Sotrastaurin

Catalog No.S2791 Synonyms: AEB071

Sotrastaurin Chemical Structure

Molecular Weight(MW): 438.48

Sotrastaurin is a potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay; inactive to PKCζ. Phase 2.

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In DMSO USD 190 In stock
USD 170 In stock
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Cited by 12 Publications

4 Customer Reviews

  • Lysates from H3122 and MGH006 cells treated with 1 µM PMA in the presence or absence of 0.3 µM sotrastaurin (SOT) were fractionated. Immunoblotting was performed with the indicated antibodies.

    Cancer Cell, 2015, 27(3): 397-408 . Sotrastaurin purchased from Selleck.

    J-Lat A2 cells were stimulated by TPA (10 nM) for 24 h in the presence of the indicated concentrations of AUY922 and sotrastaurin, alone or in combination. Samples were analyzed by FACS and data plotted using MacSynergy II software. (A) Representative McSynergy II plot: areas of the graph above zero indicate an additive or synergistic effect. (B) Representative checkerboard grid used to calculate the plot shown in A.

    Proc Natl Acad Sci USA, 2014, 111(15): E1528-37. Sotrastaurin purchased from Selleck.

  • Primary mantle cell lymphoma (MCL) cells respond differentially to sotrastaurin and ibrutinib. Primary MCL cells (MCL01-MCL04) were treated with 3 μmol/l sotrastaurin or 400 nmol/l ibrutinib for 2 h (A) or 22 h (B) followed by a stimulation with 3 μg/ml anti-human IgM antibody for 10 min. Subsequently whole cell lysates were analysed by Western blotting. DMSO, dimethyl sulphoxide.

    Br J Haematol, 2016, 173(3):394-403. Sotrastaurin purchased from Selleck.

    Western blotting analysis of FLT3ePIM-1 signaling in MV4-11 cells treated with increasing concentrations of SGI-1776, quizartinib, or sotrastaurin for 24 h.

    Biochem Biophys Res Commun, 2018, 10.1016/j.bbrc.2018.07.049. Sotrastaurin purchased from Selleck.

Purity & Quality Control

Choose Selective PKC Inhibitors

Biological Activity

Description Sotrastaurin is a potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay; inactive to PKCζ. Phase 2.
Features Unlike former PKC inhibitors, Sotrastaurin does not enhance apoptosis of murine T-cell blasts in a model of activation-induced cell death.
Targets
PKCθ [1]
(Cell-free assay)
PKCβ1 [1]
(Cell-free assay)
PKCα [1]
(Cell-free assay)
PKCη [1]
(Cell-free assay)
PKCδ [1]
(Cell-free assay)
0.22 nM(Ki) 0.64 nM(Ki) 0.95 nM(Ki) 1.8 nM(Ki) 2.1 nM(Ki)
In vitro

