MK-2206 2HCl 化学構造
分子量: 480.39

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製品説明

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製品の説明

生物活性

製品説明 MK-2206 2HClは高度選択的に Akt1, Akt2 and Akt3を抑制して、 IC50がそれぞれ 8 nM, 12 nM と 65 nMになる。
ターゲット Akt1 Akt2 Akt3
IC50 8 nM 12 nM 65 nM [1]
In vitro試験 MK-2206 is an allosteric inhibitor and is activated by the pleckstrin homology domain. MK-2206 inhibits auto-phosphorylation of both Akt T308 and S473. MK-2206 also prevents Akt-mediated phosphorylation of downstream signaling molecules, including TSC2, PRAS40 and ribosomal S6 proteins. [1] MK-2206 inhibits Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292) more potently when compared to Ras-mutant cell lines (NCI-H358, NCI-H23, NCI-H1299, and Calu-6). MK-2206 also shows synergistic responses in combination with cytotoxic agents such as erlotinib or lapatinib in lung NCI-H460 or ovarian A2780 tumor cells. [2] MK-2206 or siRNA-mediated Akt inhibition strongly activates autophagy in human glioma cells. However, eukaryotic elongation factor-2 (eEF-2) silencing suppresses MK-2206-induced-autophagy, with a promotion of apoptotic cell death. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity Description
NCI-H292 M3LOUGN6fG:2b4jpZ{BCe3OjeR?= NETyNnA{KM7:TR?= NWfxWWFNPzJiaB?= MV;EUXNQ M3jzRmlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:w
A431 MXTLbY5ie2ViQYPzZZk> NVr3TmlDPSEQvF2= NX3rdWZEPSCq NWLEZXlmTE2VTx?= NVWx[YNOW3WycILld5NmeyC2aHWgd4lodmGuaX7nJI9nKEGtdDDhcoQhTXKt
HepG2 MWnDfZRwfG:6aXOgRZN{[Xl? M{jJZlExKM7:TR?= M1;adlI1KGh? NVjITG9TTE2VTx?= MUjT[Y5{cXSrenXzJJJme2m|dHHueEBk\WyuczD0c{B1cGViY4n0c5RwgGmlIHXm[oVkfCCxZjDzc5Ji\mWwaXK=
Sk-Hep1 MnjDR5l1d3SxeHnjJGF{e2G7 MnLsNVAh|ryP NWOycmFXOjRiaB?= NGXYR5hFVVOR NEfvS21U\W6|aYTpfoV{KHKnc3nzeIFvfCClZXzsd{B1dyC2aHWgZ5l1d3SxeHnjJIVn\mWldDDv[kB{d3KjZnXubYI>
OCUT1 cells harbored PIK3CA (H1047R+/+) NHvReoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\zdFMh|ryP NX\uZ|d[PSCm MV7EUXNQ M4jMXGlEPTB;MD6xOEDPxE1?
K1 cells harbored PIK3CA (E542K+/+) MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3IfWE{KM7:TR?= NIfIWZg2KGR? MXLEUXNQ MX3JR|UxRTBwNUKg{txO
FTC133 cells harbored PTEN (allele deletion and R130+) MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXyzJO69VQ>? MnflOUBl MWLEUXNQ M{HxdGlEPTB;MD6xPEDPxE1?
C643 cells harbored HRAS (G13R+/−) NUT5V5Z1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmHDN{DPxE1? NWj0[G1kPSCm MmTmSG1UVw>? NWnlPY1lUUN3ME2wMlI4KM7:TR?=
Hth7 cells harbored NRAS (Q61R+/−) NW[0O4s1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7CNlE{KM7:TR?= MWW1JIQ> MWjEUXNQ NVXE[nJSUUN3ME20MlUh|ryP
TPC1 cells harbored RET/PTC1 rearrangement M3m0emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY[zJO69VQ>? MYS1JIQ> NF3mSWlFVVOR NU\ieIt{UUN3ME2wMlU6KM7:TR?=
Hth74 M{nEbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFe4Opg{KM7:TR?= MYC1JIQ> MXzEUXNQ NIXjPJhKSzVyPUKuNVkh|ryP
