Pictilisib (GDC-0941)

Catalog No.S1065 Synonyms: RG7321

For research use only.

Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.

Pictilisib (GDC-0941) Chemical Structure

CAS No. 957054-30-7

Selleck's Pictilisib (GDC-0941) has been cited by 383 publications

Purity & Quality Control

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Biological Activity

Description Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.
Targets
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)
In vitro

GDC-0941 is equipotent against PI3Kα and PI3Kδ as well as PI3Kα mutants E545-K and H1047-R, displaying modest levels of selectivity against PI3Kβ (10-fold) and PI3Kγ (25-fold), and greater levels of selectivity against members of PI3K class II, III, and IV, including C2β, Vps34, DNA-PK, and mTOR. GDC-0941 potently inhibits the phosphorylation of Akt in U87MG, PC3, and MDA-MB-361 cells with IC50 of 46 nM, 37 nM, and 28 nM, respectively. GDC-0941 inhibits the proliferation of U87MG, A2780, PC3, and MDA-MB-361 cells with IC50 of 0.95 μM, 0.14 μM, 0.28 μM, and 0.72 μM, respectively. [1] GDC-0941 treatment potently inhibits the proliferation of both trastuzumab-sensitive and -insensitive HER2-amplified cells with IC50 of 149-944 nM. GDC-0941 inhibits proliferation of HER2-amplified cells that harbor PIK3CA mutations with IC50 of <500 nM, and effectively inhibits both proliferation and viability of HER2-amplified breast cancer cells that are resistant to trastuzumab due to PTEN loss. [2] GDC-0941 significantly inhibits the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. [3] GDC-0941 inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 M4PC[2tqdmG|ZTDBd5NigQ>? MWCxJIg> MUTEUXNQ MVLJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KFCLM1ugdFEyOGSnbIThJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiY3;lfJBz\XO|aX7nJJA5PWGucHjhJJdqfGhiSVO1NEBw\iByLkCwN{DPxE1? M3S1cVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
Sf9 M37FWGtqdmG|ZTDBd5NigQ>? MYqxJIg> NH65b3VFVVOR M1Hn[2lvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiUFmzT{BxOTFyYnX0ZUBJOTB2Nz3SJI12fGGwdDDlfJBz\XO|ZXSgbY4hW2Z7IHPlcIx{KGOxZYjwdoV{e2mwZzDwPFVidHCqYTD3bZRpKEmFNUCgc4YhOC5yMEOg{txO MoDLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
Sf9 NIHp[5ZMcW6jc3WgRZN{[Xl? MWCxJIg> M4S0NGROW09? NEL4fpNKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IGDJN2sheDFzMHLleIEhTTV2NT3LJI12fGGwdDDlfJBz\XO|ZXSgbY4hW2Z7IHPlcIx{KGOxZYjwdoV{e2mwZzDwPFVidHCqYTD3bZRpKEmFNUCgc4YhOC5yMEOg{txO NEDLUWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe1OFY2PCd-MUi3OVQ3PTR:L3G+
Sf9 MUPLbY5ie2ViQYPzZZk> MYexJIg> MVLEUXNQ M3fXOGlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiUFmzT{BxOTFyYnX0ZUBmgHC{ZYPz[YQhcW5iU3[5JINmdGy|IHPv[ZhxemW|c3nu[{BxQDWjbIDoZUB4cXSqIFnDOVAhd2ZiMD6wN|Mh|ryP Ml\NQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
Sf9 NWP0OVQzU2mwYYPlJGF{e2G7 M17lXFEhcA>? MU\EUXNQ Ml7WTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCSSUPLJJAyOTCjbIDoZUBmgHC{ZYPz[YQhcW5iU3[5JINmdGy|IHPv[ZhxemW|c3nu[{BxQDWjbIDoZS=> NFvnUZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe1OFY2PCd-MUi3OVQ3PTR:L3G+
MDA-MB-361 MULGeY5kfGmxbjDBd5NigQ>? NIfDNGEzKGh? MoHPSG1UVw>? MlH2TY5pcWKrdHnvckBw\iCDa4SgV4VzPDd|IIDoc5NxcG:{eXzheIlwdiCrbjDoeY1idiCPRFGtUWIuOzZzIHPlcIx{KHerdHigVGlMO0ODIFW1OFUuUyCvdYTheIlwdiC5aYToJGlEPTBib3[gNE4xOjhizszN NWLxbmt3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
PC3 NE\4d4JHfW6ldHnvckBCe3OjeR?= M3eyU|IhcA>? MWjEUXNQ NGnFb5hKdmirYnn0bY9vKG:oIFHreEBU\XJ2N{OgdIhwe3Cqb4L5cIF1cW:wIHnuJHBVTU5vboXscEBpfW2jbjDQR|Mh[2WubIOge4l1cCCLQ{WwJI9nKDBwMEO3JO69VQ>? MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDd3NE[1OEc,OTh5NUS2OVQ9N2F-
