> NVu1eZRvPDhiaB?= NIrQ[JFNd2diR1m1NF0uPy5yNzDN M4nn[FIzOzN4MkS2
MKN45 MlvSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1my[lAvODFvMUCwJO69VQ>? MYq0PEBp NGDIPGtNd2diR1m1NF0uQC5|NDDN MXeyNlM{PjJ2Nh?=
MKN74 NYLaT3hIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYiwMlAyNTFyMDFOwG0> MXm0PEBp NYi4TWpRVG:pIFfJOVA:NTdwNEKgUS=> MkWwNlI{OzZ{NE[=
DU145 NUfnWWRkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjNS3Y4OC5yMT2xNFAh|ryP MUS0PEBp NVj3T|hFVG:pIFfJOVA:NThwMU[gUS=> NGixXlIzOjN|NkK0Oi=>
PC3 M2DUUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4DoT|AvODFvMUCwJO69VQ>? NU\OT3BQPDhiaB?= NYK0eHl4VG:pIFfJOVA:NThwNk[gUS=> M3HROVIzOzN4MkS2
Trypanosoma brucei brucei MoLwSpVv[3Srb36gRZN{[Xl? MYOyNFAhdk1? NIPKPXgyOiCq M4\IPWROW09? MlvsSIVkemWjc3WgbY4heGixc4Doc5Rq\HmuIHnuc5NqfG:uIIDoc5NxcGG2ZTDs[ZZmdA>? NGHyOoMzPDhyNUm0Oi=>
Trypanosoma brucei brucei NITY[XNHfW6ldHnvckBCe3OjeR?= M1rYRVE5KGh? NFm4d21FVVOR MmHPTY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? M2e4TlI1QDB3OUS2
Trypanosoma brucei brucei NGnab2ZHfW6ldHnvckBCe3OjeR?= MYeyNFAhdk1? M{PFWlEzKGh? MX7EUXNQ MYDF[oZm[3Rib36gd5BpcW6pb335cIVqdiCuZY\lcC=> MVOyOFgxPTl2Nh?=
Trypanosoma brucei brucei M2P6WWZ2dmO2aX;uJGF{e2G7 NXfWWJBWOjByIH7N MknONVIhcA>? M4\sfWROW09? NWi4b5RFTW[oZXP0JI9vKHCqb4PwbIF1cWS7bHPoc4xqdmVibHX2[Yw> MXOyOFgxPTl2Nh?=
UM-UC-3 NEjzUZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvUTWM2OD1|MUWgdG0> MXzTRW5ITVJ?
SBC-1 NIX0e|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1Hh[mlEPTB;N{SyJJBO NWfvTnFvW0GQR1XS
MKN1 MmjnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jhWGlEPTB;Mj64JI5O NYjTOZlmW0GQR1XS
NCI-H720 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHQWZlKSzVyPUOuOVchdk1? MnXwV2FPT0WU
BFTC-909 NXnwRpNiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfKU4NKSzVyPUOuO|Ehdk1? NELPV|VUSU6JRWK=
BPH-1 NFL1d5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHvTWM2OD12Lke2JI5O Mnn1V2FPT0WU
PC-3 NWjDemhKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXHJR|UxRTVwMEmgcm0> MnzMV2FPT0WU
AN3-CA M2fRPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXJbVZWUUN3ME21MlU3KG6P NUP5d281W0GQR1XS
HN NU\lUWtET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlG1TWM2OD13Lkm2JI5O MorrV2FPT0WU
HCC2218 NFHDOW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\mTWM2OD14Lk[xJI5O MXXTRW5ITVJ?
KP-4 NVXuVpZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPiTFVKSzVyPUegcm0> M1H6dnNCVkeHUh?=
LU-139 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLIdGZbUUN3ME23Mlc4KG6P Ml;uV2FPT0WU
ETK-1 M1H5bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnnVmZKSzVyPUeuPFghdk1? MWnTRW5ITVJ?
Ramos-2G6-4C10 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjiV3lWUUN3ME24MlQ6KG6P MmGyV2FPT0WU
MHH-PREB-1 Mn3hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfEOYxtUUN3ME25MlEzKG6P M16z[3NCVkeHUh?=
DU-4475 NEix[pFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTJTWM2OD17LkS0JI5O M3iz[3NCVkeHUh?=
NCI-H1666 M3vtfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUHwd2Z7UUN3ME25MlcyKG6P NF;Wc|JUSU6JRWK=
CAMA-1 M3;KWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\4eWlEPTB;OT64JI5O MWrTRW5ITVJ?