KAT18 MnzSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3q0[|Mh|ryP NVjae2NSPSCm M3\HWmROW09? NHvQN2VKSzVyPUSuOlIh|ryP
SW1736 NU\IbIlbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnn4NVAxKM7:TR?= MmDrOUBl MV7EUXNQ M3\uPWlEPTB;NEeuOVYh|ryP
WRO NWH2TGp{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjVc4kyODByIN88US=> MWO1JIQ> Mn3FSG1UVw>? NWPLdIUyUUN3ME6xNFAxKM7:TR?=
TAD2 MmHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPPR|YyODByIN88US=> MV21JIQ> NHXqNY5FVVOR M3nFR2lEPTB-MUCwNEDPxE1?
LN229 NIfVVGVCeG:ydH;zbZMhSXO|YYm= MXmwMlUh|ryP NIH0Wnk3OCCq M2XXUmROW09? MkjLRZVodWWwdIOgZZBweHSxZ3XubYMh\W[oZXP0d{Bw\iCpZX\peIlvcWJ?
T98G NUH2eFdvSXCxcITvd4l{KEG|c3H5 NWnTRZNEOC53IN88US=> NHPqSZE3OCCq NVLGNJFDTE2VTx?= MUHBeYdu\W62czDhdI9xfG:pZX7pZ{Bm\m[nY4TzJI9nKGenZnn0bY5q[g>?
HC11 MV7GeY5kfGmxbjDBd5NigQ>? NIT0VI8yOCEQvF2= Mo\RNlQhcA>? MUHEUXNQ M2i5W2lvcGmkaYTzJO6zNWOjc3XpckBidmRiQVTSVEB{gW62aHXzbZM>
MOLT-4 Ml;5R5l1d3SxeHnjJGF{e2G7 MoHTNVAh|ryP NWr0NXRWPDhiaB?= M37scmROW09? M{DCT2lEPTB;MT635qCK|ryP
CEM-R MlTsR5l1d3SxeHnjJGF{e2G7 MWOxNEDPxE1? MUW0PEBp MoTVSG1UVw>? NFjlfZZKSzVyPUOuN-KBkc7:TR?=
CEM-S NXGzN2VYS3m2b4TvfIlkKEG|c3H5 M17FfVExKM7:TR?= MX[0PEBp MmDVSG1UVw>? MX;JR|UxRTVwMfMAje69VQ>?
MOLT-4 M3HwdGZ2dmO2aX;uJGF{e2G7 MlXsNVAh|ryP MmDPNlQhcA>? Mni2SG1UVw>? NWi3NJVlSmyxY3vzJINmdGy|IHnuJJRp\SCJMD;HNUBxcGG|ZTDv[kB1cGViY3XscEBkgWOuZR?=
MOLT-4 NFr1fXBHfW6ldHnvckBCe3OjeR?= NFzxPJo16oDLzszN NHK2TFA1KGh? NVrCcphPTE2VTx?= M2naSWlv[3KnYYPld{B1cGViYX3veY51KG:oIHPs[YF3\WRiTFOzRU9DNCCjIIflcIwu\XO2YXLsbZNp\WRiYYX0c5Bp[We7IH3hdotmeg>?
CEM-R NFT5ZnpHfW6ldHnvckBCe3OjeR?= NIjrPG016oDLzszN NYju[Iw5PCCq MYjEUXNQ MmTiTY5kemWjc3XzJJRp\SCjbX;1cpQhd2ZiY3zlZZZm\CCOQ{TBM2ItKGFid3XscE1me3SjYnzpd4hm\CCjdYTvdIhi\3libXHyb4Vz
CEM-S NIPmcIlHfW6ldHnvckBCe3OjeR?= Mn7iOQKBkc7:TR?= MkjMOEBp NEfaUo9FVVOR NYO1d5VRUW6lcnXhd4V{KHSqZTDhcY92dnRib3[gZ4xm[X[nZDDMR|VCN0JuIHGge4VtdC2nc4ThZoxqe2inZDDheZRweGijZ4mgcYFzc2W{
HepG2 cell Mmj3T4lv[XOnIFHzd4F6 M{j2XVIxKM7:TR?= M1rUe|I1KGh? MnPnSG1UVw>? M3XMemRwf26{ZXf1cIF1\XNidHjlJJBpd3OyaH;yfYxifGmxbjDv[kBCU1R?
HepG2 cell NVXWVFA2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWjPc2tnOzBizszN M1XzZVI1KGh? NFW4dY1FVVOR NFnFdmxKdmirYnn0d{Bk\WyuIHfyc5d1cA>?
HepG2 cell NIHNV5RCeG:ydH;zbZMhSXO|YYm= MV:yNEDPxE1? MVqyOEBp NIfLd5VFVVOR Mn\5TY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?
GEO MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXq1NFAhdk1? MnXGO|IhcA>? MVLEUXNQ MoDMTY5pcWKrdIOgZ4VtdCCpcn;3eIg>
CNE-1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3j5NVExKM7:TR?= NGe0ZnM6PiCq M1;iXWROW09? M3fP[2lEPTB;Mj65OkDPxE1?
CNE-2 NX:zOG91T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrzPVJOOTBizszN MYi5OkBp NFHFPY1FVVOR MnfkTWM2OD12LkWzJO69VQ>?
HONE-1 M33ROWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13CeFExKM7:TR?= M2GzWVk3KGh? NXrQdYxxTE2VTx?= NUPiTWxPUUN3ME2zMlM4KM7:TR?=