Sotrastaurin (< 10μM) treatment effectively abrogated at low nanomolar concentration markers of early T-cell activation, such as interleukin-2 secretion and CD25 expression, in primary human and mouse T cells. Sotrastaurin (200 nM) inhibits the CD3/CD28 antibody- and alloantigen-induced T-cell proliferation responses in the absence of nonspecific antiproliferative effects. Sotrastaurin (<3 μM) markedly inhibits lymphocyte function-associated antigen-1-mediated T-cell adhesion. [1] Sotrastaurin(< 20 μM) selectively impair the proliferation of CD79 mutant ABC DLBCL cell lines, correlating with decreased NF-κB signaling avctivity. AEB071 at concentration of 5 μM induces G1 arrest and/or cell death in CD79 mutant cells. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
T cell M37Sd2Z2dmO2aX;uJGF{e2G7 NYm3RlZFOTByIH7N NWrHPWlNOyCq M4fDb2ROW09? M{nIcolvcGmkaYTzJJJTVkFic4nueIhme2m| M2nG[FI2PjlzMUW4
HUVECs  M3TrcWZ2dmO2aX;uJGF{e2G7 NGXBOFE2ODCwTR?= NYK5Xmh[OSCq NWTHSm9pWmWmdXPld{BFXFhvVILp[4dmemWmIFXu[I91cGWuaXHsJGR6e2[3bnP0bY9v NW\HZ3g{OjV4M{S1N|g>
A549 MYrGeY5kfGmxbjDBd5NigQ>? NWr2UWs6OC5zwrFOwG0> M2XOUlI1KGh? M1fQOoRm[3KnYYPld{B1cGVicnXsZZRqfmViUFvDMe6yKGyndnXsJI9vKGOnbHygcYVu[nKjbnWgZ491emWjdHXkJGFUNUmY NXXrZ|RvOjV{MUixOlE>
A549 M4PVZWZ2dmO2aX;uJGF{e2G7 MX:wMlHDqM7:TR?= MnLoNlQhcA>? NFrXS5pz\WS3Y3XzJJRp\SCneIDy[ZN{cW:wIHzleoVteyCxZjDNUXAuOixiTV3QMVkh[W6mIHnueIVoemmwIN8yNS=> M2T3e|I2OjF6MU[x
A549 NW\Td2tFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnIcYhpOC5zwrFOwG0> NFmwPY0zPCCq MkSy[Y5p[W6lZYOg[5Jwf3SqIHnubIljcXSrb36gZ491emWjdHXkJJdqfGhiQWOtTXY> NYLmfog2OjV{MUixOlE>
Mel202 NF7BVo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXOwMlUh|ryP MlHBN{Bp Mli5SG1UVw>? M2rE[IVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 NVWzfZY2OjR3OUWzPFU>
92.1 M1XGc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETUXnQxNjVizszN MkHKN{Bp M1;kbWROW09? M1q1OoVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 NGSxT4EzPDV7NUO4OS=>
OCM3 MkWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWSwMlUh|ryP M3vLOFMhcA>? MnjESG1UVw>? M1\TW4VvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 NYXlWFk{OjR3OUWzPFU>
Mel202 MnXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\ISHgxNjVizszN NF;DdJo{KGh? MmHzSG1UVw>? NH\nSmtqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi M1XL[VI1PTl3M{i1
92.1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXLkW4VzOC53IN88US=> NIXlbYM{KGh? NVvlN2pjTE2VTx?= NFnIVmdqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi MUeyOFU6PTN6NR?=
OCM3 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHu1VIsxNjVizszN MlW0N{Bp NX3SbGdyTE2VTx?= M4nHOYlv[3KnYYPld{BKWi2rbnT1Z4VlKGOnbHygZ5lkdGViYYLy[ZN1yqB? M1Oyd|I1PTl3M{i1
Jeko-1 MlmzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDQeIRpOC12IN88US=> NF\DPGFFVVOR NWrNc2U{cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? MkTsNlQ{PjJ7M{W=
Mino NYX0TXZPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnVNE01KM7:TR?= NHTlZpRFVVOR NY[4PW1PcW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NUns[Go6OjR|NkK5N|U>
Rec-1 NH\lfnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{HXVFAuPCEQvF2= NWrBeHBSTE2VTx?= MWrpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 MkfmNlQ{PjJ7M{W=
SP49 MmP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUOwMVQh|ryP MWDEUXNQ MkTqbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MlPCNlQ{PjJ7M{W=
Jeko-1 MVXGeY5kfGmxbjDBd5NigQ>? NVHTcnBIOi53IN88UeKh MVKxNkBp MlnwSG1UVw>? MkLW[I94dnKnZ4XsZZRmeyCQRj5OvmIhfGG{Z3X0JIdmdmW| NUTJXmdrOjR|NkK5N|U>
Mino NYXGOZNVTnWwY4Tpc44hSXO|YYm= MW[yMlUh|ryPwrC= NUPle3VYOTJiaB?= MYLEUXNQ MYrkc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN? MoXXNlQ{PjJ7M{W=
