PI-103

Catalog No.S1038

For research use only.

PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. PI-103 induces apoptosis in murine T-cell Lymphoma.

PI-103 Chemical Structure

CAS No. 371935-74-9

Selleck's PI-103 has been cited by 89 publications

Purity & Quality Control

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Biological Activity

Description PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. PI-103 induces apoptosis in murine T-cell Lymphoma.
Features The first potent, synthetic mTOR inhibitor.
Targets
p110α [3]
(Cell-free assay)
p110β [3]
(Cell-free assay)
p110δ [3]
(Cell-free assay)
p110γ [3]
(Cell-free assay)
DNA-PK [3]
(Cell-free assay)
Click to View More Targets
2 nM 3 nM 3 nM 15 nM 23 nM
In vitro

PI-103 potently inhibits both the rapamycin-sensitive (mTORC1) and rapamycin-insensitive (mTORC2) complexes of the protein kinase mTOR. [1] PI-103 inhibits constitutive and growth factor-induced PI3K/Akt, as well as mTORC1 activation. [2] In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis, especially in the compartment containing leukemic stem cells. PI-103 inhibits p110α >200-fold more potently than p110β. PI-103 also potently blocks production of PI(3,4)P2 and PIP3 in adipocytes and PIP3 in myotubes. [2] PI-103 inhibits phosphorylation of Akt with an IC95 100-fold lower than that for LY294002. Strikingly, PI-103 completely protects animals from insulin-stimulated decline in blood glucose. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
UCH-1  MmLERZBweHSxc3nzJGF{e2G7 NWPWS2VkOC5zLUGwJO69VQ>? M2XhNlI1KGh? MnLpSG1UVw>? NETIe5FqdmS3Y3XzJIFxd3C2b4Ppdy=> NGTlOmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWyPFQ1OSd-MUm1Nlg1PDF:L3G+
UCH-1  M2HaN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMlAyNTFyIN88US=> NYXyfHJKPiCm MWrpcohq[mm2czDwdo9tcW[ncnH0bY9vKGSxc3Wg[IVx\W6mZX70cJk> M4PFVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUK4OFQyLz5zOUWyPFQ1OTxxYU6=
UCH-1  NWHib5U5TnWwY4Tpc44hSXO|YYm= NUfjPGM3OC13IN88US=> NFu2RZhqdmirYnn0d{B1cGVicHjvd5Bpd3K7bHH0bY9vKG:oIHLveIghSUuWIHHu[EBuXE:UIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ Mo[0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl3Mki0OFEoRjF7NUK4OFQyRC:jPh?=
HUVEC NGH5[IZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2XEVWlEPTB;MD6wPEDPxE1? M3XLOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUi0NlI4Lz5zOUW4OFIzPzxxYU6=
SKOV-3 NXjWTolCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLQVG9KSzVyPUCuNVIh|ryP NUfHNmt7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm1PFQzOjdpPkG5OVg1OjJ5PD;hQi=>
PC3  NFrrb2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV3Ic3h2UUN3ME2wMlExKM7:TR?= NIj4fYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUW4OFIzPyd-MUm1PFQzOjd:L3G+
DETROIT562 NYOyO2hWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3jaeWlEPTB;MD6xN{DPxE1? M2XUSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUi0NlI4Lz5zOUW4OFIzPzxxYU6=
IGROV-1 NYnLTI5PT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTBwME[g{txO MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTV6NEKyO{c,OTl3OESyNlc9N2F-
U87MG M2j6Omdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTmTWM2OD1yLkG0JO69VQ>? NHTRSm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUW4OFIzPyd-MUm1PFQzOjd:L3G+
U118MG MYPGeY5kfGmxbjDBd5NigQ>? NHjJNXExNjFvMTFOwG0> Mmn6NlTjiImqwrC= NUO3TIVlTE2VTx?= M4DLT4lvcGmkaYTzJHBKO0tvbXXkbYF1\WRic3nncoFtcW6p M3frdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NkOzOlg{Lz5zOU[zN|Y5OzxxYU6=
U138MG MWPGeY5kfGmxbjDBd5NigQ>? MUiwMlEuOSEQvF2= MXyyOQKBkWkEoB?= NXuz[XZ6TE2VTx?= NIXBOJlqdmirYnn0d{BRUTONLX3l[IlifGWmIIPp[45idGmwZx?= M2nzOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NkOzOlg{Lz5zOU[zN|Y5OzxxYU6=
U87MG M4PNXGZ2dmO2aX;uJGF{e2G7 MXSwMlEuOSEQvF2= NGL2VVEzPOLCiXlCpC=> NFewbGZFVVOR M2rWbIlvcGmkaYTzJHBKO0tvbXXkbYF1\WRic3nncoFtcW6p MkP2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl4M{O2PFMoRjF7NkOzOlg{RC:jPh?=
PC3  NGf5c3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4fT[lI1cA>? NF[1UVRIUTVywrC9JFExOCCwTR?= Mn32QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB3NUGwOlEoRjJyNUWxNFYyRC:jPh?=
518A2 M4PZdmZ2dmO2aX;uJGF{e2G7 NHq4OXUxNjByMfMAl|HjiIoQvF2= MnL2NlQhcA>? NGDqbml{fXCycnXzd4V{KHCqb4PwbI9zgWyjdHnvckBw\iCyaH;zdIhifGmmeXygbY5we2m2b3ygN{1scW6jc3Wg[I94dnO2cnXhcUB1[XKpZYTz M17mR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMES4O|g2Lz5{MUC0PFc5PTxxYU6=
Mel-Juso  M3exWWZ2dmO2aX;uJGF{e2G7 MYmwMlAxOeLCk{JihKnPxE1? M{mzPFI1KGh? MXHzeZBxemW|c3XzJJBpd3OyaH;yfYxifGmxbjDv[kBxcG:|cHjheIllgWxiaX7vd4l1d2xiMz3rbY5ie2ViZH;3cpN1emWjbTD0ZZJo\XS| NYDrdJRGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGwOFg4QDVpPkKxNFQ5Pzh3PD;hQi=>
