MK-2206 2HCl

Catalog No.S1078

MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. Phase 2.

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MK-2206 2HCl Chemical Structure

MK-2206 2HCl Chemical Structure
Molecular Weight: 480.39

Validation & Quality Control

Product Use Citation(170)

Customer Product Validation(18)

Quality Control & MSDS

Related Compound Libraries

MK-2206 2HCl is available in the following compound libraries:

Akt Inhibitors with Unique Features

  • Selective Akt Inhibitor

    CCT128930 AKT2-selective, IC50=6 nM.

  • Most Potent Akt Inhibitor

    AZD5363 Akt1, IC50=3 nM; Akt2, IC50=8 nM; Akt3, IC50=8 nM.

  • Akt Inhibitor in Clinical Trial

    Perifosine (KRX-0401) Phase III fro relapsed and refractory multiple myeloma.

  • Newest Akt Inhibitor

    AZD5363 Potent inhibitor of all isoforms of Akt (Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM, similar to P70S6K/PKA and lower activity towards ROCK1/2.

Product Information

  • Compare Akt Inhibitors
    Compare Akt Products
  • Research Area
  • Inhibition Profile
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. Phase 2.
Targets Akt1 [1]
(Cell-free assay)
Akt2 [1]
(Cell-free assay)
Akt3 [1]
(Cell-free assay)
IC50 8 nM 12 nM 65 nM
In vitro 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 DescriptionPMID
NCI-H292NYrYPXRmS3m2b4TvfIlkKEG|c3H5MVizJO69VQ>?NFvrSYU4OiCqMXPEUXNQM37MOGlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wMWiyNFU4OTB4OR?=
A431M1H3emtqdmG|ZTDBd5NigQ>?M3TkTFUh|ryPM4OzOlUhcA>?NEDZN3RFVVORNVPNe2ZOW3WycILld5NmeyC2aHWgd4lodmGuaX7nJI9nKEGtdDDhcoQhTXKtNU\Bd4I3OjB3N{GwOlk>
HepG2NF20bplEgXSxdH;4bYMhSXO|YYm=MVOxNEDPxE1?NUToR5lWOjRiaB?=M4OwcWROW09?MoDDV4Vve2m2aYrld{Bz\XOrc4ThcpQh[2WubIOgeI8hfGinIHP5eI91d3irYzDl[oZm[3Rib3[gd49z[W[nbnniM4HLe|IyOjB3OUK1
Sk-Hep1NVHyXokxS3m2b4TvfIlkKEG|c3H5MVqxNEDPxE1?Mn:xNlQhcA>?MoH4SG1UVw>?NXnIfZJHW2Wwc3n0bZpmeyC{ZYPpd5RidnRiY3XscJMhfG9idHjlJIN6fG:2b4jpZ{Bm\m[nY4Sgc4Yhe2:{YX\lcoljM3flV|IyOjB3OUK1
OCUT1 cells harbored PIK3CA (H1047R+/+)NXzUNYFxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYmzJO69VQ>?NIS0ZoM2KGR?NFnnOHVFVVORMYnJR|UxRTBwMUSg{txONEDZVXQzOTJ6OUK2Oy=>
K1 cells harbored PIK3CA (E542K+/+)M{TX[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkDVN{DPxE1?NF3wcWM2KGR?M2XDVWROW09?MlLjTWM2OD1yLkWyJO69VQ>?NFTxeGgzOTJ6OUK2Oy=>
FTC133 cells harbored PTEN (allele deletion and R130+)M{K4[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NF3zepA{KM7:TR?=NY[2XpR7PSCmM4DBOWROW09?M3\FOGlEPTB;MD6xPEDPxE1?M13BPVIyOjh7Mk[3
