BEZ235 (NVP-BEZ235, Dactolisib)

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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BEZ235 (NVP-BEZ235, Dactolisib) 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 M{C5WWFvfGmvaXPyc4Jq[WxiQYPzZZk> Mo\hNVghcA>? NGHVfpVFVVOR MXrBcpRqfHK7cHHuc5NwdWGuIHHjeIl3cXS7IIfpeIghTUN3MDDv[kAxNjByMkWg{txO Moi5NlQ5ODV7NE[=
MCF7 NFTGUHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn[yNE4xOS1zMECg{txO MlG2OFghcA>? Mo\CSG1UVw>? NG\iZ5FKSzVyPUCuO|Mh|ryP NYntWHN5OjN6N{G5NFQ>
HCT116 NX;SOY9OT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PWSVAvODFvMUCwJO69VQ>? M4nMblQ5KGh? NXrZWGUxTE2VTx?= M{nWcGlEPTB;MT6xOkDPxE1? M{mwWVI{QDdzOUC0
U87MG NXnKb2cyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVfZWYNIOC5yMT2xNFAh|ryP NHfhbo41QCCq MkDRSG1UVw>? MYPJR|UxRTFwM{Kg{txO Mk[3NlM5PzF7MES=
HBC4 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVfjbGo{OC5yMT2xNFAh|ryP NVnJOYZlPDhiaB?= NX\WNVkyVG:pIFfJOVA:NThwNkGgUS=> NV;wPZNIOjJ|M{[yOFY>
BSY1 NXvC[IF4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTTNE4xOS1zMECg{txO MWO0PEBp MWDMc4chT0l3ME2tPE41QCCP NXPnXYZpOjJ|M{[yOFY>
HBC5 NFTid3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVKwMlAyNTFyMDFOwG0> M1rvU|Q5KGh? NGnWXGxNd2diR1m1NF0uPy56NzDN MojkNlI{OzZ{NE[=
MCF7 NETw[HdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYKwMlAyNTFyMDFOwG0> M{joVFQ5KGh? NIq5PXRNd2diR1m1NF0uQC5zNjDN MX6yNlM{PjJ2Nh?=
MDA-MB-231 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfHNE4xOS1zMECg{txO MXu0PEBp MnTyUI9oKEeLNUC9MVgvODliTR?= M4rXT|IzOzN4MkS2
U251 MmjTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYmwMlAyNTFyMDFOwG0> MmjKOFghcA>? MV3Mc4chT0l3ME2tO{43PiCP Mor5NlI{OzZ{NE[=
SF268 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFnSXZQxNjBzLUGwNEDPxE1? M{e3XVQ5KGh? MYjMc4chT0l3ME2tO{46OiCP MVWyNlM{PjJ2Nh?=
SF295 NUHXZnpMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHG[lExNjBzLUGwNEDPxE1? MnHyOFghcA>? NYK1NXc3VG:pIFfJOVA:NThwM{GgUS=> NGK5VowzOjN|NkK0Oi=>
SF539 M2nzeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYWwMlAyNTFyMDFOwG0> NH;W[401QCCq MmnLUI9oKEeLNUC9MVgvPTliTR?= NHLpSZQzOjN|NkK0Oi=>
SNB75 NGTjc3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXewMlAyNTFyMDFOwG0> MXS0PEBp MYnMc4chT0l3ME2tPE42QCCP MXKyNlM{PjJ2Nh?=
SNB78 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETrUocxNjBzLUGwNEDPxE1? NGfoenY1QCCq NGTZdoVNd2diR1m1NF0uQC54NTDN MV[yNlM{PjJ2Nh?=
HCC2998 MoKyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYCwMlAyNTFyMDFOwG0> M4nud|Q5KGh? NGX4WGdNd2diR1m1NF0uQC5yNTDN MYCyNlM{PjJ2Nh?=