SUNE-1 M3G3ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzMSZlpOTBizszN NIfOeFY6PiCq MVnEUXNQ MYLJR|UxRTBwNUKg{txO
CNE-2 NHu3WYxHfW6ldHnvckBCe3OjeR?= MorRNVAh|ryP MnK4OFghcA>? MUDEUXNQ MUXJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHH0JGcy
HONE-1 MlLFSpVv[3Srb36gRZN{[Xl? NHXnW2gyOCEQvF2= NF3McIQ1QCCq MWTEUXNQ MXfJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHH0JGcy
NEC8 NV;kU5FPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zz[WlEPTB;MD6wPVY2OSEQvF2=
P12-ICHIKAWA MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFXkdFBKSzVyPUCuNVE3OiEQvF2=
MDA-MB-175-VII MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1POSmlEPTB;MD6xN|c{QCEQvF2=
AsPC-1 Mkm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLGN5V1UUN3ME2wMlIzOTJ{IN88US=>
T47D NEXhTVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmGzTWM2OD1yLkK4NlUh|ryP
HH M2T1PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\sUmlEPTB;MD6zNFI5OyEQvF2=
MOLT-16 NHKycXZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\XXJVKSzVyPUCuN|A{OiEQvF2=
ES5 Ml;BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3:2cmlEPTB;MD6zOFQ2PSEQvF2=
RS4-11 MknyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnn4TWM2OD1yLkO0OlEh|ryP
KARPAS-45 NU[2bWlOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHHPZ2NKSzVyPUCuN|c{OjFizszN
NCI-H720 M2XsU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TKSGlEPTB;MD6zO|Y4QSEQvF2=
H9 MmT1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1:4Z2lEPTB;MD6zPFg5OyEQvF2=
EFM-19 M2nvN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnOcWRKSzVyPUCuOFQxOSEQvF2=
SBC-1 NX20dnEyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTBwNESwN|Uh|ryP
A4-Fuk M2nibWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XE[WlEPTB;MD60Olg3QCEQvF2=
NCI-H1563 M1nDemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2f5PWlEPTB;MD60PFE5QSEQvF2=
HCC1419 NGrhflZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvCTWM2OD1yLkS4PFkzKM7:TR?=
H-EMC-SS NHG2[mNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPlOG0zUUN3ME2wMlQ6QTN7IN88US=>
BHT-101 NXv2R4M2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TEbWlEPTB;MD61Nlk3OSEQvF2=
IGROV-1 M176Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7JPIZNUUN3ME2wMlU2OjR7IN88US=>
HGC-27 MlzwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXhT5pKSzVyPUCuOVY4QDNizszN
MDA-MB-361 NE\IPYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHSxbYxKSzVyPUCuOVc4PjFizszN
KE-37 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTmPWp{UUN3ME2wMlU5OjZizszN
HCC70 MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3LyS2lEPTB;MD61PVgzPyEQvF2=
LNCaP-Clone-FGC NW\abYhjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnW1TWM2OD1yLk[xNFQ5KM7:TR?=
HAL-01 NEj4OWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\Rb2pVUUN3ME2wMlYzOTNizszN