C643 cells harbored HRAS (G13R+/−)M1Pz[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mm\JN{DPxE1?NUG3OHNWPSCmNEHYNpNFVVORMXjJR|UxRTBwMkeg{txONIT5[WMzOTJ6OUK2Oy=>
Hth7 cells harbored NRAS (Q61R+/−)MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIfF[2I{KM7:TR?=M{P1elUh\A>?NHHmXVVFVVORNFfCXHhKSzVyPUSuOUDPxE1?NVPvdVZUOjF{OEmyOlc>
TPC1 cells harbored RET/PTC1 rearrangementMWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGnXW24{KM7:TR?=M2PDd|Uh\A>?NYnhOVFFTE2VTx?=MXPJR|UxRTBwNUmg{txOM4\GRlIyOjh7Mk[3
Hth74NFT3[WNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MV:zJO69VQ>?NX3mNFE3PSCmM2jufGROW09?MmrETWM2OD1{LkG5JO69VQ>?NIrDbG4zOTJ6OUK2Oy=>
KAT18NVHwbmp5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUXvelQ{OyEQvF2=NHXnZYM2KGR?M2nVRWROW09?M1LafGlEPTB;ND62NkDPxE1?MmDxNlEzQDl{Nke=
SW1736MnK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NUnQUIQzOTByIN88US=>M1zlPFUh\A>?NXrPO2NnTE2VTx?=NH;R[mpKSzVyPUS3MlU3KM7:TR?=NXHifW82OjF{OEmyOlc>
WROM4TWOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MV6xNFAxKM7:TR?=MXm1JIQ>M4TpTGROW09?MV7JR|UxRjFyMECg{txOMXWyNVI5QTJ4Nx?=
TAD2Mkf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWLkVXpEOTByMDFOwG0>M1TTb|Uh\A>?NXS5NG1LTE2VTx?=M4n1ZmlEPTB-MUCwNEDPxE1?NIjnU4kzOTJ6OUK2Oy=>
LN229NUjQ[mFkSXCxcITvd4l{KEG|c3H5MX[wMlUh|ryPMXS2NEBpMV7EUXNQNGX0RpVCfWevZX70d{BieG:ydH;n[Y5q[yCnZn\lZ5R{KG:oIHfl[ol1cW6rYh?=M37iO|IzODV5OUG0
T98GNY[xTVVoSXCxcITvd4l{KEG|c3H5MUewMlUh|ryPMXq2NEBpM{DadmROW09?MXrBeYdu\W62czDhdI9xfG:pZX7pZ{Bm\m[nY4TzJI9nKGenZnn0bY5q[g>?MoTDNlIxPTd7MUS=
HC11M2PlcWZ2dmO2aX;uJGF{e2G7NYXIN|dsOTBizszNMmTxNlQhcA>?NUmxd4hVTE2VTx?=NE\u[JlKdmirYnn0d{DPui2lYYPlbY4h[W6mIFHEVnAhe3mwdHjld4l{M{GxNFIzPDJ4NkKx
MOLT-4MWDDfZRwfG:6aXOgRZN{[Xl?MVyxNEDPxE1?NFL2dYo1QCCqNFP5VIFFVVORNEHWRnpKSzVyPUGuO-KBkc7:TR?=M1vUeVIzPjF2MkSz
CEM-RNHrLRVREgXSxdH;4bYMhSXO|YYm=MVOxNEDPxE1?NX3Md|VjPDhiaB?=NXezdI5TTE2VTx?=NE\NWXZKSzVyPUOuN-KBkc7:TR?=NWPWS2VGOjJ4MUSyOFM>
CEM-SNGDpO41EgXSxdH;4bYMhSXO|YYm=NIrkfYoyOCEQvF2=NYe1Sos6PDhiaB?=NHG3XVRFVVORNWTI[GRXUUN3ME21MlHjiIoQvF2=MmfkNlI3OTR{NEO=
MOLT-4M1nvcWZ2dmO2aX;uJGF{e2G7NIjDeZEyOCEQvF2=M2roflI1KGh?NGjTUVdFVVORM4SyVGJtd2OtczDj[YxteyCrbjD0bIUhTzBxR{GgdIhie2Vib3[geIhmKGOnbHygZ5lkdGV?NVX1dm9SOjJ4MUSyOFM>
MOLT-4NULC[JRLTnWwY4Tpc44hSXO|YYm=NIHPRYQ16oDLzszNNF;ONmg1KGh?MYPEUXNQMkTqTY5kemWjc3XzJJRp\SCjbX;1cpQhd2ZiY3zlZZZm\CCOQ{PBM2ItKGFid3XscE1me3SjYnzpd4hm\CCjdYTvdIhi\3libXHyb4VzNVv2VIdzOjJ4MUSyOFM>
CEM-RNFLiOVdHfW6ldHnvckBCe3OjeR?=M2W4cVTjiIoQvF2=MYK0JIg>NXe5XY9pTE2VTx?=MmXhTY5kemWjc3XzJJRp\SCjbX;1cpQhd2ZiY3zlZZZm\CCOQ{TBM2ItKGFid3XscE1me3SjYnzpd4hm\CCjdYTvdIhi\3libXHyb4VzMX[yNlYyPDJ2Mx?=