KM12 MonWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlv4NE4xOS1zMECg{txO NXW0eZFvPDhiaB?= MXXMc4chT0l3ME2tO{42PCCP MWeyNlM{PjJ2Nh?=
HT-29 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1q2TVAvODFvMUCwJO69VQ>? M4THflQ5KGh? NYLYZ5kxVG:pIFfJOVA:NTdwN{WgUS=> MkHHNlI{OzZ{NE[=
HCT15 NYHSSGp4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnTENE4xOS1zMECg{txO MVK0PEBp M4LKeWxw\yCJSUWwQU05NjB|IF2= NXLL[Id2OjJ|M{[yOFY>
HCT116 M2DXSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rkc|AvODFvMUCwJO69VQ>? NYfFdI16PDhiaB?= MnPlUI9oKEeLNUC9MVcvPjFiTR?= MWiyNlM{PjJ2Nh?=
NCI-H23 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUSwMlAyNTFyMDFOwG0> NXfidFh{PDhiaB?= M1:x[mxw\yCJSUWwQU04NjZ2IF2= MUGyNlM{PjJ2Nh?=
NCI-H226 NVjmZphOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknaNE4xOS1zMECg{txO NHr2[IE1QCCq NUnqc|BKVG:pIFfJOVA:NThwNESgUS=> NYT4PIV3OjJ|M{[yOFY>
NCI-H522 NULjTHB5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnzVFRSOC5yMT2xNFAh|ryP MYq0PEBp M13Ecmxw\yCJSUWwQU05NjR3IF2= Mnf6NlI{OzZ{NE[=
NCI-H438 NUHNeYRLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIKxTnQxNjBzLUGwNEDPxE1? M17GbVQ5KGh? NYjoXIFWVG:pIFfJOVA:NThwMUGgUS=> NWLwe|N1OjJ|M{[yOFY>
A549 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVLqTVNlOC5yMT2xNFAh|ryP NF\YfGQ1QCCq MWXMc4chT0l3ME2tPE4xPyCP NXfOUng2OjJ|M{[yOFY>
DMS273 M1X3W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3XVnMxOC5yMT2xNFAh|ryP MoLPOFghcA>? NFW2RnBNd2diR1m1NF0uPy56MDDN MYOyNlM{PjJ2Nh?=
DMS114 MnzHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVKydo5lOC5yMT2xNFAh|ryP MkTZOFghcA>? Moq1UI9oKEeLNUC9MVgvOzliTR?= NHvwcogzOjN|NkK0Oi=>
LOXIMVI MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4r4[VAvODFvMUCwJO69VQ>? M1zMRlQ5KGh? MUTMc4chT0l3ME2tPE43PiCP MoD5NlI{OzZ{NE[=
OVCAR3 NV7zT|ZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXwNE4xOS1zMECg{txO NVPs[oVTPDhiaB?= NFfZ[4NNd2diR1m1NF0uQC5zNzDN NEfnbIozOjN|NkK0Oi=>
OVCAR4 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfFdXVEOC5yMT2xNFAh|ryP MlnFOFghcA>? MXrMc4chT0l3ME2tPE42QCCP MV2yNlM{PjJ2Nh?=
OVCAR5 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF31[24xNjBzLUGwNEDPxE1? M3;XUlQ5KGh? M1L5fGxw\yCJSUWwQU04NjV5IF2= M3i0NFIzOzN4MkS2
OVCAR8 NY\oblF5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEDqcJQxNjBzLUGwNEDPxE1? MlHvOFghcA>? NUHYU|FkVG:pIFfJOVA:NTdwOESgUS=> M{G1dFIzOzN4MkS2
SKOV3 M2SxR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY[wMlAyNTFyMDFOwG0> MVy0PEBp MoHWUI9oKEeLNUC9MVgvPDFiTR?= MXWyNlM{PjJ2Nh?=