518A2  M3HQVGNmdGxiVnnhZoltcXS7IFHzd4F6 NGKzfVUxNjBz4pETNVDjiIoQvF2= MWe3NkBp M1\xS4lvcGmkaYTzJINmdGxidnnhZoltcXS7IHTvd4Uh\GWyZX7k[Y51dHl? MojzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFyNEi3PFUoRjJzMES4O|g2RC:jPh?=
Mel-Juso NWLD[VY6S2WubDDWbYFjcWyrdImgRZN{[Xl? NYjiW4lnOC5yMfMAl|Ex6oDLzszN M1GzVVczKGh? MWHpcohq[mm2czDj[YxtKH[rYXLpcIl1gSCmb4PlJIRmeGWwZHXueIx6 MlPCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFyNEi3PFUoRjJzMES4O|g2RC:jPh?=
SF767 NX31WI1JTnWwY4Tpc44hSXO|YYm= NFjtXZYyKM7:TR?= MmO4OFghcA>? NFXaTJJqdmS3Y3XzJIF2fG:yaHHnc5NwdWViZn;ycYF1cW:w M2KxWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzME[yPVk{Lz5{MUC2Nlk6OzxxYU6=
U373 MYTGeY5kfGmxbjDBd5NigQ>? NGDuO2IyKM7:TR?= MUW0PEBp NFvCWYpqdmS3Y3XzJIF2fG:yaHHnc5NwdWViZn;ycYF1cW:w MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB4Mkm5N{c,OjFyNkK5PVM9N2F-
U87 NH\Wc4VHfW6ldHnvckBCe3OjeR?= M3jOdVEh|ryP NIHp[HE1QCCq MmDJbY5lfWOnczDheZRweGijZ3;zc41mKG[xcn3heIlwdg>? MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB4Mkm5N{c,OjFyNkK5PVM9N2F-
LN229 NV3ZPIlmTnWwY4Tpc44hSXO|YYm= MUGxJO69VQ>? MlXpOFghcA>? MkfWbY5lfWOnczDheZRweGijZ3;zc41mKG[xcn3heIlwdg>? MkfzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFyNkK5PVMoRjJzME[yPVk{RC:jPh?=
PC-9  MnLRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLzWFMxNTNizszN MVW3NkBp M1jVU2lEPTB;MD64JO69VQ>? NVzN[W15RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGyNlA1PzRpPkKxNlIxPDd2PD;hQi=>
HCC827 MoPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\TU|AuOyEQvF2= M2S2NFczKGh? MYTJR|UxRTBwMzFOwG0> MkDvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF{MkC0O|QoRjJzMkKwOFc1RC:jPh?=
HCC1937 MnXRSpVv[3Srb36gRZN{[Xl? NV\iZYtkOSEQvF2= M4DQ[VI1KGh? NFHxPXhz\WS3Y3XzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiQVvU NX;PN4ZSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PFg2QTBpPkKyOFg5PTlyPD;hQi=>
SUM1315MO2 NHHpdFBHfW6ldHnvckBCe3OjeR?= MnWwNUDPxE1? NGPVT3ozPCCq NWDhTVVSemWmdXPld{B1cGVicHjvd5Bpd3K7bHH0bY9vKG:oIFHLWC=> NIPIOIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkS4PFU6OCd-MkK0PFg2QTB:L3G+
SUM149PT NETtRmFHfW6ldHnvckBCe3OjeR?= NEf3WYIyKM7:TR?= MYeyOEBp MXPy[YR2[2W|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSUuW MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR6OEW5NEc,OjJ2OEi1PVA9N2F-
MDA-MB-436 NF3ac5lHfW6ldHnvckBCe3OjeR?= M1foUFEh|ryP MnzFNlQhcA>? MYTy[YR2[2W|IITo[UBxcG:|cHjvdplt[XSrb36gc4YhSUuW MoL1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ2OEi1PVAoRjJ{NEi4OVkxRC:jPh?=
KMS12-BM  Mn24S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7mNE0zKM7:TR?= NF3UcXEzPCCq M4PMeWlEPTExvK6yJO69VQ>? NWTpUpI6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkzOzRpPkKyPFI6OjN2PD;hQi=>
NCI-H929 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXjLSmZ5OC1{IN88US=> MWCyOEBp NX\3ZpBoUUN3ME2wMlI2KM7:TR?= M1;VWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NlM1Lz5{MkiyPVI{PDxxYU6=
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LOUCY M{HuZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rHNFHjiIoQvF2= Ml\lO{Bl M{H5VYRm[3KnYYPld{B1cGViY3XscEBvfW2kZYKgd4lodmmoaXPhcpRtgQ>? NWO3XHNERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwN|gzPzNpPkKzNFM5Ojd|PD;hQi=>
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PF-382 NFPHXVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHr0UY4y6oDLzszN MonqO{Bl M4nWdIRm[3KnYYPld{B1cGViY3XscEBvfW2kZYKgd4lodmmoaXPhcpRtgQ>? MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB|OEK3N{c,OjNyM{iyO|M9N2F-
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Jurkat MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXizXGxqOeLCid88US=> MmO0O{Bl MnzM[IVkemWjc3XzJJRp\SClZXzsJI52dWKncjDzbYdvcW[rY3HueIx6 MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB|OEK3N{c,OjNyM{iyO|M9N2F-
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Assay
Methods Test Index PMID
Western blot p-AKT / AKT / p-S6K / S6K / p-S6 / S6 / p-p38 / p38 ; p-GSK3 / GSK3 / p-BAD / BAD / p-MDM2 / MDM2 / p-p27 / p27 ; β-TrCP1 / p-mTOR 18922908 25721419
Immunofluorescence autophagosomes / autolysosomes 26814436
Growth inhibition assay Cell viability 25721419
In vivo When tumors reach 50-100 mm3, animals are randomized and treated with vehicle or PI-103. PI-103 exhibits significant activity, decreasing average tumor size by 4-fold after 18 days. [2] Mice treated with PI-103 have no obvious signs of toxicity premorbidly (based on body weight, food and water intake, activity, and general exam) or at necropsy. Treated tumors display decreased levels of phosphorylated Akt and S6, consistent with blockade of p110α and mTOR. PI-103 treatment is cytostatic to glioma xenografts. [2]