CEM-SMX\GeY5kfGmxbjDBd5NigQ>?Mor0OQKBkc7:TR?=M2TjTFQhcA>?M4DDRWROW09?Mn\4TY5kemWjc3XzJJRp\SCjbX;1cpQhd2ZiY3zlZZZm\CCOQ{XBM2ItKGFid3XscE1me3SjYnzpd4hm\CCjdYTvdIhi\3libXHyb4VzNIf6PFgzOjZzNEK0Ny=>
HepG2 cellMW\LbY5ie2ViQYPzZZk>NYHNOpd7OjBizszNNEnlbYozPCCqNWHqR|ZnTE2VTx?=M3;ENWRwf26{ZXf1cIF1\XNidHjlJJBpd3OyaH;yfYxifGmxbjDv[kBCU1R?MorxNlM4QTd|MUm=
HepG2 cellNGfrZ3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoL6N|Ah|ryPNFHXS5MzPCCqNEfG[5lFVVORNXfQUFR4UW6qaXLpeJMh[2WubDDndo94fGh?MWmyN|c6PzNzOR?=
HepG2 cellMVHBdI9xfG:|aYOgRZN{[Xl?MlHVNlAh|ryPM2TCNlI1KGh?M3LKXmROW09?NX7hVIE5UW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=MUiyN|c6PzNzOR?=
GEOMonXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NVPzPW9xPTByIH7NM2PPbFczKGh?MVvEUXNQMXjJcohq[mm2czDj[YxtKGe{b4f0bC=>MXGyOFU5OTJ|MR?=
CNE-1MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmTCNVAh|ryPM3;SR|k3KGh?NFjzZZNFVVORMWXJR|UxRTJwOU[g{txOMVuyOVM{Pjl{NR?=
CNE-2NYjRUmVUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUexNEDPxE1?NHj5[2k6PiCqMmTWSG1UVw>?NIfhdWRKSzVyPUSuOVMh|ryPMWiyOVM{Pjl{NR?=
HONE-1NFLGSYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIDPOXcyOCEQvF2=NI\PR4k6PiCqM{TRXWROW09?NXjuPGFRUUN3ME2zMlM4KM7:TR?=MYmyOVM{Pjl{NR?=
SUNE-1NFHlepRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoHINVAh|ryPMk\GPVYhcA>?NY[zb4RPTE2VTx?=NUTTWVBtUUN3ME2wMlUzKM7:TR?=MXGyOVM{Pjl{NR?=
CNE-2NXiyV2NrTnWwY4Tpc44hSXO|YYm=M2HQbVExKM7:TR?=MkG4OFghcA>?NIHONW5FVVORM2HRcmlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZZQhTzF?M33Qd|I2OzN4OUK1
HONE-1Mn;rSpVv[3Srb36gRZN{[Xl?NX3zboZvOTBizszNMmjKOFghcA>?NWHGTnZETE2VTx?=M{T4S2lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZZQhTzF?NWrhVHFOOjV|M{[5NlU>
NEC8MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlT3TWM2OD1yLkC5OlUyKM7:TR?=MonBV2FPT0WU
P12-ICHIKAWAM3jPZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NUPYSG9FUUN3ME2wMlEyPjJizszNNEOzWVJUSU6JRWK=
MDA-MB-175-VIIMUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Ml;yTWM2OD1yLkGzO|M5KM7:TR?=MljiV2FPT0WU
AsPC-1NUT4XpBwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlPzTWM2OD1yLkKyNVIzKM7:TR?=MYnTRW5ITVJ?
T47DNXntb2VXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWjQN49lUUN3ME2wMlI5OjVizszNMUTTRW5ITVJ?
HHM2XRd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoTSTWM2OD1yLkOwNlg{KM7:TR?=NGi5cnRUSU6JRWK=
MOLT-16NUTEW|R{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH\jbVZKSzVyPUCuN|A{OiEQvF2=M3LZcXNCVkeHUh?=