RXF631L M{fkeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnSTpYxNjBzLUGwNEDPxE1? NYLSdm1qPDhiaB?= MlLYUI9oKEeLNUC9MVgvOjFiTR?= NH\JcWwzOjN|NkK0Oi=>
ACHN Ml;4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rHUVAvODFvMUCwJO69VQ>? NHGweII1QCCq MlfZUI9oKEeLNUC9MVcvQTViTR?= MnL0NlI{OzZ{NE[=
St-4 MljCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofLNE4xOS1zMECg{txO MWS0PEBp MV7Mc4chT0l3ME2tO{41PyCP NEDQUHczOjN|NkK0Oi=>
MKN1 NV\jOY4{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYiwMlAyNTFyMDFOwG0> MYm0PEBp MnqzUI9oKEeLNUC9MVgvPDFiTR?= NUTrdmlsOjJ|M{[yOFY>
MKN7 NVPZOJN5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX:wMlAyNTFyMDFOwG0> M{LNZlQ5KGh? NW[3XXRmVG:pIFfJOVA:NTdwNkigUS=> NIT4UGszOjN|NkK0Oi=>
MKN28 MkjJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3PibVAvODFvMUCwJO69VQ>? NGLqNI81QCCq MVXMc4chT0l3ME2tO{4xPyCP NX3JbWk4OjJ|M{[yOFY>
MKN45 NY\INlBUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYOwMlAyNTFyMDFOwG0> MkKxOFghcA>? MWLMc4chT0l3ME2tPE4{PCCP NGLCRXUzOjN|NkK0Oi=>
MKN74 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnL4NE4xOS1zMECg{txO NWDkRlFIPDhiaB?= M{DxfGxw\yCJSUWwQU04NjR{IF2= MYqyNlM{PjJ2Nh?=
DU145 NHz6TY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVmwMlAyNTFyMDFOwG0> M4XKb|Q5KGh? NFviT3NNd2diR1m1NF0uQC5zNjDN M2K2XFIzOzN4MkS2
PC3 NFW4PJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXGNE4xOS1zMECg{txO M4[zc|Q5KGh? M{TPXGxw\yCJSUWwQU05NjZ4IF2= MVqyNlM{PjJ2Nh?=
Trypanosoma brucei brucei M3Xlb2Z2dmO2aX;uJGF{e2G7 NEjHXXkzODBibl2= Mn7PNVIhcA>? MUfEUXNQ MonRSIVkemWjc3WgbY4heGixc4Doc5Rq\HmuIHnuc5NqfG:uIIDoc5NxcGG2ZTDs[ZZmdA>? M3yyRVI1QDB3OUS2
Trypanosoma brucei brucei NInNbJJHfW6ldHnvckBCe3OjeR?= NUnSZ5BqOThiaB?= MXzEUXNQ NXX6fogzUW6qaXLpeIlwdiCxZjDy[YNmeHSxcj3t[YRq[XSnZDDlcoRw[3m2b4Ppd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjD0doFve2[ncoLpckB2eHSja3W= MX6yOFgxPTl2Nh?=
Trypanosoma brucei brucei M3;vWmZ2dmO2aX;uJGF{e2G7 M1PRZ|IxOCCwTR?= M3;Q[FEzKGh? M3HYOmROW09? NXXhTHdJTW[oZXP0JI9vKHOyaHnu[49ugWynaX6gcIV3\Wx? NYfTZ4R4OjR6MEW5OFY>
Trypanosoma brucei brucei MV;GeY5kfGmxbjDBd5NigQ>? MVKyNFAhdk1? NVfCV49uOTJiaB?= NY\0TXMxTE2VTx?= MUnF[oZm[3Rib36gdIhwe3CqYYTp[Jlt[2ixbHnu[UBt\X[nbB?= NHzmTHQzPDhyNUm0Oi=>
UM-UC-3 NWPZRZlwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;YTXRKSzVyPUOxOUBxVQ>? NUnWZ4ZUW0GQR1XS
SBC-1 MmjOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PzU2lEPTB;N{SyJJBO M{DDPHNCVkeHUh?=
MKN1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTJwODDuUS=> Mk\MV2FPT0WU
NCI-H720 NEn1XGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4[0TGlEPTB;Mz61O{BvVQ>? MXPTRW5ITVJ?