HT NWnJXnJKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13i[WlEPTB;MD62N|I{QSEQvF2=
MDA-MB-415 NEf3TZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzDSGlKSzVyPUCuOlM3OjZizszN
NOS-1 Ml7IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PoPWlEPTB;MD62N|czOyEQvF2=
DU-145 Mlj3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{XBdGlEPTB;MD62OFc1PSEQvF2=
OCUB-M NIDnUJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrl[5FOUUN3ME2wMlcxQTZ4IN88US=>
VA-ES-BJ NVXyT5VXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnr1TWM2OD1yLkezNFI2KM7:TR?=
J-RT3-T3-5 NHHPfVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;jdlVuUUN3ME2wMlc1PDB|IN88US=>
MOLT-4 Mo\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXUN3NKSzVyPUCuPFA2QDJizszN
NB7 NH63NlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFH2WmhKSzVyPUCuPFI1OTFizszN
L-363 M3vDSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVezRY1tUUN3ME2wMlg{PDR{IN88US=>
NKM-1 NHq2TXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\3VGlEPTB;MD64OlI2OyEQvF2=
HOP-92 M4PkPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mm\3TWM2OD1yLki3NlI{KM7:TR?=
OAW-42 M{TLV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvjd2VKSzVyPUCuPFg4OiEQvF2=
HuO9 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTu[4ppUUN3ME2wMlkzPzVzIN88US=>
MFE-280 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHLEN5BKSzVyPUCuPVY1PjVizszN
EM-2 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELXVnVKSzVyPUCuPVc6OzlizszN
NCI-H520 NHfCcGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXzJR|UxRTBwOUi1PVIh|ryP
LB2241-RCC MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml[yTWM2OD1yLkm5O|M1KM7:TR?=
SK-NEP-1 NXjmfFBYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUW5c4VPUUN3ME2xMlE1PDh3IN88US=>
LXF-289 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIS4NItKSzVyPUGuNVcyPTZizszN
EPLC-272H M1\veWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLtTmhKSzVyPUGuNVczPTZizszN
COLO-684 MoKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLaTWM2OD1zLkKzO|I2KM7:TR?=
ES1 M1Lhfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkHkTWM2OD1zLkK0NFY2KM7:TR?=
DOHH-2 NIrvZ|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTFwMkiyNFMh|ryP
CTB-1 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTFwMki5PUDPxE1?
G-401 M{KzcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojITWM2OD1zLkK5O|k2KM7:TR?=
LoVo MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHHTWM2OD1zLkOyOVM1KM7:TR?=
Ramos-2G6-4C10 MlTsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\l[WlEPTB;MT6zN|cxOSEQvF2=
MFM-223 NGi3U45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\oTWM2OD1zLkO0OFYyKM7:TR?=
PA-1 NFnxelFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXTTWM2OD1zLkO1NlY2KM7:TR?=
697 NXLZUo0zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTFwM{e2NVYh|ryP