ES5M{m1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVrudW1CUUN3ME2wMlM1PDV3IN88US=>NV7zTYMzW0GQR1XS
RS4-11M3W4emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mk[5TWM2OD1yLkO0OlEh|ryPMljYV2FPT0WU
KARPAS-45NFzvdW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NFvqbGpKSzVyPUCuN|c{OjFizszNM3rkdXNCVkeHUh?=
NCI-H720MnjoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXHJR|UxRTBwM{e2O|kh|ryPMWjTRW5ITVJ?
H9NEf2Z4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MUHJR|UxRTBwM{i4PFMh|ryPMn\CV2FPT0WU
EFM-19NH;LPIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXHTOIppUUN3ME2wMlQ1ODFizszNNYXEUnRFW0GQR1XS
SBC-1M2LGN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mmi1TWM2OD1yLkS0NFM2KM7:TR?=M4HTZXNCVkeHUh?=
A4-FukMXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUfJR|UxRTBwNE[4Olgh|ryPNES5UpVUSU6JRWK=
NCI-H1563MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NF\1WJdKSzVyPUCuOFgyQDlizszNMXPTRW5ITVJ?
HCC1419MoOwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NVXMT2tJUUN3ME2wMlQ5QDl{IN88US=>NFXYSG9USU6JRWK=
H-EMC-SSNXv5ZnIzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NEHSdpJKSzVyPUCuOFk6OzlizszNM4W5OXNCVkeHUh?=
BHT-101M33vSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnLFTWM2OD1yLkWyPVYyKM7:TR?=MUPTRW5ITVJ?
IGROV-1NX;ReFA1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFz5cpFKSzVyPUCuOVUzPDlizszNM1;3OXNCVkeHUh?=
HGC-27MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGH3NJNKSzVyPUCuOVY4QDNizszNNGewdJZUSU6JRWK=
MDA-MB-361NGrUZ2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{X3dWlEPTB;MD61O|c3OSEQvF2=M{HobHNCVkeHUh?=
KE-37M4r0[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYPXdHg4UUN3ME2wMlU5OjZizszNMmDCV2FPT0WU
HCC70NHnj[YJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXTuS2NPUUN3ME2wMlU6QDJ5IN88US=>MUPTRW5ITVJ?
LNCaP-Clone-FGCMoHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWfwPXNjUUN3ME2wMlYyODR6IN88US=>MUfTRW5ITVJ?
HAL-01M1LndGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmLHTWM2OD1yLk[yNVMh|ryPMl\EV2FPT0WU
HTNHWy[XZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MlLxTWM2OD1yLk[zNlM6KM7:TR?=MWjTRW5ITVJ?
MDA-MB-415M4njdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1LMeGlEPTB;MD62N|YzPiEQvF2=M2ey[HNCVkeHUh?=
NOS-1M4jVWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NX\iO4dxUUN3ME2wMlY{PzJ|IN88US=>NXHQRolkW0GQR1XS
DU-145NV7WW4t1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX;JWWNVUUN3ME2wMlY1PzR3IN88US=>MUnTRW5ITVJ?