BFTC-909 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfYVIpKSzVyPUOuO|Ehdk1? M4fxXnNCVkeHUh?=
BPH-1 NEH4NoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MknYTWM2OD12Lke2JI5O NF;6[VJUSU6JRWK=
PC-3 NWfZSXJZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHuTWM2OD13LkC5JI5O NIXzNXNUSU6JRWK=
AN3-CA NXfHR2MzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3ZdHdKSzVyPUWuOVYhdk1? NECzcmJUSU6JRWK=
HN MnPpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEfsfHZKSzVyPUWuPVYhdk1? Mn7JV2FPT0WU
HCC2218 MoLrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHvWWZKSzVyPU[uOlEhdk1? NXzzNodFW0GQR1XS
KP-4 M1ToOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVjh[3JEUUN3ME23JI5O NH7iXnZUSU6JRWK=
LU-139 NIW4[ZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfqSYNKSzVyPUeuO|chdk1? MXvTRW5ITVJ?
ETK-1 M2TYdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVqxc2x3UUN3ME23Mlg5KG6P MYPTRW5ITVJ?
Ramos-2G6-4C10 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorZTWM2OD16LkS5JI5O NH;WTWlUSU6JRWK=
MHH-PREB-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTlwMUKgcm0> M3\BZnNCVkeHUh?=
DU-4475 M13yemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV7CNG9KUUN3ME25MlQ1KG6P M1n6VXNCVkeHUh?=
NCI-H1666 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYm1Z4piUUN3ME25MlcyKG6P MV3TRW5ITVJ?
CAMA-1 NIfYWYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjSW|VKSzVyPUmuPEBvVQ>? NWLWc3FCW0GQR1XS
TYK-nu NFKxTFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DCTGlEPTB;OT65OEBvVQ>? MkDrV2FPT0WU
MFE-280 Mo[5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXP5S2JJUUN3ME25Mlk6KG6P M3LsR3NCVkeHUh?=
A549 MoiwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37jNWlEPTB;MUCuNVQhdk1? M4rjVHNCVkeHUh?=
769-P NIXxcFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDYVnVKSzVyPUGwMlQ1KG6P MmDoV2FPT0WU
L-363 MonqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4H3WGlEPTB;MUCuOlkhdk1? NUTYUnRGW0GQR1XS
ES8 M{jhUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzRTWM2OD1zMD65JI5O MUDTRW5ITVJ?
PA-1 M2e2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPQTWM2OD1zMT64NkBvVQ>? MX\TRW5ITVJ?
Mewo NEG5bJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWq3eWVmUUN3ME2xNU46QSCwTR?= MYTTRW5ITVJ?
HSC-3 NUjPelljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3y2XmlEPTB;MUKuNlEhdk1? NWLRV41XW0GQR1XS
H4 Mmr1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfOVnlKSzVyPUGyMlY4KG6P NV20dYlSW0GQR1XS
BB65-RCC MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfxUVdKSzVyPUGyMlczKG6P NYPOVoRwW0GQR1XS
NCI-H1793 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfpbIRkUUN3ME2xNk45OiCwTR?= MkX5V2FPT0WU
KARPAS-45 NYPldWtLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzsbndFUUN3ME2xN{42OSCwTR?= MVnTRW5ITVJ?