QIMR-WIL M13MVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrGW4FuUUN3ME2xMlQ6OTF4IN88US=>
HOS M4jkcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzJe2hCUUN3ME2xMlQ6PTV6IN88US=>
DMS-273 NGG4VG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfxTWM2OD1zLkWxPVU6KM7:TR?=
ME-180 M3PSSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLvPZZVUUN3ME2xMlU3QDlzIN88US=>
HCC2218 NUPzbI1tT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\MXmpQUUN3ME2xMlY5OjJ3IN88US=>
CAL-54 NVrm[2dCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLGbFZrUUN3ME2xMlcyOjR{IN88US=>
OMC-1 NYnkRVM2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;FbolwUUN3ME2xMlc1Pjd5IN88US=>
COR-L105 M3v4T2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\N[GlEPTB;MT63PVc{PyEQvF2=
BV-173 NIXK[IxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTFwOEGwO|Qh|ryP
RKO NFuwXoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\5fWlEPTB;MT64O|ExOSEQvF2=
SNU-387 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTDTWM2OD1zLki4OFA3KM7:TR?=
SW1088 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHhd3VKSzVyPUGuPVQ3ODZizszN
Hs-578-T M1vsZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIf4ZopKSzVyPUKuNVE1OzNizszN
OC-314 MnPyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXP0NJRQUUN3ME2yMlE2ODh4IN88US=>
RMG-I Mor2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jNeWlEPTB;Mj6xOlM6QCEQvF2=
NCI-H1395 NF7Nb4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1fid2lEPTB;Mj6xPFA6OSEQvF2=
GAMG NYjmS2duT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3KPHh5UUN3ME2yMlI{QDR3IN88US=>
LB1047-RCC MonKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;1TWM2OD1{LkK0N|E4KM7:TR?=
MN-60 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;ve2lEPTB;Mj6yPVkzOyEQvF2=
OAW-28 MlrQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fj[2lEPTB;Mj6yPVk2OSEQvF2=
NCI-H2228 NVvlboR[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUm0U2dtUUN3ME2yMlMyPTV{IN88US=>
ABC-1 NGOzPGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkfPTWM2OD1{LkOzNlU{KM7:TR?=
LS-513 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHrLTWNKSzVyPUKuN|M1QDRizszN
KS-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI[4Um5KSzVyPUKuN|gyQTFizszN
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K-562 Ml7RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXNV3VKSzVyPUO4N{4{PiEQvF2=
SBC-5 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfrTWM2OD1|OE[uPVg2KM7:TR?=
NB17 MnP2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4myN2lEPTB;M{myMlU6PiEQvF2=
NCI-H2052 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHTSd5BKSzVyPUO5PE41PzJizszN
HCC38 NVr6XpduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoLLTWM2OD12MEGuOVk{KM7:TR?=
NCI-H69 MkXwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV7nfXRbUUN3ME20OFEvODh|IN88US=>

