Sotrastaurin

For research use only.

Catalog No.S2791 Synonyms: AEB071

30 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 30 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 M1nrNWZ2dmO2aX;uJGF{e2G7 MVmxNFAhdk1? M1PRelMhcA>? NHzPU4VFVVOR MYnpcohq[mm2czDyVm5CKHO7boTo[ZNqew>? NX3EV2VFOjV4OUGxOVg>
HUVECs  MYjGeY5kfGmxbjDBd5NigQ>? M4r4TFUxOG6P MkHxNUBp M1vsN3Jm\HWlZYOgSHRZNVS{aXfn[ZJm\CCHbnTveIhmdGmjbDDEfZNnfW6ldHnvci=> MYKyOVY{PDV|OB?=
A549 NH[4bYdHfW6ldHnvckBCe3OjeR?= NYDsWYRPOC5zwrFOwG0> M1zzS|I1KGh? M3;OVoRm[3KnYYPld{B1cGVicnXsZZRqfmViUFvDMe6yKGyndnXsJI9vKGOnbHygcYVu[nKjbnWgZ491emWjdHXkJGFUNUmY MXGyOVIyQDF4MR?=
A549 MnHYSpVv[3Srb36gRZN{[Xl? M1zvclAvOcLizszN MV6yOEBp M4HkfZJm\HWlZYOgeIhmKGW6cILld5Nqd25ibHX2[Yx{KG:oIF3NVE0zNCCPTWCtPUBidmRiaX70[YdzcW5izsKx NEnnNpczPTJzOEG2NS=>
A549 NHjDcpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXpOY8xNjIEoN88US=> MluyNlQhcA>? M130RoVvcGGwY3XzJIdzd3e2aDDpcohq[mm2aX;uJINwfHKnYYTl[EB4cXSqIFHTMWlX NHXKdowzPTJzOEG2NS=>
Mel202 M3riTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XLS|AvPSEQvF2= M1L6V|MhcA>? MUXEUXNQ M{HwdIVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 MoS4NlQ2QTV|OEW=
92.1 NVnx[nBHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWKwMlUh|ryP NXnY[FFJOyCq M4XqbmROW09? MVXlcohidmOnczDJVk1qdmS3Y3XkJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fS=> MX[yOFU6PTN6NR?=
OCM3 MnHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWKwMlUh|ryP MYKzJIg> MkjJSG1UVw>? NWL6[VJw\W6qYX7j[ZMhUVJvaX7keYNm\CC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHl? MWiyOFU6PTN6NR?=
Mel202 M3\5Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIixWngxNjVizszN MYqzJIg> MW\EUXNQ MVHpcoNz\WG|ZYOgTXIucW6mdXPl[EBk\WyuIHP5Z4xmKGG{cnXzeOKh MoHBNlQ2QTV|OEW=
92.1 NFLHflRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVywMlUh|ryP NHXW[ZI{KGh? NIO2OWtFVVOR MnnnbY5kemWjc3XzJGlTNWmwZIXj[YQh[2WubDDjfYNt\SCjcoLld5TDqA>? NIezfYEzPDV7NUO4OS=>
OCM3 M3fufWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPvNE42KM7:TR?= MVmzJIg> MknoSG1UVw>? NEPkWFdqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi Ml61NlQ2QTV|OEW=
Jeko-1 MlnxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLvPWpFOC12IN88US=> NVTBXFNCTE2VTx?= NF3USm9qdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MontNlQ{PjJ7M{W=
Mino Mn7ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrKV3NjOC12IN88US=> NFLvXWNFVVOR NF3Z[HVqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MmHqNlQ{PjJ7M{W=
Rec-1 NYXjSHFnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknKNE01KM7:TR?= M1LPemROW09? M133R4lvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> NYnZV2tjOjR|NkK5N|U>
SP49 MoKxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIDZR2gxNTRizszN NYTLeFV5TE2VTx?= NEDQWpJqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MX[yOFM3Ojl|NR?=
Jeko-1 NXfST4wzTnWwY4Tpc44hSXO|YYm= M4fZdFIvPSEQvF5CpC=> MYmxNkBp NFz6bZpFVVOR Ml;3[I94dnKnZ4XsZZRmeyCQRj5OvmIhfGG{Z3X0JIdmdmW| MUCyOFM3Ojl|NR?=
Mino MYHGeY5kfGmxbjDBd5NigQ>? M1Xzc|IvPSEQvF5CpC=> NVfUUVVwOTJiaB?= NEfZTGJFVVOR NHK0cXVld3ewcnXneYxifGW|IF7GMe67SiC2YYLn[ZQh\2WwZYO= M1;sbFI1OzZ{OUO1
Rec-1 MXTGeY5kfGmxbjDBd5NigQ>? NEnkTJIzNjVizszNxsA> NXLUeo5TOTJiaB?= M{fpZmROW09? M{DEfYRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= NHLlPGEzPDN4MkmzOS=>
SP49 NUXWVmtUTnWwY4Tpc44hSXO|YYm= M2PKVlIvPSEQvF5CpC=> MlTyNVIhcA>? M2PteGROW09? NYXCNYFt\G:5boLl[5Vt[XSnczDOSk3PwkJidHHy[4V1KGenbnXz MXWyOFM3Ojl|NR?=