U87MG M1\pNWZ2dmO2aX;uJGF{e2G7 NHXO[mMzKGh? MWnEUXNQ MkXBTY5pcWKrdHnvckBw\iCDa4SgV4VzPDd|IIDoc5NxcG:{eXzheIlwdiCrbjDQWGVPNW63bHygbJVu[W5iVUi3UWch[2WubIOge4l1cCCLQ{WwJI9nKDBwMES2JO69VQ>? NIOyPYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe1OFY2PCd-MUi3OVQ3PTR:L3G+
MDA-MB-361 MoSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fwWlk3KGh? MUPEUXNQ NXS5O29sSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvM{[xJINmdGy|IIfpeIghWEmNM1PBJGU2PDVvSzDteZRifGmxbjD3bZRpKEmFNUCgc4YhOC55MjFOwG0> NWHtUXY{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
A2780 NX6xZ29VT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1Hadlk3KGh? NUHCSFdbTE2VTx?= NFPJOFZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFGyO|gxKGOnbHzzJJdqfGhiUFnLN2NCKGGwZDDQWGVPKG23dHH0bY9vKHerdHigTWM2OCCxZjCwMlE1KM7:TR?= NXvFOZBVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
PC3 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;3TVM6PiCq MWfEUXNQ NXjURYprUUN3ME2wMlI5KM7:TR?= MlXxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
U87MG M2DkZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1P5WFk3KGh? NIPjNmlFVVOR M{LWXWlEPTB;MD65OUDPxE1? MnTOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
Sf9 NEC3XXJMcW6jc3WgRZN{[Xl? M3niclMxKG2rbh?= M2L1dGROW09? NULjeoVYUW6qaXLpeIlwdiCxZjDoeY1idiCSSUPL[4FudWFiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJIFud3WwdDDv[kBCXFBiY3;ud5Vu\WRid3n0bEBKSzVyIH;mJFAvODR{IN88US=> NXLkOoFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK1OFg{PDJpPkKyOVQ5OzR{PD;hQi=>
RAW 264.7 MVvLbY5ie2ViQYPzZZk> NEDDVGQ6OCCvaX6= NV7Fb4p5TE2VTx?= NWLTZoV3UW6qaXLpeIlwdiCxZjDoeY1idiCSSUPL[4FudWFiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQVvUJJBpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5{OUig{txO MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2OEO0Nkc,OjJ3NEizOFI9N2F-
Sf9 NITSZlZMcW6jc3WgRZN{[Xl? MXixJIg> MkTyTY5pcWKrdHnvckBw\iCJU2St[pV{\WRiaIXtZY4hemWlb33ibY5idnRiUFmzT4JmfGFiZYjwdoV{e2WmIHnuJIJi[3Wub4\pdpV{KGmwZnXjeIVlKFOIOTDj[YxteyC5aYToJGlEPTBib3[gNE4xOTdizszN NWXGUZJoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFA3PDVpPkKzOVQxPjR3PD;hQi=>
Sf9 MWPLbY5ie2ViQYPzZZk> NW\aNolIOSCq M2H0cmlvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2tl\Wy2YTDlfJBz\XO|ZXS= NIHSXZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W0NFY1PSd-MkO1OFA3PDV:L3G+
Sf9 MWDLbY5ie2ViQYPzZZk> NX3uOopOOSCq M37VU2lvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2to[W2vYTDlfJBz\XO|ZXS= MmThQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFUoRjJ|NUSwOlQ2RC:jPh?=
Sf9 MlXxT4lv[XOnIFHzd4F6 MoXINUBp M1fqVWlvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2tidHCqYTDlfJBz\XO|ZXS= M4fM[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUSwOlQ2Lz5{M{W0NFY1PTxxYU6=
SKOV3 MkDET4lv[XOnIFHzd4F6 NEPXXlMyKM7:TR?= NEjGeXQyKGh? NIP4R4dFVVOR MUXJcohq[mm2aX;uJI9nKFCLM1vhcJBp[SCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEGtdDDT[ZI1PzNicHjvd5Bpd3K7bHH0bY9v Mn;RQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN|NkCzOFgoRjJ|M{[wN|Q5RC:jPh?=
MCF7 NGSwc2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF[5T3IyKM7:TR?= MkDTPVYhcA>? MVTEUXNQ MkjhS2k2OD1yLkC3NFIh|ryP NEHkNWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O2NFM1QCd-MkOzOlA{PDh:L3G+
SKOV3 MoTiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYe0fmtMOSEQvF2= M2PTW|k3KGh? NH7SV5VFVVOR MYnHTVUxRTBwMUS3OkDPxE1? NG\lXm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O2NFM1QCd-MkOzOlA{PDh:L3G+
PC3 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTscWRHPzJiaB?= NX\TXllETE2VTx?= M1HxfGlEPTB;MD6yPEDPxE1? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6MUexOEc,OjF7OEG3NVQ9N2F-
MCF7.1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTrO|IhcA>? M{jMOmROW09? NXzsdmdiSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NjFiY3XscJMh\XiycnXzd4lv\yCKRWKyJIdmdmVid3n0bEBKSzVyIH;mJFAvOjhizszN NW\TcJBMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5PFE4OTRpPkKxPVgyPzF2PD;hQi=>