Rec-1 MofhSpVv[3Srb36gRZN{[Xl? MnX6Nk42KM7:TdMg M2rGflEzKGh? M{LWOGROW09? M3zFPIRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= MUSyOFM3Ojl|NR?=
SP49 NEP4SZNHfW6ldHnvckBCe3OjeR?= M{[wUFIvPSEQvF5CpC=> NFfy[WwyOiCq NHvXWlBFVVOR NX7kSpl3\G:5boLl[5Vt[XSnczDOSk3PwkJidHHy[4V1KGenbnXz NV7TbGFnOjR|NkK5N|U>
CD3+ T  Mni2SpVv[3Srb36gRZN{[Xl? NGPWd2QxNTVyMDDuUS=> M1zX[|EhcA>? MmSzbY5pcWKrdIOgUmYu|rqEIIDoc5NxcG:{eXzheIlwdiCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MmTKNlM2PzN{OEO=
Mel202 M2nON2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVnQenh3OC13IN88US=> Mmf2O|IhcA>? NUTJboNDTE2VTx?= NVHldGMzcW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? Ml7qNlI3PTN7Nki=
Omm1.3 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU[wMVUh|ryP M4HUbVczKGh? MWnEUXNQ MnjDbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NX\4WWlUOjJ4NUO5Olg>
92.1 Mny5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIDSWIkxNTVizszN MlTIO|IhcA>? MlTUSG1UVw>? MonDbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NEnLWIUzOjZ3M{m2PC=>
Mel202 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\OdlUh|ryP MoW5NlQhcA>? MnzMSG1UVw>? MlvNbY5lfWOnczDHNUBienKnc4VCpC=> NUH3OpZIOjJ4NUO5Olg>
Omm1.3 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1O4ZVUh|ryP M3XjZ|I1KGh? NGLidI1FVVOR NFnjNYlqdmS3Y3XzJGcyKGG{cnXzeOKh NYTKZoRpOjJ4NUO5Olg>
92.1 NGrvT2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILRNnQ2KM7:TR?= MVWyOEBp NHr1PHZFVVOR NXPzcm82cW6mdXPld{BIOSCjcoLld5TDqA>? M2HkPVIzPjV|OU[4
Mel202 M3nPVGFxd3C2b4Ppd{BCe3OjeR?= NXjBWlJ4PSEQvF2= NUnGV4xPPzJiaB?= NX\tR3ZOTE2VTx?= NV;KVXB1cW6mdXPld{BieG:ydH;zbZMhe2yrZ3j0cJk> MYiyNlY2Ozl4OB?=
Omm1.3 MWfBdI9xfG:|aYOgRZN{[Xl? MofoOUDPxE1? NVPhb|V7PzJiaB?= NVLzWVI6TE2VTx?= NIHVdoVqdmS3Y3XzJIFxd3C2b4Ppdy=> M3;wT|IzPjV|OU[4
92.1 NI\IfGJCeG:ydH;zbZMhSXO|YYm= NV3QPVJYPSEQvF2= M{XDblczKGh? NGfH[IFFVVOR NIH5SoVqdmS3Y3XzJIFxd3C2b4Ppd{B{cWewaX\jZY51dHl? MmHaNlI3PTN7Nki=
Mel202 MonISpVv[3Srb36gRZN{[Xl? NFLwWZg2KM7:TR?= MXOyOEBp MV3pcohq[mm2czDlfJBz\XO|aX;uJIFv\CCyaH;zdIhwenmuYYTpc44hd2ZiUFvDJIl{d2[xcn3z M3ywZlIzPjV|OU[4
Omm1.3 M133S2Z2dmO2aX;uJGF{e2G7 MXO1JO69VQ>? NYfrcJd2OjRiaB?= MXXpcohq[mm2czDlfJBz\XO|aX;uJIFv\CCyaH;zdIhwenmuYYTpc44hd2ZiUFvDJIl{d2[xcn3z Ml\nNlI3PTN7Nki=
92.1 NFvOZXdHfW6ldHnvckBCe3OjeR?= M{HWbVUh|ryP NUPzcm1POjRiaB?= M{faWIlvcGmkaYTzJIV5eHKnc4Ppc44h[W6mIIDoc5NxcG:{eXzheIlwdiCxZjDQT2MhcXOxZn;ycZM> NFzGPXUzOjZ3M{m2PC=>
HBL1 NWm3OW45T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUj1fHFLOC5zNj2yNEDPxE1? M{nVdFUh\A>? MV3JR|UxRTBwNTFOwG0> M1HCUlIyOzJ2OUKw
TMD8 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWnQZnRYOC5zNj2yNEDPxE1? MVy1JIQ> NIPnO4dKSzVyPUCuNkDPxE1? MYeyNVMzPDl{MB?=
OCI-Ly10 NWTBOpB6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYSwMlE3NTJyIN88US=> MnLzOUBl M3nQNGlEPTB;MT6zJO69VQ>? NU[4dnRyOjF|MkS5NlA>
U2932 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUGwMlE3NTJyIN88US=> M2DYTFUh\A>? MVXJR|UxRTFyIN88US=> M3zsSlIyOzJ2OUKw
OCI-Ly3 M17aSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{nmOFAvOTZvMkCg{txO MWC1JIQ> M1vYRmlEPTExvK6yNEDPxE1? MlXhNlE{OjR7MkC=
SuDHL2 MnK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLr[VkxNjF4LUKwJO69VQ>? NWnLblhCPSCm MkPXTWM2OO,:nkKwJO69VQ>? MXyyNVMzPDl{MB?=
SuDHL4 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH[0OYExNjF4LUKwJO69VQ>? NHP6cVM2KGR? MnfiTWM2OO,:nkKwJO69VQ>? NHnWclkzOTN{NEmyNC=>
DB Mn;YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUmwMlE3NTJyIN88US=> NHrLXo02KGR? M4q3V2lEPTExvK6yNEDPxE1? NV\SRWMyOjF|MkS5NlA>
Jurkat IL-2 NVrKTWdHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTZwN{GgxtEhOy55NjFOwG0> MnjaNVk6PDB{NUm=
PBMC IL-2 Mn\OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX2zSlFMUUN3ME20Mlg1KMLzIEGuO|AhKM7:TR?= M{HCNVE6QTRyMkW5