Protocol (from reference)

Kinase Assay:[3]
  • Enzyme Assays:

    Phosphatidylinositide 3-kinase inhibitory activity was determined using a scintillation proximity assay in the presence of 1 μmol/L ATP. Inhibition of mTOR protein kinase was determined using a TR-FRET-based LanthaScreen method from Invitrogen. Compounds were assayed at a maximum concentration of 10 μmol/L in the presence of 1 μmol/L ATP, and IC50 values were determined using GraphPad Prism software.

Cell Research:[2]
  • Cell lines: U87MG cells
  • Concentrations: 0.5 μM
  • Incubation Time: 24 hours
  • Method: U87MG cells are treated with PI-103 for 24 hours. Cell death is quantified by colorimetric determination of LDH activity using a cytotoxicity detection kit. Percentage of cell death (mean of three 12-well plates per experimental point) is calculated [(experimental value- low control)/(high control -low control) × 100], where the low-control cells are DMSO treated and high-control cells are Triton treated (1% Triton X-100, 30 min, 37 °
Animal Research:[2]
  • Animal Models: 6- to 12-week-old Balbc nu/nu mice bearing U87MG:ΔEGFR cells
  • Dosages: 5 mg/kg
  • Administration: Administered via i.p.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O
For best results, use promptly after mixing.

1 mg/mL

Chemical Information

Molecular Weight 348.36
Formula

C19H16N4O3

CAS No. 371935-74-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O

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.

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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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