TYK-nu M1KzSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWG4Vnh[UUN3ME25Mlk1KG6P MVnTRW5ITVJ?
MFE-280 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFj4NJVKSzVyPUmuPVkhdk1? NUT6c2pnW0GQR1XS
A549 NH7zbnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PITGlEPTB;MUCuNVQhdk1? MnLpV2FPT0WU
769-P MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjhV2lKSzVyPUGwMlQ1KG6P NXnBXlV6W0GQR1XS
L-363 MlfVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVrJR|UxRTFyLk[5JI5O MoPlV2FPT0WU
ES8 NEWwOVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIP2NpJKSzVyPUGwMlkhdk1? NEnySXBUSU6JRWK=
PA-1 NIew[GZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHj6N|lKSzVyPUGxMlgzKG6P MVvTRW5ITVJ?
Mewo MnPSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYXIbJJ6UUN3ME2xNU46QSCwTR?= MXTTRW5ITVJ?
HSC-3 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV7UdW5jUUN3ME2xNk4zOSCwTR?= MoXyV2FPT0WU
H4 M2H6Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDoWJRKSzVyPUGyMlY4KG6P NUTpWnJ[W0GQR1XS
BB65-RCC MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;RO2lEPTB;MUKuO|Ihdk1? M{iyZ3NCVkeHUh?=
NCI-H1793 M3PUZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHQcoo{UUN3ME2xNk45OiCwTR?= NHPt[lhUSU6JRWK=
KARPAS-45 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3jiTGlEPTB;MUOuOVEhdk1? Mme4V2FPT0WU
GCT M3jpSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvDWJk1UUN3ME2xN{43QCCwTR?= NFruUYRUSU6JRWK=
EoL-1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2n5emlEPTB;MUOuPVMhdk1? MUHTRW5ITVJ?
LB2241-RCC NV;ZcmZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnjSIJkUUN3ME2xOE4xOSCwTR?= NX6xO3lzW0GQR1XS
ES5 MoK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTF2Lke0JI5O MXrTRW5ITVJ?
LOXIMVI MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HDdWlEPTB;MUSuPVkhdk1? NID4WmhUSU6JRWK=
COR-L105 M122[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2fsbGlEPTB;MUWuNFQhdk1? M1jvPXNCVkeHUh?=
P12-ICHIKAWA MlvrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1X2SWlEPTB;MUWuNUBvVQ>? M{fPZXNCVkeHUh?=
CHL-1 Mn72S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nZPWlEPTB;MUWuOFUhdk1? NHf4eItUSU6JRWK=
VMRC-RCZ M2X5WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFTTNHVKSzVyPUG1MlY{KG6P MWHTRW5ITVJ?
HH MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vaXWlEPTB;MUWuO{BvVQ>? NHHHOoJUSU6JRWK=
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CCRF-CEM MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moq0TWM2OD1zND63PFA6KM7:TR?= MWrTRW5ITVJ?
ZR-75-30 M2mwRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTNRmFKSzVyPUG2MlM{ODNizszN MULTRW5ITVJ?
A673 MnvyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzmRYNKSzVyPUKwMlU2ODdizszN NFPUW|ZUSU6JRWK=
K-562 MkPYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTJ6LkSxPFMh|ryP MXvTRW5ITVJ?

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

C30H23N5O

CAS No. 915019-65-7
保管 3年-20℃
2年-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)
Water <1 mg/mL
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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