Sotrastaurin

For research use only.

Catalog No.S2791 Synonyms: AEB071

32 publications

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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Selleck's Sotrastaurin has been cited by 32 publications

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 MWfGeY5kfGmxbjDBd5NigQ>? NFe3XogyODBibl2= NXHFWXZXOyCq NIXlN4dFVVOR NWT0blU1cW6qaXLpeJMhelKQQTDzfY51cGW|aYO= MmPxNlU3QTFzNUi=
HUVECs  NH3DVZFHfW6ldHnvckBCe3OjeR?= MnrwOVAxdk1? MUixJIg> MVjS[YR2[2W|IFTUXE1VemmpZ3Xy[YQhTW6mb4To[Yxq[WxiRInz[pVv[3Srb36= M4HFS|I2PjN2NUO4
A549 MXjGeY5kfGmxbjDBd5NigQ>? NFnFTlMxNjIEoN88US=> NGHYeG4zPCCq MV3k[YNz\WG|ZYOgeIhmKHKnbHH0bZZmKFCNQz5OtUBt\X[nbDDvckBk\WyuIH3lcYJz[W6nIHPveJJm[XSnZDDBV{1KXg>? NXv4V|U4OjV{MUixOlE>
A549 NEDhRpNHfW6ldHnvckBCe3OjeR?= M{HiNFAvOcLizszN MnTaNlQhcA>? MlvHdoVlfWOnczD0bIUh\XiycnXzd4lwdiCuZY\lcJMhd2ZiTV3QMVItKE2PUD25JIFv\CCrboTl[5JqdiEQskG= NHO1SXkzPTJzOEG2NS=>
A549 NUfJPYxiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYmwMlHDqM7:TR?= NUfjdGZMOjRiaB?= M1LXTYVvcGGwY3XzJIdzd3e2aDDpcohq[mm2aX;uJINwfHKnYYTl[EB4cXSqIFHTMWlX M4G4SlI2OjF6MU[x
Mel202 NVrjSFR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXuwMlUh|ryP NHLid5E{KGh? MVjEUXNQ M2r2OIVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 NEL3Xm4zPDV7NUO4OS=>
92.1 MlHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mom4NE42KM7:TR?= MXuzJIg> MYjEUXNQ NECzOFNmdmijbnPld{BKWi2rbnT1Z4VlKHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gQ>? MV:yOFU6PTN6NR?=
OCM3 MkDhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWSwMlUh|ryP Mom3N{Bp Ml7BSG1UVw>? MoPj[Y5p[W6lZYOgTXIucW6mdXPl[EBz\WS3Y4Tpc44hcW5iY3XscEB3cWGkaXzpeJk> M3LNcFI1PTl3M{i1
Mel202 MlLRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nmUFAvPSEQvF2= M4jGZ|MhcA>? NUPQenpsTE2VTx?= NGC4dllqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi NFvJWIwzPDV7NUO4OS=>
92.1 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnzONE42KM7:TR?= MkP6N{Bp M{nzNGROW09? MV\pcoNz\WG|ZYOgTXIucW6mdXPl[EBk\WyuIHP5Z4xmKGG{cnXzeOKh M2rEfFI1PTl3M{i1
OCM3 Mmm4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnwNE42KM7:TR?= NVXMeXRHOyCq MoLESG1UVw>? MlnwbY5kemWjc3XzJGlTNWmwZIXj[YQh[2WubDDjfYNt\SCjcoLld5TDqA>? NEW4fVEzPDV7NUO4OS=>
Jeko-1 M{[yb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHwNE01KM7:TR?= NV;weJMxTE2VTx?= M1Xwd4lvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> MUSyOFM3Ojl|NR?=
Mino MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnxZlExNTRizszN M1zmOmROW09? NIG3bZFqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MkTaNlQ{PjJ7M{W=
Rec-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYH0bFBnOC12IN88US=> MoPJSG1UVw>? M1jHfIlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> MnHhNlQ{PjJ7M{W=
SP49 M4PsdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXFbmcxNTRizszN MXTEUXNQ Mlz4bY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> M1O4O|I1OzZ{OUO1
Jeko-1 Mkj6SpVv[3Srb36gRZN{[Xl? Ml31Nk42KM7:TdMg M3;FOlEzKGh? NEHvNmVFVVOR M2joNoRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= MXyyOFM3Ojl|NR?=
Mino NXvLRYg3TnWwY4Tpc44hSXO|YYm= MYCyMlUh|ryPwrC= M2PhRlEzKGh? MnvDSG1UVw>? M3;Qb4Rwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= M2rIRVI1OzZ{OUO1
Rec-1 M2exUGZ2dmO2aX;uJGF{e2G7 NEXSWm4zNjVizszNxsA> M2PIZlEzKGh? NVzTO4k1TE2VTx?= NHXsRVJld3ewcnXneYxifGW|IF7GMe67SiC2YYLn[ZQh\2WwZYO= MmLENlQ{PjJ7M{W=
SP49 MUPGeY5kfGmxbjDBd5NigQ>? NFr2TWYzNjVizszNxsA> MoDQNVIhcA>? MYXEUXNQ M4PPboRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= Mn7jNlQ{PjJ7M{W=
CD3+ T  M3y5PGZ2dmO2aX;uJGF{e2G7 MkjJNE02ODBibl2= NX6wd|hyOSCq NVT1O2VNcW6qaXLpeJMhVkZvzsrCJJBpd3OyaH;yfYxifGmxbjDpckBiKGSxc3Wg[IVx\W6mZX70JI1idm6nch?= M3TVXVI{PTd|Mkiz