... Click to View More Cell Line Experimental Data

In vivo試験 MK-2206 shows 60% TGI and inhibits more than 70 % of phospho-Akt1/2 (T308 and S473) in A2780 ovarian cancer xenografts at a dose of 240 mg/kg. [1] MK-2206 exhibits significant antitumor activity in NCI-H292 xenograft in combination with erlotinib or lapatinib. [2]
臨床試験 MK-2206 is currently under Phase II clinical trial for treatment of ovarian cancer, primary peritoneal cancer and fallopian tube cancer.
特集 The first allosteric small molecule inhibitor of Akt to enter clinical development.

プロトコル (参考用のみ)

キナーゼアッセイ: [4]

Akt kinases assay Akt kinases are assayed by a GSK-derived biotinylated peptide substrate. The extent of peptide phosphorylation is determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which will bind to the biotin moiety on the peptide. When the Lance and APC are in proximity, a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 655 nm. Working Solution: 100X protease inhibitor cocktail (PIC): 1mg/mL benzamidine, 0.5 mg/mL pepstatin, 0.5 mg/mL leupeptin, 0.5 mg/mL aprotinin; 10X assay buffer: 500 mM HEPES, pH7.5, 1% PEG, 16.6 mM EDTA, 1 mM EGTA, 1% BSA, 20 mM 9-glycerol phosphate; Quench buffer 50 mM HEPES pH 7.3, 16.6 mM EDTA, 0.1% BSA, 0.1% Triton X-100, 0.17 nM labeled monoclonal antibody, 0.0067 mg/mL SA-APC; ATP/MgCl2 working solution: 1X Assay buffer, 1 mM DTT, 1X PIC, 5% glycerol, active Akt; Peptide working solution: 1X Assay buffer, 1 mM DTT, 1X PIC, 5% glycerol, 2 TM GSK biotinylated peptide. The reaction is assembled by adding 16 µL of ATP/MgCl2 working solution to the appropriate wells. MK-2206 or vehicle (1.0 µL) is added followed by 10 µL of peptide working solution. The reaction is started by adding 13 μL of the enzyme working solution and mixing. The reaction is allowed to proceed for 50 min and then stopped by the addition of 60 µL HTRF quench buffer. The stopped reactions are incubated at room temperature for at least 30 min and then read in the instrument.

細胞アッセイ: [2]

細胞株 A431, HCC827, NCI-H292, NCI-H358, NCI-H23, NCI-H1299, Calu-6 and NCI-H460 cells
濃度 0, 0.3, 1 and 3 μM
反応時間 72 or 96 hours
実験の流れ MK-2206 is dissolved in DMSO as a stock solution and diluted by culture media before use. Cells are seeded at a density of 2-3 × 103 in 96-well plates and incubated for 24 hours. Then MK-2206 (0, 0.3, 1 and 3 μM) is added to the cells. Cell proliferation is determined after 72 or 96 hours.

動物実験: [2]

動物モデル SK-OV-3, NCI-H292, HCC70, PC-3, and NCI-H460 models in male CD1-nude mice
製剤 Formulated in 30% Captisol
投薬量 120 mg/kg
投与方法 Orally administered

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 MK-2206 2HCl SDF
分子量 480.39
化学式

C25H21N5O.2HCl

CAS No. 1032350-13-2
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 14 mg/mL (29.14 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 15% Captisol 17 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 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one

カスタマーフィードバック (19)


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Rating
Source Cancer Cell, 2013, 24, 766-76. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines T-ALL cells
Concentrations 10 uM
Incubation Time 5 h
Results western blot analysis with the AKT phosphorylationmotif antibody showed decreased AKT phosphorylated NR3C1in NR3C1 immunoprecipitates from CCRF-CEM T-ALL cellsupon AKT inhibition with MK2206

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Source Cancer Cell, 2013, 24, 766-76. MK-2206 2HCl purchased from Selleck
Method flow cytometry
Cell Lines immunodeficient NOG mice
Concentrations 10 mg kg-1
Incubation Time 3 days
Results AKT1 inhibition of CCRF-CEM lymphoblasts with MK2206 effectivelyrestored glucocorticoid-induced apoptosis and reversed glucocorticoid resistance in vitro.

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Source Cancer Cell, 2013, 24, 766-76. MK-2206 2HCl purchased from Selleck
Method analysis of luciferase activity
Cell Lines immunodeficient NOG mice
Concentrations 10 mg kg-1
Incubation Time 3 days
Results In this experiment, animalstreated with dexamethasone or MK2206 showed progressivetumor growth similar to that observed in vehicle-treated controls,while mice treated with MK2206 plus dexamethasone had significant antitumor responses.

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Source Cancer Discov, 2012, 2, 934-47. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines PC9GR4/WZR10 cells
Concentrations 1 uM
Incubation Time 72 h
Results The addition of a dual PI3K and MTOR inhibitor, PI103, or the AKT inhibitor MK-2206, did reduce the expression of pAKT neither in GR4 cells nor WZR10 cells.

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Source J Exp Med, 2014, 211(9), 1741-58. MK-2206 2HCl purchased from Selleck
Method 3D migration model
Cell Lines WT or Rap1b-/- neutrophil
Concentrations 2 uM
Incubation Time
Results MK-2206 treatment completely reversed elevated TEM across mouse endothelial cells of Rap1b-/- neutrophils to WT levels (A). It reduced ECM degradation of Rap1b -/- neutrophils, and inhibited their multiple protrusions (B and C). Furthermore, almost all Rap1b -/- cells treated with MK-2206 were found at the endothelial cell junctions (D).

