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 367 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 NXfaOoxFU2mwYYPlJGF{e2G7 MV[xJIg> NVLNNXdMTE2VTx?= NXLGNWtCUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDQTVNMKHBzMUDk[Yx1[SCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJINw\XiycnXzd4lv\yCyOEXhcJBp[SC5aYToJGlEPTBib3[gNE4xODNizszN NWDYcJN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
Sf9 MXrLbY5ie2ViQYPzZZk> MXyxJIg> MmfaSG1UVw>? NXjoRZZzUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDQTVNMKHBzMUDi[ZRiKEhzMES3MXIhdXW2YX70JIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiY3;lfJBz\XO|aX7nJJA5PWGucHjhJJdqfGhiSVO1NEBw\iByLkCwN{DPxE1? NXn6UI4xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OVQ3PTRpPkG4O|U1PjV2PD;hQi=>
Sf9 MXnLbY5ie2ViQYPzZZk> NEPnOosyKGh? MUTEUXNQ MX\Jcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KFCLM1ugdFEyOGKndHGgSVU1PS2NIH31eIFvfCCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJINw\XiycnXzd4lv\yCyOEXhcJBp[SC5aYToJGlEPTBib3[gNE4xODNizszN M3jCUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
Sf9 MkLYT4lv[XOnIFHzd4F6 Mn;pNUBp NUTVTZZxTE2VTx?= Mn\FTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCSSUPLJJAyOTCkZYThJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiY3;lfJBz\XO|aX7nJJA5PWGucHjhJJdqfGhiSVO1NEBw\iByLkCzN{DPxE1? MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDd3NE[1OEc,OTh5NUS2OVQ9N2F-
Sf9 MkW4T4lv[XOnIFHzd4F6 NXnwZWtHOSCq NXXLSIpSTE2VTx?= MULJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KFCLM1ugdFEyOGGucHjhJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiY3;lfJBz\XO|aX7nJJA5PWGucHjh MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDd3NE[1OEc,OTh5NUS2OVQ9N2F-
MDA-MB-361 M4fvXWZ2dmO2aX;uJGF{e2G7 MkjPNkBp NHntOXVFVVOR MYTJcohq[mm2aX;uJI9nKEGtdDDT[ZI1PzNicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKE2GQT3NRk0{PjFiY3XscJMhf2m2aDDQTWs{S0FiRUW0OU1MKG23dHH0bY9vKHerdHigTWM2OCCxZjCwMlAzQCEQvF2= M{TMc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
PC3 MnTXSpVv[3Srb36gRZN{[Xl? NXPp[HpIOiCq NEm1OWFFVVOR NIT4ZZhKdmirYnn0bY9vKG:oIFHreEBU\XJ2N{OgdIhwe3Cqb4L5cIF1cW:wIHnuJHBVTU5vboXscEBpfW2jbjDQR|Mh[2WubIOge4l1cCCLQ{WwJI9nKDBwMEO3JO69VQ>? M3jRZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
U87MG M4rtVWZ2dmO2aX;uJGF{e2G7 Mnj1NkBp MYPEUXNQ NUfQV2QyUW6qaXLpeIlwdiCxZjDBb5QhW2W{NEezJJBpd3OyaH;yfYxifGmxbjDpckBRXEWQLX71cIwhcHWvYX6gWVg4VUdiY3XscJMhf2m2aDDJR|UxKG:oIECuNFQ3KM7:TR?= M1m2[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
MDA-MB-361 NVPQbJZGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHyycIE6PiCq MXTEUXNQ NFW3cFFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3ERU1OSi1|NkGgZ4VtdHNid3n0bEBRUUt|Q1GgSVU1PS2NIH31eIF1cW:wIIfpeIghUUN3MDDv[kAxNjd{IN88US=> M3W0SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
A2780 NV\o[pE1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnBWmR5QTZiaB?= NWLte2Y3TE2VTx?= M1TCcWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUK3PFAh[2WubIOge4l1cCCSSVuzR2Eh[W6mIGDUSW4hdXW2YYTpc44hf2m2aDDJR|UxKG:oIECuNVQh|ryP M2Xzc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6N{W0OlU1Lz5zOEe1OFY2PDxxYU6=