MCF7-neo/Her2 M2nSSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzTUmFUPzJiaB?= M4f0b2ROW09? MlHNTWM2OD1yLkK5JO69VQ>? MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ4MkmwN{c,OjN4NkK5NFM9N2F-
MCF7-neo/Her2 MonlT4lv[XOnIFHzd4F6 MXfJcohq[mm2aX;uJI9nKFCLM1vhcJBp[SCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhSUuWIIDoc5NxcG:{eXzheIlwdiCjdDDTOFc{KHerdHigTWM2OCCxZjCwMlAxPyEQvF2= NIjZTJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[2NlkxOyd-MkO2OlI6ODN:L3G+
PC3 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmLyO|IhcA>? MUjEUXNQ NHjDT|RGSzVyPUCuN|Qh|ryP MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6NU[zPUc,OjF7OEW2N|k9N2F-
MCF7.1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV3jXnJrPzJiaB?= MmfzSG1UVw>? NXHBZ5pNSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NjFiY3XscJMh\XiycnXzd4lv\yCSSUPLZYxxcGFibYX0ZY51KHerdHigSWM2OCCxZjCwMlM6KM7:TR?= MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl6NU[zPUc,OjF7OEW2N|k9N2F-
PC3 NGjxcFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWi3NkBp NU\6bFJYTE2VTx?= Mnu3RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNiZHXmbYNq\W62IHnuJHBVTU5id3n0bEBKSzVyIH;mJFAvOzlizszN MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODB3ME[2PUc,OjByNUC2Olk9N2F-
MCF7.1 MlnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYnyb4hKPzJiaB?= MXjEUXNQ NGXaPGpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSlcvOSClZXzsd{BmgHC{ZYPzbY5oKFCLM1vhcJBp[SCvdYThcpQhf2m2aDDJR|UxKG:oIECuN|Qh|ryP M{nUOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMEWwOlY6Lz5{MEC1NFY3QTxxYU6=
MCF7.1 M2ntb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHjSmY4OiCq M2HrW2VEPTB;MD63NkDPxE1? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODN2Nk[1Okc,OjB|NE[2OVY9N2F-
NCI-H1975 M3TxbWN6fG:2b4jpZ{BCe3OjeR?= MWi3NkBp MUDJR|UxRTBwMkeg{txO NEjXT4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
H460 MmDWR5l1d3SxeHnjJGF{e2G7 NF3EUHc4OiCq M37jSmlEPTB;MD64O{DPxE1? NInVVFI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
HT-29 MmjMR5l1d3SxeHnjJGF{e2G7 MXu3NkBp MXjJR|UxRTBwNk[g{txO M3HoVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
HepG2 M3z5TWN6fG:2b4jpZ{BCe3OjeR?= NFXES3A4OiCq NYTyTHBQUUN3ME2xJO69VQ>? NITNTY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
SGC7901 Mn7RR5l1d3SxeHnjJGF{e2G7 MkXJO|IhcA>? Ml6zTWM2OD1zLkig{txO M4LTTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
NCI-H226 MmfFR5l1d3SxeHnjJGF{e2G7 NITOTFE4OiCq NV3GeY5UUUN3ME2yMlkh|ryP M3H3OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
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Assay
Methods Test Index PMID
Western blot p-AKT / AKT / p-FoxO3a / FoxO3a / PUMA ; p-S6RP / S6RP ; p-4EBP1 / 4EBP1 ; p-LRP6 / LRP6 ; p-PAK / PAK1 / p-CRAF / RAF / p-MEK / MEK / p-ERK / ERK 29137323 30042442 25857298 24327733
Immunofluorescence p65 ; beta-catenin 30042442 25857298
Growth inhibition assay Cell viability 27117832
In vivo GDC-0941 shows limited microsomal metabolism, resulting in 78% oral bioavailability [5]. Administration of GDC-0941 at 75 mg/kg/day displays significant inhibitory effect against established human U87MG glioblastoma xenografts in female NCr athymic mice, with tumor growth inhibition of 83%. [1] Oral administration of GDC-0941 at 150 mg/kg/day inhibits the growth of HER2-amplified, trastuzumab-resistant MDA-MB-361.1 xenografts in mice, and significantly delays the tumor progression, in association with potent induced apoptosis in tumors. [2] GDC-0941 (75 mg/kg/day) treatment for 2 weeks induces ~40% reduction in tumor volume of spontaneous B-cell follicular lymphomas developed in PTEN+/-LKB1+/hypo mice, accompanied by ablation of phosphorylation of Akt, S6K and SGK (serum and glucocorticoid protein kinase) protein kinases. [4]