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Source Nat Commun, 2015, 6:6943. MK-2206 2HCl purchased from Selleck
Method Western Blot
Cell Lines HUVECs
Concentrations 1 uM
Incubation Time 8 h
Results Because YAP is also a known substrate of Akt21, we examined whether blockade of the Akt pathway affects YAP phosphorylation. Both Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and MK-2206, an allosteric inhibitor of Akt, suppressed cell contact-mediated YAP phosphorylation.

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Source Leukemia, 2015, 29(1), 169-76. MK-2206 2HCl purchased from Selleck
Method Immunoblotting
Cell Lines CXCR4S338X-expressing BCWM.1 cells
Concentrations 0.5 uM
Incubation Time 6 h
Results As AKT and ERK, but not BTK, show continued SDF-1a-triggered activation in CXCR4S338X-expressing WM cells treated with ibrutinib, we next sought to clarify if AKT and ERK contributed to the enhanced survival of these cells. It therefore treated SDF-1acultured CXCR4S338X BCWM.1 cells with either AKT- (MK-2206 and AZD-5363) or MEK- (AS-703026, AZD-6244 and UO126) specific inhibitors with and without ibrutinib (0.5 uM) for 6 h so as to clarify the contribution of AKT and ERK to ibrutinib resistance. The inhibitory activity of MK-2206, as well as AS-703026, AZD-6244 and UO126 was confirmed by western blot analysis for pAKT (S473) and pERK (T202/Y204), respectively.

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Rating
Source Cancer Res, 2013, 73, 2189-98. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines SKNAS/SJNB8/IMR32/GIMEN/SHEP2/KCNR/NGP/LAN1/LAN5/TR14/UHGNP cell lines
Concentrations 8 μM
Incubation Time 48 h
Results The 8 μM MK-2206 treatments resulted in effective pathway inhibition in all cell lines as shown by western blot for phosphoryl ated FOXO3a and PRAS40 as well as AKT serine 473 phosphorylation.

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Rating
Source Oncotarget, 2011, 2, 1109-26. MK-2206 2HCl purchased from Selleck
Method Western blot/ Wst-1 assay
Cell Lines ATC/ FTC cell lines
Concentrations 500 nM
Incubation Time 1 h/72 h
Results One-hour treatment with the AKT inhibitor MK-2206 (0.5 μM) or with the MEK inhibitor U0126 (10 μM) effectively abolished AKT and ERK1/2 phosphorylation in all cell lines.

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Rating
Source Sci Signal, 2011, 4, rs9. MK-2206 2HCl purchased from Selleck
Method ELISA
Cell Lines HeLa cells
Concentrations 1 μM
Incubation Time
Results Treatment of infected cells with kinase inhibitors directed at Akt (MK-2206), MEK(PD 98059), PKC(CEC), or Pim family kinases identified a dominant role for Pim family kinases in the release of IL-8 from Salmonella-infected epithelial cells.

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Source FASEB J, 2013, 27, 1644-56. MK-2206 2HCl purchased from Selleck
Method Clonogenic growth assay
Cell Lines U2OS cells
Concentrations 1 μM
Incubation Time 9 d
Results Specific inhibition of PKB activity using MK-2206 or triciribine also significantly reduced cell growth, although to a lesser extent compared to PI-103, suggesting that both the PKB and mTOR pathways are important for anchorage-dependent growth.

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Rating
Source Gynecol Oncol, 2011, 123, 13-8. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines ovarian cancer cell lines
Concentrations 1-6 μM
Incubation Time 1 h/72 h
Results Activation of pAKT by IGF-1 in the low-grade cell line HOC-7 was blocked by the AKT inhibitor MK-2206.