PC3 MlroS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NET5cok6PiCq MnLpSG1UVw>? NIn6TY5KSzVyPUCuNlgh|ryP MorkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5NUS2OVQoRjF6N{W0OlU1RC:jPh?=
U87MG MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fnZ|k3KGh? NF\CNmtFVVOR MWDJR|UxRTBwOUWg{txO MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDd3NE[1OEc,OTh5NUS2OVQ9N2F-
Sf9 NX60c2JPU2mwYYPlJGF{e2G7 MnO4N|AhdWmw NUjWSY52TE2VTx?= MkjwTY5pcWKrdHnvckBw\iCqdX3hckBRUTONZ3HtcYEh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IHHtc5VvfCCxZjDBWHAh[2:wc4Xt[YQhf2m2aDDJR|UxKG:oIECuNFQzKM7:TR?= M37BO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NUS4N|QzLz5{MkW0PFM1OjxxYU6=
RAW 264.7 MVjLbY5ie2ViQYPzZZk> MUW5NEBucW5? NIO3VGZFVVOR MYDJcohq[mm2aX;uJI9nKGi3bXHuJHBKO0upYX3tZUBmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBCU1RicHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCwMlI6QCEQvF2= MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2OEO0Nkc,OjJ3NEizOFI9N2F-
Sf9 NXvHNJRpU2mwYYPlJGF{e2G7 NWqxc|dpOSCq MXfJcohq[mm2aX;uJI9nKEeVVD3meZNm\CCqdX3hckBz\WOxbXLpcoFvfCCSSUPLZoV1[SCneIDy[ZN{\WRiaX6gZoFkfWyxdnnyeZMhcW6oZXP0[YQhW0Z7IHPlcIx{KHerdHigTWM2OCCxZjCwMlAyPyEQvF2= MoPKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFUoRjJ|NUSwOlQ2RC:jPh?=
Sf9 MWLLbY5ie2ViQYPzZZk> M4jEUFEhcA>? M4T2UWlvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2tl\Wy2YTDlfJBz\XO|ZXS= M1T2O|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUSwOlQ2Lz5{M{W0NFY1PTxxYU6=
Sf9 M4Lhd2tqdmG|ZTDBd5NigQ>? NI\3T|cyKGh? M2fXUGlvcGmkaYTpc44hd2ZiR2PUMYZ2e2WmIHj1cYFvKHKnY3;tZolv[W62IGDJN2to[W2vYTDlfJBz\XO|ZXS= M1TRTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUSwOlQ2Lz5{M{W0NFY1PTxxYU6=
Sf9 MljoT4lv[XOnIFHzd4F6 NVOyOpBLOSCq Mn;UTY5pcWKrdHnvckBw\iCJU2St[pV{\WRiaIXtZY4hemWlb33ibY5idnRiUFmzT4FteGijIHX4dJJme3OnZB?= Mn3CQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFUoRjJ|NUSwOlQ2RC:jPh?=
SKOV3 M3PMc2tqdmG|ZTDBd5NigQ>? M2DBRlEh|ryP NH7CU4EyKGh? M{HVbmROW09? MYPJcohq[mm2aX;uJI9nKFCLM1vhcJBp[SCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEGtdDDT[ZI1PzNicHjvd5Bpd3K7bHH0bY9v MkLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN|NkCzOFgoRjJ|M{[wN|Q5RC:jPh?=
MCF7 MlHvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnBNIIyKM7:TR?= MWG5OkBp NVHFO2ZRTE2VTx?= MVnHTVUxRTBwMEewNkDPxE1? NH7pXFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O2NFM1QCd-MkOzOlA{PDh:L3G+
SKOV3 M1LtVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkDTNUDPxE1? MYG5OkBp M{fOUGROW09? MVPHTVUxRTBwMUS3OkDPxE1? MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN4MEO0PEc,OjN|NkCzOFg9N2F-
PC3 MmnrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrNU2xVPzJiaB?= NFru[YxFVVOR NXfQdIVXUUN3ME2wMlI5KM7:TR?= MonvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEG3NVQoRjJzOUixO|E1RC:jPh?=
MCF7.1 NIXFS|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV[3NkBp NGXIWZNFVVOR MX7BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRkeuNUBk\WyuczDlfJBz\XO|aX7nJGhGWjJiZ3Xu[UB4cXSqIFnDOVAhd2ZiMD6yPEDPxE1? MmHTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEG3NVQoRjJzOUixO|E1RC:jPh?=