GCT NHP4dJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXXBV2I5UUN3ME2xN{43QCCwTR?= M1XSOnNCVkeHUh?=
EoL-1 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTF|LkmzJI5O MmnCV2FPT0WU
LB2241-RCC M3fGcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{K0eGlEPTB;MUSuNFEhdk1? MnzUV2FPT0WU
ES5 NEmxWmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4nEd2lEPTB;MUSuO|Qhdk1? NHjCRXZUSU6JRWK=
LOXIMVI M{TOXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljSTWM2OD1zND65PUBvVQ>? MmG3V2FPT0WU
COR-L105 NH23fIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjUT|hKSzVyPUG1MlA1KG6P NV7E[HN{W0GQR1XS
P12-ICHIKAWA MlzqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGm4bYZKSzVyPUG1MlEhdk1? NGjNNVFUSU6JRWK=
CHL-1 MlT1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTF3LkS1JI5O NUXYUnF2W0GQR1XS
VMRC-RCZ NXLCV4FqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHFTWM2OD1zNT62N{BvVQ>? NUjXUXhMW0GQR1XS
HH NGL5dYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTF3Lkegcm0> MVnTRW5ITVJ?
NUGC-3 MlL6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\pR2FKSzVyPUG2MlM1KG6P MV\TRW5ITVJ?
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NCI-H522 MnzCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkHtTWM2OD1{NEiuN|Ehdk1? MVPTRW5ITVJ?
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HCC1395 MoO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnBTWM2OD14OUiuOUBvVQ>? M4nm[3NCVkeHUh?=
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NCI-H226 NVPPUJhKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXSTWM2OD15MEeuPEBvVQ>? NV7MdWRLW0GQR1XS
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SW1463 NFHqTGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfjXFVKSzVyPUezPU4yQSCwTR?= NGPlbmdUSU6JRWK=
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NCI-H441 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDkXlc2UUN3ME24PVUvOjJibl2= NE\kS3hUSU6JRWK=
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Mo-T NGj2fnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPzTWM2OD17NEeuPFghdk1? MorxV2FPT0WU
JAR MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHizcI9KSzVyPUm1Ok4zPCCwTR?= NFX6dm1USU6JRWK=
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TE-9 MmH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTnTWM2OD1zLkGyPVc{KM7:TR?= MnvzV2FPT0WU
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NCI-H2029 M1PQbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\PcGFPUUN3ME2xMlQyPzlzIN88US=> M2HFfHNCVkeHUh?=
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KARPAS-299 NH;CPHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXvJR|UxRTFwN{m0O|kh|ryP NIrhSWFUSU6JRWK=
NCI-H358 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWGxcVFPUUN3ME2xMlk2PTB|IN88US=> Ml\WV2FPT0WU
OAW-28 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETHR|lKSzVyPUKuNFY6OTlizszN MoTLV2FPT0WU
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SW1116 MlTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrXTWM2OD1|LkC1OFEyKM7:TR?= M2ThbHNCVkeHUh?=
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SW948 M3O5eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPBTWM2OD12Lke0O|c6KM7:TR?= MlTqV2FPT0WU
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LU-135 Ml;PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXLJR|UxRTZwNEOwO|ch|ryP MYfTRW5ITVJ?
T84 M{\pUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLXTWM2OD14Lkm4OlQh|ryP Mn25V2FPT0WU
CAPAN-1 MlPhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37SbGlEPTB;Nz62NlI{OyEQvF2= M3nhUnNCVkeHUh?=
SW1417 NGjrV4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;xUoVKSzVyPUeuPVE4OzFizszN MkL6V2FPT0WU
BALL-1 M3zTOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3HNTWlEPTB;OD61NFQxQSEQvF2= NELuU2NUSU6JRWK=
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NCI-H1993 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DPRWlEPTB;MUCuOVA5OSEQvF2= M1LKZ3NCVkeHUh?=
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CCRF-CEM M2PFUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYjJR|UxRTF2Lke4NFkh|ryP NHuzT4ZUSU6JRWK=
ZR-75-30 Mm\IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;RfHlFUUN3ME2xOk4{OzB|IN88US=> MYTTRW5ITVJ?
A673 NYqyWZVPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGr6bopKSzVyPUKwMlU2ODdizszN M1TQfHNCVkeHUh?=
K-562 M3fRdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH72RnRKSzVyPUK4MlQyQDNizszN MX\TRW5ITVJ?

... 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 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 (78)

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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