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Source J Cell Biochem, 2011, 112, 924–932. MK-2206 2HCl purchased from Selleck
Method Confocal microscopy
Cell Lines platelets
Concentrations 1μM
Incubation Time
Results Upon treatment with increasing concentrations of AEA from 0.1 to 10 mM (Fig. B–D) platelets were fully fluorescently marked as compared to control (Fig. A) and the increase in DAF 2 fluorescence intensity appears to be dose-dependent. In agreement with data shown in Figure 4, SR1(Fig. E) and MK2206 (Fig. F) abolished fluorescence intensity induced by AEA, while LY294002 (Fig. 5G) was less potent.

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Rating
Source J Cell Biochem, 2011, 112, 924–932. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines platelets
Concentrations 1 μM
Incubation Time
Results eNOSser1177 phosphorylation was greatly reduced by LY294002 and cancelled by MK2206 but it was not modified by platelet pretreatment with EGTA or BAPTA/AM.

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Rating
Source J Cell Biochem, 2011, 112, 924–932. MK-2206 2HCl purchased from Selleck
Method Nitriter+Nitrate(NOX) measurement, cGMP detection
Cell Lines platelets
Concentrations 1 μM
Incubation Time 1 min
Results As shown in Figure 4 SR1 significantly reduced both NOx and cGMP formation, while SR2 failed to affect these parameters.

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Source Radiat Oncol, 2009, 4, 43. MK-2206 2HCl purchased from Selleck
Method Western blot, clonogenic survival assay
Cell Lines U87MG cells
Concentrations 1 μM
Incubation Time 1 h
Results Akt inhibitor MK-2206 showed similar effect. MK-2206 is a potent allosteric Akt inhibitor with IC50 at 8 nm, 2 mM, 65 mM for Akt1, Akt2 and Akt3 respectively. U87MG cells were preincubated with 1 μM MK-2206 for 1 hr, followed by irradiation at 0 - 9 Gy. As shown in Fig C, MK-2206 treatment abolished IR-induced Akt phosphorylation. Moreover, treatment with MK-2206 also increased the radiosensitivity of U87MGcells (Fig. D)

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Rating
Source Dr. Zhang of Tianjin Medical University. MK-2206 2HCl purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-10 nM
Incubation Time 3 h
Results Breast cancer cells were serum starved for 24 h, pretreated with the indicated concentrations of MK-2206 for 3 h, and then treated with 100ng/ml EGF for 15 min.

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Source Biochim Biophys Acta, 2012, 1823, 987-96. MK-2206 2HCl purchased from Selleck
Method Immunofluorescence
Cell Lines HC11 cells
Concentrations 10 µM
Incubation Time 1 h
Results whole ADRP levels, estimated by Western blot , decreased only in the presence of MK -2206 and LY294002. In most cases, ADRP decorated the surface of small lipid droplets and appeared as little patches on large cytoplasmic lipid droplets. With the exception of SP600125, which induced a strong ADRP coating of almost all cytoplasmic lipid droplets (although this inhibitor did not increase ADRP synthesis), variation in the distribution of ADRP at the surface of lipid droplet was difficult to estimate, notably because the signal was faint and uneven.

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Rating
Source MK-2206 2HCl purchased from Selleck
Method Western blot analysis
Cell Lines MCF-7 cells
Concentrations 0 nM/100 nM/250 nM/1000 nM
Incubation Time 24 h
Results The effect of MK-2206 on the serine 473 phosphorylation mark of AKT 1 was uneven and did not correlate with inhibition of AKT activity, but the AKT1 mutant cells maintained higher levels of AKT1 serine 473 phosphorylation with increasing concentrations of MK-2206. Of note, MK-2206 completely inhibited AKT2 activation at 100 nM, a concentration where PIK3CA E545K mutant, but not AKT1 mutant cells were already strongly growth inhibited. MK-2206 treatment up to 1 μM did not have strong effects on other protein biomarkers such as ribosomal protein S6, ev en though growth was suppressed by approximately 80% in MCF-7 cells at this concentration.

文献中の引用 (159)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
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