MCF7-neo/Her2 Mn71S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV7ZVFQ6PzJiaB?= NF;XU4NFVVOR M161ZWlEPTB;MD6yPUDPxE1? M1vXZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|Nk[yPVA{Lz5{M{[2NlkxOzxxYU6=
MCF7-neo/Her2 NID6bFdMcW6jc3WgRZN{[Xl? MXnJcohq[mm2aX;uJI9nKFCLM1vhcJBp[SCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhSUuWIIDoc5NxcG:{eXzheIlwdiCjdDDTOFc{KHerdHigTWM2OCCxZjCwMlAxPyEQvF2= NXHTeHh6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OlI6ODNpPkKzOlYzQTB|PD;hQi=>
PC3 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXjKTFBHPzJiaB?= NFP1SJRFVVOR NGD0V5pGSzVyPUCuN|Qh|ryP M2\abVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUi1OlM6Lz5{MUm4OVY{QTxxYU6=
MCF7.1 M1PxUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHO4VWY4OiCq M17HNWROW09? NVvOPGpFSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4NjFiY3XscJMh\XiycnXzd4lv\yCSSUPLZYxxcGFibYX0ZY51KHerdHigSWM2OCCxZjCwMlM6KM7:TR?= MnXoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7OEW2N|koRjJzOUi1OlM6RC:jPh?=
PC3 NWnrU29nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV[3NkBp NX;0RVRTTE2VTx?= MnfqRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNiZHXmbYNq\W62IHnuJHBVTU5id3n0bEBKSzVyIH;mJFAvOzlizszN M1\wXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMEWwOlY6Lz5{MEC1NFY3QTxxYU6=
MCF7.1 M3jMSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofwO|IhcA>? MX\EUXNQ MXfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRkeuNUBk\WyuczDlfJBz\XO|aX7nJHBKO0ujbIDoZUBufXSjboSge4l1cCCLQ{WwJI9nKDBwM{Sg{txO MorGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByNUC2OlkoRjJyMEWwOlY6RC:jPh?=
MCF7.1 MkPIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3vzSlczKGh? MnvoSWM2OD1yLkeyJO69VQ>? M{jXd|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyM{S2OlU3Lz5{MEO0OlY2PjxxYU6=
NCI-H1975 NGnwZYZEgXSxdH;4bYMhSXO|YYm= MnXUO|IhcA>? MoDJTWM2OD1yLkK3JO69VQ>? M{HXVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
H460 NWHNVolRS3m2b4TvfIlkKEG|c3H5 NEjzOWk4OiCq NYDyb5FlUUN3ME2wMlg4KM7:TR?= M1\XSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
HT-29 Mk\PR5l1d3SxeHnjJGF{e2G7 MXy3NkBp NEnUeXNKSzVyPUCuOlYh|ryP MkXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNUm1OFUoRjJ|MEW5OVQ2RC:jPh?=
HepG2 MkDZR5l1d3SxeHnjJGF{e2G7 NGX3[Io4OiCq NFzyW3BKSzVyPUGg{txO M2nxWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW5OVQ2Lz5{M{C1PVU1PTxxYU6=
SGC7901 MUXDfZRwfG:6aXOgRZN{[Xl? NE[5OJE4OiCq MmLmTWM2OD1zLkig{txO NIfpRos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1PVU1PSd-MkOwOVk2PDV:L3G+
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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.

  • (Only for Reference)
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
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 44 mg/mL
(85.66 mM)
Water Insoluble
Ethanol Insoluble

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

* 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 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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