OCUB-MNVLp[5h6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoLiTWM2OD1yLkewPVY3KM7:TR?=NF[0dIZUSU6JRWK=
VA-ES-BJNUHs[WxlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHK4TndKSzVyPUCuO|MxOjVizszNMlO3V2FPT0WU
J-RT3-T3-5M2P4Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGfydlBKSzVyPUCuO|Q1ODNizszNMmXlV2FPT0WU
MOLT-4NHzvOHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4DuRmlEPTB;MD64NFU5OiEQvF2=NGfQTWxUSU6JRWK=
NB7NYnxVFJYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWPJR|UxRTBwOEK0NVEh|ryPNYLlOFRSW0GQR1XS
L-363MoTiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYTOTHdIUUN3ME2wMlg{PDR{IN88US=>MofBV2FPT0WU
NKM-1M1nP[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVL5OWk3UUN3ME2wMlg3OjV|IN88US=>MUDTRW5ITVJ?
HOP-92NIG4eZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWfJR|UxRTBwOEeyNlMh|ryPMlXwV2FPT0WU
OAW-42M{LzOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlvGTWM2OD1yLki4O|Ih|ryPNFLVXFRUSU6JRWK=
HuO9M4m5TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnTLTWM2OD1yLkmyO|UyKM7:TR?=Ml3LV2FPT0WU
MFE-280NUPhOJlHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYfJR|UxRTBwOU[0OlUh|ryPMnnIV2FPT0WU
EM-2NFrB[mVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoDSTWM2OD1yLkm3PVM6KM7:TR?=NGPkd4ZUSU6JRWK=
NCI-H520NH7URXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWC3cGtSUUN3ME2wMlk5PTl{IN88US=>NG\IOnRUSU6JRWK=
LB2241-RCCMX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXXJR|UxRTBwOUm3N|Qh|ryPNF7ZSYNUSU6JRWK=
SK-NEP-1NHLIPVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1raN2lEPTB;MT6xOFQ5PSEQvF2=NXm5bll7W0GQR1XS
LXF-289M4X4cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NX\tSllUUUN3ME2xMlE4OTV4IN88US=>M2iwdHNCVkeHUh?=
EPLC-272HNXroNnA4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX3XbYhMUUN3ME2xMlE4OjV4IN88US=>NW\McYxRW0GQR1XS
COLO-684MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NEHifHRKSzVyPUGuNlM4OjVizszNMX;TRW5ITVJ?
ES1NGG2ZoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4TyRmlEPTB;MT6yOFA3PSEQvF2=MmK4V2FPT0WU
DOHH-2MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4fvbmlEPTB;MT6yPFIxOyEQvF2=NFz5VndUSU6JRWK=
CTB-1Mk\RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFrvWlZKSzVyPUGuNlg6QSEQvF2=NXLNSHZQW0GQR1XS
G-401NGnS[VRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYLJR|UxRTFwMkm3PVUh|ryPMljCV2FPT0WU
LoVoNEXQZVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYrJR|UxRTFwM{K1N|Qh|ryPM374XnNCVkeHUh?=
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... Click to View More Cell Line Experimental Data