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pPKCδ/θ / phosphorylated MARCKS / p53 / MDM2 / PUMA / p21; 

PubMed: 29593251     


Cell lines OMM2.3, OMM2.5 and OMM1 were treated with 8 µM Nutlin-3 and 4 µM Sotrastaurin. MEL290 was incubated with 2 µM Nutlin-3 and 4 µM Sotrastaurin, cell line MM28 with 8 µM Nutlin-3 and 1 µM Sotrastaurin, and cell lines MEL202, MEL270 and MM66 with 2䲧疝Ỵ疞㧀疜膉痘 瘿�෋ᾰƌ෋à 㺣痖帉痖Ѐ瑖堘𢡄빢᎒෋à鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ뙠ෆ䐺痖暼瘿뙠ෆᾰƌ 뙠ෆÐ㺣痖뙠ෆ€𢡄뙤ෆ€䀷痗뙤ෆ౴뙤ෆ㵶痗뙤ෆ뺖᎒泌Itemセ᎒Count﫨呂뚔ෆ猴፲뙤ෆ፲씢痗猸፲髸莤䥷堙᎒セ᎒�堞ﻮ᎒፲露𢡄堚Ѽ齃礤v�堞ﻮ᎒猢Wセ᎒䨼Ą鹿齃

Cyclin D1 / p27(Kip1) ; 

PubMed: 22653968     


AEB071 selectively increased p27 and decreased cyclin D1 expression in GNAQ mutant UM cells. Cells were treated with 0, 2, or 5 μM AEB071 for 72 hours and analyzed by immunoblot. WT = GNAQ wild type; MT = GNAQ mutation.