CD3+ T  M1HDdGZ2dmO2aX;uJGF{e2G7 MkLvNE02ODBibl2= NGPVcGUyKGh? NHjrcIFqdmirYnn0d{BPTi4QulKgdIhwe3Cqb4L5cIF1cW:wIHnuJIEh\G:|ZTDk[ZBmdmSnboSgcYFvdmW{ MXyyN|U4OzJ6Mx?=
Mel202 NFzuRWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn34NE02KM7:TR?= M4Pj[|czKGh? MljSSG1UVw>? MYjpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 NYH2cph3OjJ4NUO5Olg>
Omm1.3 MlvQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjBWIUxNTVizszN MXK3NkBp M2i3cmROW09? Ml7hbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NIXab4szOjZ3M{m2PC=>
92.1 NF70ZmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY[wMVUh|ryP M1PleFczKGh? NVrIcnJqTE2VTx?= NWLlUGxmcW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? Mn:4NlI3PTN7Nki=
Mel202 MlvTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\DT4Q2KM7:TR?= NFHCdpAzPCCq MXrEUXNQ MonVbY5lfWOnczDHNUBienKnc4VCpC=> Moj1NlI3PTN7Nki=
Omm1.3 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1G1SFUh|ryP MXyyOEBp MVPEUXNQ MVnpcoR2[2W|IFexJIFzemW|dNMg MoXQNlI3PTN7Nki=
92.1 NXPTUGtzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnyOUDPxE1? NHr1epozPCCq NHO2Z45FVVOR NF60UoZqdmS3Y3XzJGcyKGG{cnXzeOKh MmfXNlI3PTN7Nki=
Mel202 MXPBdI9xfG:|aYOgRZN{[Xl? M4THelUh|ryP NYLsXlNnPzJiaB?= M2[4V2ROW09? NXPWS3U1cW6mdXPld{BieG:ydH;zbZMhe2yrZ3j0cJk> NV;pe3ZJOjJ4NUO5Olg>
Omm1.3 MUPBdI9xfG:|aYOgRZN{[Xl? MUW1JO69VQ>? NF7oUnc4OiCq Mn;DSG1UVw>? MlzlbY5lfWOnczDhdI9xfG:|aYO= MXuyNlY2Ozl4OB?=
92.1 NXvHOIxPSXCxcITvd4l{KEG|c3H5 M1XkVlUh|ryP M120XlczKGh? NHfLUWxFVVOR MmLZbY5lfWOnczDhdI9xfG:|aYOgd4lodmmoY3HueIx6 NHzL[lgzOjZ3M{m2PC=>
Mel202 MY\GeY5kfGmxbjDBd5NigQ>? M4DyS|Uh|ryP MWqyOEBp MlzQbY5pcWKrdIOg[ZhxemW|c3nvckBidmRicHjvd5Bpd3K7bHH0bY9vKG:oIGDLR{Bqe2:ob4Ltdy=> MmjINlI3PTN7Nki=
Omm1.3 NUj2WlZDTnWwY4Tpc44hSXO|YYm= NF70bII2KM7:TR?= NIrqeGozPCCq Mn7zbY5pcWKrdIOg[ZhxemW|c3nvckBidmRicHjvd5Bpd3K7bHH0bY9vKG:oIGDLR{Bqe2:ob4Ltdy=> MmfYNlI3PTN7Nki=
92.1 Mo[ySpVv[3Srb36gRZN{[Xl? MlfwOUDPxE1? NF3iUnMzPCCq NGrh[WFqdmirYnn0d{BmgHC{ZYPzbY9vKGGwZDDwbI9{eGixconsZZRqd25ib3[gVGtEKGm|b3\vdo1{ MYWyNlY2Ozl4OB?=
HBL1 MmTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojWNE4yPi1{MDFOwG0> M2S4N|Uh\A>? NVGwcGI{UUN3ME2wMlUh|ryP MYKyNVMzPDl{MB?=
TMD8 MkLRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTqNE4yPi1{MDFOwG0> MXK1JIQ> M2nvWGlEPTB;MD6yJO69VQ>? NHHUXIozOTN{NEmyNC=>
OCI-Ly10 NYX2ZlUyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17WTFAvOTZvMkCg{txO MWC1JIQ> NWPZbIZ1UUN3ME2xMlMh|ryP NXK5b4trOjF|MkS5NlA>
U2932 MmjnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1nB[FAvOTZvMkCg{txO NWnXN24xPSCm NWS2VHZiUUN3ME2xNEDPxE1? MlX1NlE{OjR7MkC=
OCI-Ly3 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPMe|QxOC5zNj2yNEDPxE1? NHPmN|A2KGR? M4exZmlEPTExvK6yNEDPxE1? MkXVNlE{OjR7MkC=
SuDHL2 M{LNTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHv3ZW0xNjF4LUKwJO69VQ>? MlXBOUBl NYXZflBSUUN3MP-8olIxKM7:TR?= M3TBRVIyOzJ2OUKw
SuDHL4 M2jHO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITtUGsxNjF4LUKwJO69VQ>? NIrhemw2KGR? M{W2NGlEPTExvK6yNEDPxE1? MYCyNVMzPDl{MB?=
DB M1LPc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYPLPZZGOC5zNj2yNEDPxE1? MXW1JIQ> NF\pSndKSzVy78{eNlAh|ryP M2ToOFIyOzJ2OUKw
Jurkat IL-2 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\6[HZKUUN3ME22MlcyKMLzIEOuO|Yh|ryP NVO1e4tROTl7NECyOVk>
PBMC IL-2 NWXEOFJ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnaNFRDUUN3ME20Mlg1KMLzIEGuO|AhKM7:TR?= NWW3NlNvOTl7NECyOVk>

... 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