In vivo 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]
Features The first allosteric small molecule inhibitor of Akt to enter clinical development.

Protocol(Only for Reference)

Kinase Assay: [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.

Cell Assay: [2]

Cell lines A431, HCC827, NCI-H292, NCI-H358, NCI-H23, NCI-H1299, Calu-6 and NCI-H460 cells
Concentrations 0, 0.3, 1 and 3 μM
Incubation Time 72 or 96 hours
Method 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.

Animal Study: [2]

Animal Models SK-OV-3, NCI-H292, HCC70, PC-3, and NCI-H460 models in male CD1-nude mice
Formulation Formulated in 30% Captisol
Dosages 120 mg/kg
Administration Orally administered

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
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

References

[1] Yan L, AACR Annual Meeting 2009: Abstract Number: DDT01-1.

[2] Hirai H, et al. Mol Cancer Therapy, 2010, 9(7), 1956-1967.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-04-16)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01802320 Active, not recruiting Colon Mucinous Adenocarcinoma|Colon Signet Ring Cell Adenocarcinoma|Rectal Mucinous Adenocarcinoma|Rectal Signet Ring Cell Adenocarcinoma|Recurrent  ...more Colon Mucinous Adenocarcinoma|Colon Signet Ring Cell Adenocarcinoma|Rectal Mucinous Adenocarcinoma|Rectal Signet Ring Cell Adenocarcinoma|Recurrent Colon Carcinoma|Recurrent Rectal Carcinoma|Stage IIIA Colon Cancer|Stage IIIA Rectal Cancer|Stage IIIB Colon Cancer|Stage IIIB Rectal Cancer|Stage IIIC Colon Cancer|Stage IIIC Rectal Cancer|Stage IVA Colon Cancer|Stage IVA Rectal Cancer|Stage IVB Colon Cancer|Stage IVB Rectal Cancer National Cancer Institute (NCI) March 2013 Phase 2
NCT01783171 Recruiting Pancreatic Adenocarcinoma|Recurrent Pancreatic Carcinoma|Stage III Pancreatic Cancer|Stage IV Pancreatic Cancer|Unresectable Pancreatic Carcinoma National Cancer Institute (NCI) January 2013 Phase 1
NCT01776008 Active, not recruiting Estrogen Receptor Positive|HER2/Neu Negative|Recurrent Breast Carcinoma|Stage IIA Breast Cancer|Stage IIB Breast Cancer|Stage IIIA Breast Cancer|St  ...more Estrogen Receptor Positive|HER2/Neu Negative|Recurrent Breast Carcinoma|Stage IIA Breast Cancer|Stage IIB Breast Cancer|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer National Cancer Institute (NCI) January 2013 Phase 2
NCT01859182 Withdrawn Adenocarcinoma of the Gallbladder|Adenocarcinoma With Squamous Metaplasia of the Gallbladder|Adult Primary Cholangiocellular Carcinoma|Advanced Adu  ...more Adenocarcinoma of the Gallbladder|Adenocarcinoma With Squamous Metaplasia of the Gallbladder|Adult Primary Cholangiocellular Carcinoma|Advanced Adult Primary Liver Cancer|Cholangiocarcinoma of the Extrahepatic Bile Duct|Localized Unresectable Adult Primary Liver Cancer|Metastatic Extrahepatic Bile Duct Cancer|Recurrent Adult Primary Liver Cancer|Recurrent Extrahepatic Bile Duct Cancer|Stage II Gallbladder Cancer|Stage IIIA Gallbladder Cancer|Stage IIIB Gallbladder Cancer|Stage IVA Gallbladder Cancer|Stage IVB Gallbladder Cancer|Unresectable Extrahepatic Bile Duct Cancer National Cancer Institute (NCI) January 2013 Phase 2
NCT01705340 Terminated Adenocarcinoma of the Gastroesophageal Junction|HER2-positive Breast Cancer|Male Breast Cancer|Recurrent Breast Cancer|Recurrent Esophageal Cancer|  ...more Adenocarcinoma of the Gastroesophageal Junction|HER2-positive Breast Cancer|Male Breast Cancer|Recurrent Breast Cancer|Recurrent Esophageal Cancer|Recurrent Gastric Cancer|Stage IIIC Breast Cancer|Stage IIIC Esophageal Cancer|Stage IIIC Gastric Cancer|Stage IV Breast Cancer|Stage IV Esophageal Cancer|Stage IV Gastric Cancer National Cancer Institute (NCI) September 2012 Phase 1

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Chemical Information

Download MK-2206 2HCl SDF
Molecular Weight (MW) 480.39
Formula

C25H21N5O.2HCl

CAS No. 1032350-13-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 14 mg/mL (29.14 mM)
Water <1 mg/mL (<1 mM)
Ethanol <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.
Chemical Name 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one

Customer Product Validation (18)


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Source Cell, 2015, 160(1-2): 161-76 . MK-2206 2HCl purchased from Selleck
Method Western Blot
Cell Lines Ser78 cells
Concentrations 5 µM
Incubation Time 1 h
Results Two selective AKT inhibitors MK-2206 and GDC-0068, both significantly reduced MKK4 phosphorylation on Ser78 in axons after injury.

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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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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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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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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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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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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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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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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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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 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.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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