Mel202 NHrNTWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWGwMVUh|ryP MlT5O|IhcA>? M4\vOGROW09? NYryUmJOcW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NX2zWYJiOjJ4NUO5Olg>
Omm1.3 MlrkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXqwMVUh|ryP NHzFWY44OiCq MnPtSG1UVw>? NHrLWopqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MmjhNlI3PTN7Nki=
92.1 M{DMcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj6NE02KM7:TR?= NXmxPItlPzJiaB?= Mn;CSG1UVw>? MonKbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MY[yNlY2Ozl4OB?=
Mel202 NU\yWGdiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PUNFUh|ryP M4jFPVI1KGh? MkLxSG1UVw>? NXPnV5BMcW6mdXPld{BIOSCjcoLld5TDqA>? NVLaPY1IOjJ4NUO5Olg>
Omm1.3 NHvxSJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDDd2s5PSEQvF2= M1fQVVI1KGh? M2fkc2ROW09? MnfDbY5lfWOnczDHNUBienKnc4VCpC=> NYnH[ItLOjJ4NUO5Olg>
92.1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfwcZQ2KM7:TR?= Mnn6NlQhcA>? M{PPe2ROW09? NV3PUZBIcW6mdXPld{BIOSCjcoLld5TDqA>? M{\HZVIzPjV|OU[4
Mel202 NUXJRlVmSXCxcITvd4l{KEG|c3H5 M1vxZ|Uh|ryP MUe3NkBp NXTSV5JiTE2VTx?= M2f0U4lv\HWlZYOgZZBweHSxc3nzJJNtcWeqdHz5 MWeyNlY2Ozl4OB?=
Omm1.3 M{\XcmFxd3C2b4Ppd{BCe3OjeR?= M3e3cFUh|ryP MUC3NkBp Mn6wSG1UVw>? MVfpcoR2[2W|IHHwc5B1d3Orcx?= NU\zfYNYOjJ4NUO5Olg>
92.1 NX3xTHdWSXCxcITvd4l{KEG|c3H5 M4fHXFUh|ryP MUG3NkBp NVfW[WRnTE2VTx?= M{i2Solv\HWlZYOgZZBweHSxc3nzJJNq\26rZnPhcpRtgQ>? NWTGcppUOjJ4NUO5Olg>
Mel202 Ml\LSpVv[3Srb36gRZN{[Xl? NXjo[FZCPSEQvF2= NXrl[nBbOjRiaB?= NIH1b4xqdmirYnn0d{BmgHC{ZYPzbY9vKGGwZDDwbI9{eGixconsZZRqd25ib3[gVGtEKGm|b3\vdo1{ NH3ORZozOjZ3M{m2PC=>
Omm1.3 MWXGeY5kfGmxbjDBd5NigQ>? NUTEUoN7PSEQvF2= MVWyOEBp MkXybY5pcWKrdIOg[ZhxemW|c3nvckBidmRicHjvd5Bpd3K7bHH0bY9vKG:oIGDLR{Bqe2:ob4Ltdy=> M4HibFIzPjV|OU[4
92.1 MnjqSpVv[3Srb36gRZN{[Xl? MnXNOUDPxE1? MlHZNlQhcA>? MULpcohq[mm2czDlfJBz\XO|aX;uJIFv\CCyaH;zdIhwenmuYYTpc44hd2ZiUFvDJIl{d2[xcn3z MlTiNlI3PTN7Nki=
HBL1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWOwMlE3NTJyIN88US=> MoS5OUBl MoHTTWM2OD1yLkWg{txO NIXYd2UzOTN{NEmyNC=>
TMD8 NG\LR4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHe2SoIxNjF4LUKwJO69VQ>? M4HwO|Uh\A>? NV;1[4NSUUN3ME2wMlIh|ryP NVPOSG16OjF|MkS5NlA>
OCI-Ly10 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DDd|AvOTZvMkCg{txO MmPZOUBl MVnJR|UxRTFwMzFOwG0> NGixOXgzOTN{NEmyNC=>
U2932 M3rxNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmD0NE4yPi1{MDFOwG0> NWLtc2ZpPSCm NWjvcHJ3UUN3ME2xNEDPxE1? NFPBT5UzOTN{NEmyNC=>
OCI-Ly3 M2LaUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVmwMlE3NTJyIN88US=> MkfLOUBl NGXOO|lKSzVy78{eNlAh|ryP NELmSIQzOTN{NEmyNC=>
SuDHL2 NWLLRYNwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUW4ZmwyOC5zNj2yNEDPxE1? MXG1JIQ> M3rubmlEPTExvK6yNEDPxE1? MVKyNVMzPDl{MB?=
SuDHL4 M{n2Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWGwMlE3NTJyIN88US=> MYW1JIQ> M4XDWGlEPTExvK6yNEDPxE1? MY[yNVMzPDl{MB?=
DB M3HmZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUiwMlE3NTJyIN88US=> M2[wWFUh\A>? NF3oWpFKSzVy78{eNlAh|ryP M1e1XFIyOzJ2OUKw
Jurkat IL-2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYrJR|UxRTZwN{GgxtEhOy55NjFOwG0> MX2xPVk1ODJ3OR?=
PBMC IL-2 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWPJR|UxRTRwOESgxtEhOS55MDCg{txO NFrmXYwyQTl2MEK1PS=>

... 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
  • 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
Smiles CN1CCN(CC1)C2=NC(=C3C=CC=CC3=N2)C4=C(C(=O)NC4=O)C5=C[NH]C6=C5C=CC=C6

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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