Pictilisib (GDC-0941)

For research use only. Not for use in humans.

目录号:S1065 别名: RG7321

Pictilisib (GDC-0941) Chemical Structure

CAS No. 957054-30-7

Pictilisib (GDC-0941, RG7321) 是一种有效的PI3Kα/δ抑制剂,在无细胞试验中IC50为 3 nM,对p110β (11倍)和p110γ (25倍)具有适度的选择性。Pictilisib (GDC-0941) 可诱导自噬和凋亡。Phase 2。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1972.48 现货
RMB 986.88 现货
RMB 1390.74 现货
RMB 3026.17 现货
RMB 7926.11 现货
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客户使用Selleck生产的Pictilisib (GDC-0941)发表文献339篇:

产品安全说明书

PI3K抑制剂选择性比较

生物活性

产品描述 Pictilisib (GDC-0941, RG7321) 是一种有效的PI3Kα/δ抑制剂,在无细胞试验中IC50为 3 nM,对p110β (11倍)和p110γ (25倍)具有适度的选择性。Pictilisib (GDC-0941) 可诱导自噬和凋亡。Phase 2。
靶点
p110α [1]
(Cell-free assay)
p110δ [1]
(Cell-free assay)
p110β [1]
(Cell-free assay)
p110γ [1]
(Cell-free assay)
mTOR [1]
(Cell-free assay)
3 nM 3 nM 33 nM 75 nM 0.58 μM(Ki app)
体外研究

GDC-0941也等效作用于PI3Kα和 PI3Kδ和PI3Kα突变型E545-K和H1047-R,也选择性作用于PI3Kβ(10倍)和 PI3Kγ(25倍), 选择性更高地作用于PI3K II, III, 和IV类成员,包括, C2β, Vps34, DNA-PK和mTOR。GDC-0941 作用于U87MG, PC3, 和 MDA-MB-361 细胞,有效抑制Akt磷酸化,IC50分别为46 nM, 37 nM,和 28 nM。GDC-0941抑制U87MG, A2780, PC3, 和MDA-MB-361细胞增殖,IC50分别为 0.95 μM, 0.14 μM, 0.28 μM, 和0.72 μM。[1]GDC-0941处理,有效抑制对Trastuzumab敏感和不敏感的HER2扩增细胞增殖,IC50为149-944 nM,与 Trastuzumab敏感性无关。GDC-0941抑制含PIK3CA突变的HER2扩增的细胞增殖,IC50<500 nM, 且有效抑制抗trastuzumab 的HER2 扩增乳腺癌细胞增殖和活力。[2]GDC-0941 显著抑制HCT116, DLD1和 HT29细胞生长,GI50分别为1081 nM, 1070 nM 和157 nM。[4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 M3zmXGtqdmG|ZTDBd5NigQ>? NHS2coMyKGh? NH7INmJFVVOR MljCTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCSSUPLJJAyOTCmZXz0ZUBmgHC{ZYPz[YQhcW5iU3[5JINmdGy|IHPv[ZhxemW|c3nu[{BxQDWjbIDoZUB4cXSqIFnDOVAhd2ZiMD6wNFMh|ryP M4f4UFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
Sf9 NFfKUJZMcW6jc3WgRZN{[Xl? MlLtNUBp MoSySG1UVw>? MkixTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCSSUPLJJAyOTCkZYThJGgyODR5LWKgcZV1[W62IHX4dJJme3OnZDDpckBU\jliY3XscJMh[2:neIDy[ZN{cW6pIIC4OYFteGijIIfpeIghUUN3MDDv[kAxNjByMzFOwG0> M{[5U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
Sf9 MmLXT4lv[XOnIFHzd4F6 Mlm3NUBp M3\wcWROW09? NX\GWYUxUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDQTVNMKHBzMUDi[ZRiKEV3NEWtT{BufXSjboSg[ZhxemW|c3XkJIlvKFOoOTDj[YxteyClb3X4dJJme3OrbnegdFg2[WyyaHGge4l1cCCLQ{WwJI9nKDBwMECzJO69VQ>? NX;PbGpvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
Sf9 NGeyWnBMcW6jc3WgRZN{[Xl? MXuxJIg> M4nYTWROW09? MlzoTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCSSUPLJJAyOTCkZYThJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiY3;lfJBz\XO|aX7nJJA5PWGucHjhJJdqfGhiSVO1NEBw\iByLkCzN{DPxE1? NV;tZWJHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
Sf9 MkfzT4lv[XOnIFHzd4F6 MmXqNUBp M4HQTGROW09? NX24VHZnUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDQTVNMKHBzMUDhcJBp[SCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJINw\XiycnXzd4lv\yCyOEXhcJBp[Q>? M1q5WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
MDA-MB-361 NGHLXHhHfW6ldHnvckBCe3OjeR?= Mn\SNkBp MnPqSG1UVw>? NIHSVWNKdmirYnn0bY9vKG:oIFHreEBU\XJ2N{OgdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGwIF3ERU1OSi1|NkGgZ4VtdHNid3n0bEBRUUt|Q1GgSVU1PS2NIH31eIF1cW:wIIfpeIghUUN3MDDv[kAxNjB{ODFOwG0> M1f5WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
PC3 NUn3WGYxTnWwY4Tpc44hSXO|YYm= MX6yJIg> MV3EUXNQ M4jncGlvcGmkaYTpc44hd2ZiQXv0JHNmejR5MzDwbI9{eGixconsZZRqd25iaX6gVHRGVi2wdXzsJIh2dWGwIGDDN{Bk\WyuczD3bZRpKEmFNUCgc4YhOC5yM{eg{txO M3m1UFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
U87MG NIPrR3BHfW6ldHnvckBCe3OjeR?= NF;zRlQzKGh? MUHEUXNQ MlPQTY5pcWKrdHnvckBw\iCDa4SgV4VzPDd|IIDoc5NxcG:{eXzheIlwdiCrbjDQWGVPNW63bHygbJVu[W5iVUi3UWch[2WubIOge4l1cCCLQ{WwJI9nKDBwMES2JO69VQ>? NHLrT4E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe1OFY2PCd-MUi3OVQ3PTR:L3G+
MDA-MB-361 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIC2U|c6PiCq MXvEUXNQ NHH2fGJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3ERU1OSi1|NkGgZ4VtdHNid3n0bEBRUUt|Q1GgSVU1PS2NIH31eIF1cW:wIIfpeIghUUN3MDDv[kAxNjd{IN88US=> NWn0WpRvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
A2780 MnX0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXCc|g6PiCq NIHvdldFVVOR NHvURotCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFGyO|gxKGOnbHzzJJdqfGhiUFnLN2NCKGGwZDDQWGVPKG23dHH0bY9vKHerdHigTWM2OCCxZjCwMlE1KM7:TR?= MkfNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
PC3 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17pWFk3KGh? MXTEUXNQ M4TmbGlEPTB;MD6yPEDPxE1? Mle4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
U87MG MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1mxdVk3KGh? NXnWSW9oTE2VTx?= M1f5fmlEPTB;MD65OUDPxE1? M1\S[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
Sf9 M4\UW2tqdmG|ZTDBd5NigQ>? MnjWN|AhdWmw MoPUSG1UVw>? NI\vc2hKdmirYnn0bY9vKG:oIHj1cYFvKFCLM1vnZY1u[SCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgZY1wfW62IH;mJGFVWCClb37zeY1m\CC5aYToJGlEPTBib3[gNE4xPDJizszN NHXMe2k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkW0PFM1Oid-MkK1OFg{PDJ:L3G+
RAW 264.7 MnvqT4lv[XOnIFHzd4F6 NHvEN4g6OCCvaX6= M4L2dWROW09? Mm\QTY5pcWKrdHnvckBw\iCqdX3hckBRUTONZ3HtcYEh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhSUuWIIDoc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gNE4zQThizszN MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2OEO0Nkc,OjJ3NEizOFI9N2F-
Sf9 M1nIbGtqdmG|ZTDBd5NigQ>? NU\XUHVXOSCq NHTzb3JKdmirYnn0bY9vKG:oIFfTWE1nfXOnZDDoeY1idiC{ZXPvcYJqdmGwdDDQTVNM[mW2YTDlfJBz\XO|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRiU1[5JINmdGy|IIfpeIghUUN3MDDv[kAxNjBzNzFOwG0> MoDuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFUoRjJ|NUSwOlQ2RC:jPh?=
Sf9 MVnLbY5ie2ViQYPzZZk> M1fFS|EhcA>? MlfnTY5pcWKrdHnvckBw\iCJU2St[pV{\WRiaIXtZY4hemWlb33ibY5idnRiUFmzT4RmdHSjIHX4dJJme3OnZB?= NXPLUYhORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFA3PDVpPkKzOVQxPjR3PD;hQi=>
Sf9 MofTT4lv[XOnIFHzd4F6 NWDMSWl{OSCq MorWTY5pcWKrdHnvckBw\iCJU2St[pV{\WRiaIXtZY4hemWlb33ibY5idnRiUFmzT4didW2jIHX4dJJme3OnZB?= NVOxRWhvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFA3PDVpPkKzOVQxPjR3PD;hQi=>
Sf9 M1ntO2tqdmG|ZTDBd5NigQ>? Ml7TNUBp M{DVZ2lvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2tidHCqYTDlfJBz\XO|ZXS= NWjTWGpnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFA3PDVpPkKzOVQxPjR3PD;hQi=>
SKOV3 M3TGZmtqdmG|ZTDBd5NigQ>? NHS5ZpEyKM7:TR?= MVmxJIg> MWfEUXNQ M{PrTWlvcGmkaYTpc44hd2ZiUFmzT4FteGijIHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQXv0JHNmejR5MzDwbI9{eGixconsZZRqd25? MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN4MEO0PEc,OjN|NkCzOFg9N2F-
MCF7 NFLBWFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\pZnBTOSEQvF2= MlTxPVYhcA>? NEfxdIZFVVOR MUfHTVUxRTBwMEewNkDPxE1? MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN4MEO0PEc,OjN|NkCzOFg9N2F-
SKOV3 M3SyVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFfZ[48yKM7:TR?= NUGye5l7QTZiaB?= MkL2SG1UVw>? M17GS2dKPTB;MD6xOFc3KM7:TR?= MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN4MEO0PEc,OjN|NkCzOFg9N2F-
PC3 NVr1UJN5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVXielJ1PzJiaB?= MYnEUXNQ M{DDUWlEPTB;MD6yPEDPxE1? Ml\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEG3NVQoRjJzOUixO|E1RC:jPh?=
MCF7.1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPwO|IhcA>? MnLKSG1UVw>? M17xTWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVPGO{4yKGOnbHzzJIV5eHKnc4PpcochUEWUMjDn[Y5mKHerdHigTWM2OCCxZjCwMlI5KM7:TR?= NUDCNpJvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5PFE4OTRpPkKxPVgyPzF2PD;hQi=>
MCF7-neo/Her2 NHTXNIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfKO2xmPzJiaB?= MX7EUXNQ NV7DO3B6UUN3ME2wMlI6KM7:TR?= MljxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NkK5NFMoRjJ|Nk[yPVA{RC:jPh?=
MCF7-neo/Her2 M13sXmtqdmG|ZTDBd5NigQ>? NInTN|FKdmirYnn0bY9vKG:oIGDJN2tidHCqYTDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hd2ZiQVvUJJBpd3OyaH;yfYxifGmxbjDheEBUPDd|IIfpeIghUUN3MDDv[kAxNjByNzFOwG0> MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ4MkmwN{c,OjN4NkK5NFM9N2F-
PC3 NIDYWGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYC3NkBp MUDEUXNQ NV3EbIZUTUN3ME2wMlM1KM7:TR?= M4TFfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUi1OlM6Lz5{MUm4OVY{QTxxYU6=
MCF7.1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYS3NkBp MnW2SG1UVw>? NUTjepVDSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NjFiY3XscJMh\XiycnXzd4lv\yCSSUPLZYxxcGFibYX0ZY51KHerdHigSWM2OCCxZjCwMlM6KM7:TR?= MoryQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEW2N|koRjJzOUi1OlM6RC:jPh?=
PC3 MmXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF:5bHM4OiCq NIGzd|ZFVVOR MVLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFCFMzDj[YxteyCmZX\pZ4lmdnRiaX6gVHRGViC5aYToJGlEPTBib3[gNE4{QSEQvF2= MoT5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByNUC2OlkoRjJyMEWwOlY6RC:jPh?=
MCF7.1 NVXsPWpsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHjN2wyPzJiaB?= M1S0XmROW09? NV;ZRoVGSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NjFiY3XscJMh\XiycnXzd4lv\yCSSUPLZYxxcGFibYX0ZY51KHerdHigTWM2OCCxZjCwMlM1KM7:TR?= MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODB3ME[2PUc,OjByNUC2Olk9N2F-
MCF7.1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3S1OlczKGh? NHjVN|BGSzVyPUCuO|Ih|ryP NXfmeVl7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCzOFY3PTZpPkKwN|Q3PjV4PD;hQi=>
NCI-H1975 NVPSWFR6S3m2b4TvfIlkKEG|c3H5 NYTt[|NFPzJiaB?= NX\3[mZRUUN3ME2wMlI4KM7:TR?= MnrXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNUm1OFUoRjJ|MEW5OVQ2RC:jPh?=
H460 MkKxR5l1d3SxeHnjJGF{e2G7 NULTe|FyPzJiaB?= M1Lp[WlEPTB;MD64O{DPxE1? NFXyUZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
HT-29 NVHVdVNqS3m2b4TvfIlkKEG|c3H5 MlzSO|IhcA>? M{nwUGlEPTB;MD62OkDPxE1? NHXqOFE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-AKT / AKT / p-FoxO3a / FoxO3a / PUMA; 

PubMed: 29137323     


HCT116 cells were treated with 4μmol/L NVP-BKM120 or 4μmol/L Pictilisib for 24 hours. Indicated protein levels were analyzed by Western blotting.

p-S6RP / S6RP; 

PubMed: 30042442     


Western blot analysis of proteins as indicated in 4T1 cells treated with 1 µM GDC-0941 or vehicle for 24 h. Vinculin was used as a loading control. 

p-4EBP1 / 4EBP1; 

PubMed: 25857298     


Cells were treated with 0.5 μM GDC-0941 for the indicated time course and then collected for Western blot analysis of p-4EBP1. 

p-LRP6 / LRP6; 

PubMed: 25857298     


MDAMB-231, HCC1937 and MCF7 cells were treated with 0.5 µM GDC-0941 for 1 hr, and cell lysates were used for immunoblot analyses.

p-PAK / PAK1 / p-CRAF / RAF / p-MEK / MEK / p-ERK / ERK; 

PubMed: 24327733     


Cells were treated with 1 μM GDC-0941 for the indicated times, and lysates were probed with the indicated antibodies. Independent experiments were performed at least three times, and a representative result is shown.

29137323 30042442 25857298 24327733
Immunofluorescence
p65; 

PubMed: 30042442     


Representative images of immunofluorescent staining of p65 cellular localization in 4T1 cells treated with 1 µM GDC-0941 or vehicle for 24 h. 4T1 cells were cultured alone or co-cultured with RAW264.7 macrophages. Representative images of three independent experiments are shown. 

beta-catenin; 

PubMed: 25857298     


Cells were seeded on coverslips the day before the experiment and treated with 0.5 µM GDC-0941 for 18 hr. The immunofluorescence (IF) of beta-catenin is indicated as red fluorescence, and double staining with DAPI is blue. Magnification: 400 X for the left three panels. The right panel shows enlarged images from the white squares.

30042442 25857298
Growth inhibition assay
Cell viability; 

PubMed: 27117832     


The viability of the indicated cells treated with increasing concentrations of GDC-0941 (ranging from 70nM to 20 μM) for 72 hours, determined by CellTiter Glo Viability assay. The IC50 concentrations were calculated using GraphPad Prism program. The assay was performed in triplicate, and the error bars represent standard deviations.

27117832
体内研究 在微粒体中,GDC-0941仅有有限的代谢,其口服生物利用度为78%[5]。GDC-0941 每天按 75 mg/kg剂量处理携带人U87MG 恶性胶质移植瘤的雌性NCr无胸腺小鼠,显著抑制生长,肿瘤生长抑制率为 83%。[1]GDC-0941 每天按 150 mg/kg剂量口服处理携带HER2扩增的抗Trastuzumab的MDA-MB-361.1移植瘤 的小鼠,抑制肿瘤生长,且显著延迟肿瘤衰退,与肿瘤中强诱导型凋亡相关。[2] GDC-0941 每天按75 mg/kg剂量处理携带自发性B细胞滤泡性淋巴瘤的PTEN+/-LKB1+/hypo小鼠,持续2周,诱导肿瘤体积下降~40%,伴随着AKT, S6K 和SGK(血清和糖皮质激素蛋白激酶)蛋白激酶的磷酸化被切除。GDC-0941抑制肿瘤细胞增殖,诱导凋亡和抑制中心母细胞数。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

- 合并

闪烁接近检测:

使用p85α调节亚基,使重组人PI3Kα, PI3Kβ, 和PI3Kδ在 Sf9 杆状病毒系统中共表达,在谷胱甘肽-琼脂糖凝胶上进行亲和层析而纯化GST-融合蛋白。重组人 PI3Kγ表达作为单体 GST融合,也想上述相似方法纯化。GDC-0941 溶于DMSO,加到含200 μg硅酸钇(Ysi) 聚赖氨酸SPA 磁珠, 4 mM MgCl2, 1 mM 二硫苏糖醇 (DTT), 1 μM ATP, 0.125 μCi [γ-33P]-ATP, 和4% (v/v) DMSO的20 mM Tris-HCl (pH 7.5)上,总体积为 50 μL。PI3Kα (5 ng), PI3Kβ(5 ng), PI3Kδ(5 ng), 或PI3Kγ(5 ng)的重组GST-融合 ,加到实验混合物中,开始激酶反应。在室温下温育1小时后, 加入150 μL PBS终止反应。混合物在2000 rpm 转速下离心2分钟,然后使用Wallac Microbeta计数器读数。在 MDL Assay Explorer系统中使用S型,剂量-反应曲线,计算进行至少2次独立重复实验,取平均值,作为IC50值。
细胞实验:

[2]

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  • Cell lines: SKBR-3, BT474-M1, AU-565, HCC-1419, ZR75-30, KPL-4, JIMT-1, BT474-EEI, HCC-1954, MCF-7, CALU-3, SKOV-3, 和MKN-7
  • Concentrations: 溶于DMSO,终浓度为~10 μM
  • Incubation Time: 48,和72小时
  • Method:

    使用不同浓度 GDC-0941处理细胞48,和 72小时。通过CellTiter-Glo Luminescent细胞活性检测实验测定细胞增殖/活力。通过Western Blot分析pAKT (Ser473), cleaved caspase-3, 和cleaved PARP通过 Caspase-Glo 3/7实验和细胞死亡检测 ELISAplus 实验分别测定caspase 3/7活性, 和凋亡。


    (Only for Reference)
动物实验:

[2]

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  • Animal Models: 移植MDA-MB-361.1细胞的NCR裸鼠, 皮下移植BT474-M1 细胞的SCID, C.B-17/IcrHsd-Prkdcscid 小鼠
  • Dosages: ~150 mg/kg/day
  • Administration: 口服饲喂
    (Only for Reference)