Protocol (from reference)

Kinase Assay:

[1]

  • Scintillation proximity assay:

    Recombinant human PI3Kα, PI3Kβ, and PI3Kδ are coexpressed in a Sf9 baculovirus system with the p85α regulatory subunit and purified as GST-fusion proteins using affinity chromatography on glutathione-sepharose. Recombinant human PI3Kγ is expressed as monomeric GST-fusions and purified similarly. GDC-0941 is dissolved in DMSO and added to 20 mM Tris-HCl (pH 7.5) containing 200 μg yttrium silicate (Ysi) polylysine SPA beads, 4 mM MgCl2, 1 mM dithiothreitol (DTT), 1 μM ATP, 0.125 μCi [γ-33P]-ATP, and 4% (v/v) DMSO in a total volume of 50 μL. The recombinant GST-fusion of PI3Kα (5 ng), PI3Kβ (5 ng), PI3Kδ (5 ng), or PI3Kγ (5 ng) is added to the assay mixture to initiate the kinase reaction. After incubation for 1 hour at room temperature, the kinase reaction is terminated with 150 μL PBS. The mixture is then centrifuged for 2 minutes at 2000 rpm and read using a Wallac Microbeta counter. The reported IC50 values are calculated using a sigmoidal, dose-response curve fit in MDL Assay Explorer.

Cell Research:

[2]

  • 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, and MKN-7 cells
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 48 and 72 hours
  • Method:

    Cells are exposed to various concentrations of GDC-0941 for 48, and 72 hours. Proliferation/viability of cells is detected by using the CellTiter-Glo Luminescent Cell Viability Assay. The pAkt (Ser473), cleaved caspase-3, and cleaved PARP are analyzed by western blot. The Caspase-Glo 3/7 assay and the Cell Death Detection ELISAplus assay are used to detect caspase 3/7 activity, and apoptosis, respectively.

Animal Research:

[2]

  • Animal Models: NCR nude mice implanted with MDA-MB-361.1 cells, and SCID, C.B-17/IcrHsd-Prkdcscid mice implanted subcutaneously with BT474-M1 cells
  • Dosages: ~150 mg/kg/day
  • Administration: Oral gavage

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 513.64
Formula

C23H27N7O3S2

CAS No. 957054-30-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02092831 Completed Drug: GDC-0941 Healthy Volunteer Genentech Inc. April 2014 Phase 1
NCT01740336 Completed Drug: GDC-0941|Drug: Placebo|Drug: Paclitaxel Breast Cancer Genentech Inc. February 6 2013 Phase 2
NCT01474668 Completed Drug: GDC-0941 Healthy Volunteer Genentech Inc. October 2011 Phase 1
NCT01240226 Completed Drug: GDC-0941|Drug: ketoconazole Healthy Volunteer Genentech Inc. November 2010 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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