Bcl-xl / XIAP / Survivin ; 

PubMed: 22653968     


AEB071 decreased the expression of antiapoptotic proteins Bcl-xL, XIAP, and survivin in GNAQ mutated cells. WT = GNAQ wild type; MT = GNAQ mutation.

PKCα / PKCδ / PKCβ / PKCε / PKCθ ; 

PubMed: 22653968     


AEB071 inhibited PKC expression in UM cells. Cells were treated with 5 μM AEB071 for 24 hours in the presence of 10% FBS and subjected to immunoblot analysis. PKCδ, ε and θ levels in AEB treated cells relative to control (DMSO treated) cells are also show䲧疝Ỵ疞㧀疜膉痘 瘿⟸෕ᾰƌ෕Ð 㺣痖帉痖Ѐ瑖堘𢡄빢᎒෕Ð鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ戤瘯Ɖ삨Ղ䐺痖暼瘿삨Ղᾰƌ 삨Ղà㺣痖삨Ղ€𢡄사Ղ€䀷痗사Ղ౴사Ղ㵶痗사Ղ뺖᎒泌Itemセ᎒Count﫨呂샜Ղ猴፲사Ղ፲씢痗猸፲髸莤䥷堙᎒

p-Marcks / p-ERK / p-AKT / p-S6 / Marcks / ERK / AKT / S6; 

PubMed: 22653968     


AEB071 inhibits PKC and mTOR pathways but not AKT. Western Blot of MARCKS, ERK, ribosomal S6 and AKT phosphorylation following drug treatments for 24 hrs. α-Tubulin was used as a loading control.

29593251 22653968
Growth inhibition assay
Cell viability ; 

PubMed: 22653968     


AEB071 selectively reduced viability of UM cells harboring GNAQ mutations. Cells were treated with varying amount of AEB071 for 72 hours. Data are presented as mean±SD of 4 or 5 independent experiments. NM = normal melanocytes; WT = GNAQ wild type; MT = G䲧疝Ỵ疞㧀疜膉

22653968
In vivo Sotrastaurin (80 mg/kg) results in significant inhibition of in vivo tumor growth in a subcutaneous TMD8 xenograft model in SCID. [2] Sotrastaurin orally administrated at 10 mg/kg and 30 mg/kg b.i.d. show a dose-dependent immunosuppressive effect leading to pronounced prolongation of heart allograft survival in rats. [3]

Protocol

Animal Research:[3]
+ Expand
  • Animal Models: male Wistar/F rats
  • Formulation: Saline
  • Dosages: 10 mg/kg and 30 mg/kg
  • Administration: Orally administrated
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 87 mg/mL (198.41 mM)
Ethanol 2 mg/mL (4.56 mM)
Water 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+ddH2O
For best results, use promptly after mixing.
10mg/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 438.48
Formula

C25H22N6O2

CAS No. 425637-18-9
Storage powder
in solvent
Synonyms AEB071

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02273219 Active not recruiting Drug: AEB071|Drug: BYL719 Uveal Melanoma Richard D. Carvajal|Columbia University November 2014 Phase 1
NCT01801358 Terminated Drug: AEB071|Drug: MEK162 Uveal Melanoma Array BioPharma August 2013 Phase 1|Phase 2
NCT01430416 Completed Drug: AEB071 Uveal Melanoma Novartis Pharmaceuticals|Novartis December 20 2011 Phase 1
NCT01402440 Terminated Drug: AEB071 Diffuse Large B-Cell Lymphoma Novartis Pharmaceuticals|Novartis November 2011 Phase 1

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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Frequently Asked Questions

  • Question 1:

    Could you give me the information about how to prepare Sotrastaurin for oral administration in mice?

  • Answer:

    S2791 Sotrastaurin can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution which can be used for injection, and in 2% DMSO/corn oil at 10 mg/ml as a suspension for oral administration.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID