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 13 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 M3q3bGZ2dmO2aX;uJGF{e2G7 NFTubXoyODBibl2= M2TkbVMhcA>? M1O2XmROW09? MnexbY5pcWKrdIOgdnJPSSC|eX70bIV{cXN? MUGyOVY6OTF3OB?=
HUVECs  MmX2SpVv[3Srb36gRZN{[Xl? Mn3VOVAxdk1? M1LITFEhcA>? NEjKNItT\WS3Y3XzJGRVYC2Wcnnn[4Vz\WRiRX7kc5Rp\WyrYXygSJl{\nWwY4Tpc44> NHi5[nQzPTZ|NEWzPC=>
A549 MVPGeY5kfGmxbjDBd5NigQ>? M1HIb|AvOcLizszN MmnBNlQhcA>? MUTk[YNz\WG|ZYOgeIhmKHKnbHH0bZZmKFCNQz5OtUBt\X[nbDDvckBk\WyuIH3lcYJz[W6nIHPveJJm[XSnZDDBV{1KXg>? M1S4ZlI2OjF6MU[x
A549 MnztSpVv[3Srb36gRZN{[Xl? M{XKdFAvOcLizszN MXmyOEBp MXry[YR2[2W|IITo[UBmgHC{ZYPzbY9vKGyndnXsd{Bw\iCPTWCtNkwhVU2SLUmgZY5lKGmwdHXndolvKM7{MR?= MlLXNlUzOThzNkG=
A549 NXfjOmZvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVqwMlHDqM7:TR?= M3rMbFI1KGh? Mk\L[Y5p[W6lZYOg[5Jwf3SqIHnubIljcXSrb36gZ491emWjdHXkJJdqfGhiQWOtTXY> MWeyOVIyQDF4MR?=
Mel202 MkHvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV[wMlUh|ryP MkP5N{Bp NEL5XGRFVVOR M{PQbYVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 M3TPOVI1PTl3M{i1
92.1 NYLVb4pkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfRNE42KM7:TR?= NEDyc5A{KGh? MofYSG1UVw>? NIHHO|RmdmijbnPld{BKWi2rbnT1Z4VlKHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gQ>? NETQS2MzPDV7NUO4OS=>
OCM3 NF3qeotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TxSVAvPSEQvF2= M{TIW|MhcA>? MUjEUXNQ NWLkW3F4\W6qYX7j[ZMhUVJvaX7keYNm\CC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHl? MorSNlQ2QTV|OEW=
Mel202 NUfFd3N4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlm4NE42KM7:TR?= MlPkN{Bp NIPGdpdFVVOR M2XENIlv[3KnYYPld{BKWi2rbnT1Z4VlKGOnbHygZ5lkdGViYYLy[ZN1yqB? NFLCb4MzPDV7NUO4OS=>
92.1 NU[wVnJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX3wS|luOC53IN88US=> NIfMZ3E{KGh? M4\6T2ROW09? M4XWe4lv[3KnYYPld{BKWi2rbnT1Z4VlKGOnbHygZ5lkdGViYYLy[ZN1yqB? MkHNNlQ2QTV|OEW=
OCM3 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljWNE42KM7:TR?= NUPERmpDOyCq MUnEUXNQ NFzZcZZqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi NHfnco0zPDV7NUO4OS=>
Jeko-1 Mli5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTZNE01KM7:TR?= MXXEUXNQ NH3nUJNqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MXGyOFM3Ojl|NR?=
Mino NH;WOoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXPBTm5lOC12IN88US=> Ml7MSG1UVw>? NVvKUZN1cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? MlnwNlQ{PjJ7M{W=
Rec-1 NWPTSI1qT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmjBNE01KM7:TR?= M1\Re2ROW09? NEf1T4NqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 NF\TVFEzPDN4MkmzOS=>
SP49 NFi5dlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWOwMVQh|ryP MmfUSG1UVw>? NXnSNVk4cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? MYiyOFM3Ojl|NR?=
Jeko-1 MX3GeY5kfGmxbjDBd5NigQ>? NUSz[JU1Oi53IN88UeKh M{nVOVEzKGh? M2PUU2ROW09? MmXY[I94dnKnZ4XsZZRmeyCQRj5OvmIhfGG{Z3X0JIdmdmW| NGjId2czPDN4MkmzOS=>
Mino NXjlU|IzTnWwY4Tpc44hSXO|YYm= MUGyMlUh|ryPwrC= Ml;GNVIhcA>? NELONZhFVVOR MV\kc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN? MoTFNlQ{PjJ7M{W=
Rec-1 MlvsSpVv[3Srb36gRZN{[Xl? MkfENk42KM7:TdMg MYWxNkBp MorVSG1UVw>? M3PoVIRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= NHjnXJEzPDN4MkmzOS=>
SP49 NY\nPYhqTnWwY4Tpc44hSXO|YYm= NVW0cotPOi53IN88UeKh NVXuN24{OTJiaB?= M37jcGROW09? M17sfYRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= MlzoNlQ{PjJ7M{W=
CD3+ T  MXjGeY5kfGmxbjDBd5NigQ>? NET5dIgxNTVyMDDuUS=> MWOxJIg> Mom1bY5pcWKrdIOgUmYu|rqEIIDoc5NxcG:{eXzheIlwdiCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NWTTXYZROjN3N{OyPFM>
Mel202 NF3C[2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPYXlQxNTVizszN NGHlNI84OiCq MnPTSG1UVw>? MWLpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 MX2yNlY2Ozl4OB?=
Omm1.3 MkjHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXOwMVUh|ryP MlXNO|IhcA>? NI\reGRFVVOR NFrVNmRqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MXKyNlY2Ozl4OB?=
92.1 NHzDXmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXXlZpR6OC13IN88US=> M4DwWFczKGh? NHrw[5NFVVOR M1TUfIlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> MUiyNlY2Ozl4OB?=
Mel202 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV61JO69VQ>? M3njblI1KGh? NH;1V2pFVVOR NVfpbZJCcW6mdXPld{BIOSCjcoLld5TDqA>? MUeyNlY2Ozl4OB?=
Omm1.3 NWjBWJJrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\WSXQ2KM7:TR?= Mle2NlQhcA>? MYXEUXNQ NF\NVVBqdmS3Y3XzJGcyKGG{cnXzeOKh NGrqXWszOjZ3M{m2PC=>
92.1 M1XtbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVPkeXR6PSEQvF2= MV[yOEBp MYXEUXNQ M1vqfolv\HWlZYOgS|Eh[XK{ZYP0xsA> MVGyNlY2Ozl4OB?=
Mel202 NWfUfYxISXCxcITvd4l{KEG|c3H5 Ml3HOUDPxE1? MY[3NkBp NVvLS4g{TE2VTx?= NV7WV|RscW6mdXPld{BieG:ydH;zbZMhe2yrZ3j0cJk> M1vvc|IzPjV|OU[4
Omm1.3 MlPWRZBweHSxc3nzJGF{e2G7 M4nNdFUh|ryP M3z2ZlczKGh? Mn74SG1UVw>? M{SzRolv\HWlZYOgZZBweHSxc3nz NHHMS48zOjZ3M{m2PC=>
92.1 NIH5bJRCeG:ydH;zbZMhSXO|YYm= Mkj6OUDPxE1? NWjwbWZvPzJiaB?= M4q2TGROW09? M2rYcIlv\HWlZYOgZZBweHSxc3nzJJNq\26rZnPhcpRtgQ>? M1vzRlIzPjV|OU[4
Mel202 NIq5SmRHfW6ldHnvckBCe3OjeR?= M3PQb|Uh|ryP NYmzd4ZGOjRiaB?= NW\UOo5qcW6qaXLpeJMh\XiycnXzd4lwdiCjbnSgdIhwe3Cqb4L5cIF1cW:wIH;mJHBMSyCrc3;mc5Juew>? MXWyNlY2Ozl4OB?=
Omm1.3 MonCSpVv[3Srb36gRZN{[Xl? NXPaNmZjPSEQvF2= NEn3SHQzPCCq MYHpcohq[mm2czDlfJBz\XO|aX;uJIFv\CCyaH;zdIhwenmuYYTpc44hd2ZiUFvDJIl{d2[xcn3z M1;VcVIzPjV|OU[4
92.1 MXnGeY5kfGmxbjDBd5NigQ>? NWf3Zol6PSEQvF2= MnXFNlQhcA>? NYTkZo5ScW6qaXLpeJMh\XiycnXzd4lwdiCjbnSgdIhwe3Cqb4L5cIF1cW:wIH;mJHBMSyCrc3;mc5Juew>? Mk\mNlI3PTN7Nki=
HBL1 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2XVTFAvOTZvMkCg{txO MV61JIQ> M17Cc2lEPTB;MD61JO69VQ>? MVyyNVMzPDl{MB?=
TMD8 M3qwUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnoR|kxNjF4LUKwJO69VQ>? M171d|Uh\A>? MY\JR|UxRTBwMjFOwG0> MlTHNlE{OjR7MkC=
OCI-Ly10 NHqwNm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLoVFIxNjF4LUKwJO69VQ>? NX7rbXliPSCm NGH4cYtKSzVyPUGuN{DPxE1? M13zN|IyOzJ2OUKw
U2932 M{fab2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV[wMlE3NTJyIN88US=> M3W2VVUh\A>? M4DQcWlEPTB;MUCg{txO MUOyNVMzPDl{MB?=
OCI-Ly3 M1[0eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmGzNE4yPi1{MDFOwG0> NFjaUIo2KGR? NVXlSZJLUUN3MP-8olIxKM7:TR?= MWOyNVMzPDl{MB?=
SuDHL2 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTBVZJGOC5zNj2yNEDPxE1? M{DiU|Uh\A>? NEL4dpJKSzVy78{eNlAh|ryP MUCyNVMzPDl{MB?=
SuDHL4 NVvPbIkyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vXOFAvOTZvMkCg{txO MmfOOUBl MYLJR|Ux97zgMkCg{txO NUnwbo9WOjF|MkS5NlA>
DB MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLYNE4yPi1{MDFOwG0> MXu1JIQ> NV7kS4FzUUN3MP-8olIxKM7:TR?= MX6yNVMzPDl{MB?=
Jurkat IL-2 M4TxRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPPO3FKSzVyPU[uO|EhyrFiMz63OkDPxE1? NYX1RVVEOTl7NECyOVk>
PBMC IL-2 NYL6[4ZDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHtRo9tUUN3ME20Mlg1KMLzIEGuO|AhKM7:TR?= MnfGNVk6PDB{NUm=

... 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]
- Collapse
  • 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

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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