Sotrastaurin

For research use only.

Catalog No.S2791 Synonyms: AEB071

37 publications

Sotrastaurin Chemical Structure

CAS No. 425637-18-9

Sotrastaurin (AEB071) 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 37 publications

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Biological Activity

Description Sotrastaurin (AEB071) 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 NHTFRXJHfW6ldHnvckBCe3OjeR?= MYqxNFAhdk1? M1TnRVMhcA>? MX3EUXNQ MlXvbY5pcWKrdIOgdnJPSSC|eX70bIV{cXN? MU[yOVY6OTF3OB?=
HUVECs  MXTGeY5kfGmxbjDBd5NigQ>? NWnrZVVHPTBybl2= NUH5bmF2OSCq NVjqXXFtWmWmdXPld{BFXFhvVILp[4dmemWmIFXu[I91cGWuaXHsJGR6e2[3bnP0bY9v M{\hS|I2PjN2NUO4
A549 NIqyfnhHfW6ldHnvckBCe3OjeR?= MVSwMlHDqM7:TR?= MVeyOEBp NULoZmpP\GWlcnXhd4V{KHSqZTDy[YxifGm4ZTDQT2Mu|rFibHX2[Ywhd25iY3XscEBu\W2kcnHu[UBkd3S{ZXH0[YQhSVNvSW[= NYHoVJRVOjV{MUixOlE>
A549 NUDJVYZqTnWwY4Tpc44hSXO|YYm= MnrtNE4yyqEQvF2= NVzySnU2OjRiaB?= NXvySJpoemWmdXPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdHNib3[gUW1RNTJuIF3NVE06KGGwZDDpcpRm\3KrbjFOtlE> NHjuU2QzPTJzOEG2NS=>
A549 MkTFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHOybFAxNjIEoN88US=> NGDpWIMzPCCq NGHadmZmdmijbnPld{Boem:5dHigbY5pcWKrdHnvckBkd3S{ZXH0[YQhf2m2aDDBV{1KXg>? NYH3R2R[OjV{MUixOlE>
Mel202 NI[4WWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTQNJNnOC53IN88US=> NHTs[G4{KGh? MVHEUXNQ NEnnT2tmdmijbnPld{BKWi2rbnT1Z4VlKHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gQ>? NXzIXm9zOjR3OUWzPFU>
92.1 NYLETnhWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIixPZExNjVizszN NWPCdndCOyCq MlKySG1UVw>? M1LwPYVvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 M4PXeFI1PTl3M{i1
OCM3 NH7LZWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYiyW4pUOC53IN88US=> NIC5Roc{KGh? NYTsN|JTTE2VTx?= NGTYeGdmdmijbnPld{BKWi2rbnT1Z4VlKHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gQ>? M1m5PVI1PTl3M{i1
Mel202 MmPBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFy3WIIxNjVizszN MmfTN{Bp M{TzcWROW09? MWrpcoNz\WG|ZYOgTXIucW6mdXPl[EBk\WyuIHP5Z4xmKGG{cnXzeOKh M4jhTlI1PTl3M{i1
92.1 MkW5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVL4O|F6OC53IN88US=> NFzvb2Y{KGh? MV3EUXNQ M4PVXIlv[3KnYYPld{BKWi2rbnT1Z4VlKGOnbHygZ5lkdGViYYLy[ZN1yqB? M3q1dlI1PTl3M{i1
OCM3 MlHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1f0dVAvPSEQvF2= M{X1UlMhcA>? NV6xdG1KTE2VTx?= NGfDNHVqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi NUe5NmZQOjR3OUWzPFU>
Jeko-1 NXm2bFVIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTteWFlOC12IN88US=> MlnSSG1UVw>? MVLpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 NGKzUW8zPDN4MkmzOS=>
Mino NX\rPIFHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXewMVQh|ryP M3m3WGROW09? NEHl[WVqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 M3rjU|I1OzZ{OUO1
Rec-1 NXfHUlB2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkPlNE01KM7:TR?= NVz5TlNUTE2VTx?= MWXpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 MYqyOFM3Ojl|NR?=
SP49 NUHUTXBsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHUN4pWOC12IN88US=> NVXiT3lsTE2VTx?= M1\YWIlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> NHzIXFQzPDN4MkmzOS=>
Jeko-1 NIjPdFRHfW6ldHnvckBCe3OjeR?= NFK4R|EzNjVizszNxsA> MkjmNVIhcA>? MVjEUXNQ NHXmWohld3ewcnXneYxifGW|IF7GMe67SiC2YYLn[ZQh\2WwZYO= NVvufZNyOjR|NkK5N|U>
Mino M4nYPGZ2dmO2aX;uJGF{e2G7 MW[yMlUh|ryPwrC= MVSxNkBp NVzuW|RXTE2VTx?= NEjXdWpld3ewcnXneYxifGW|IF7GMe67SiC2YYLn[ZQh\2WwZYO= MljCNlQ{PjJ7M{W=
Rec-1 MXHGeY5kfGmxbjDBd5NigQ>? MmqxNk42KM7:TdMg NUXQTnB{OTJiaB?= NXLwVWM3TE2VTx?= MY\kc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN? M2Ptc|I1OzZ{OUO1
SP49 MULGeY5kfGmxbjDBd5NigQ>? MWiyMlUh|ryPwrC= NEfscpAyOiCq NUP5bYEzTE2VTx?= NWXPPYtu\G:5boLl[5Vt[XSnczDOSk3PwkJidHHy[4V1KGenbnXz MmTENlQ{PjJ7M{W=
CD3+ T  M4\uT2Z2dmO2aX;uJGF{e2G7 MX:wMVUxOCCwTR?= M2Xnb|EhcA>? M33kcolvcGmkaYTzJG5HNc78QjDwbI9{eGixconsZZRqd25iaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MWqyN|U4OzJ6Mx?=
Mel202 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHZNE02KM7:TR?= NXn5PGYyPzJiaB?= NEPRUJFFVVOR NHPC[oZqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 NXfqSmF6OjJ4NUO5Olg>
Omm1.3 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rSUFAuPSEQvF2= M{LUUVczKGh? M1vv[2ROW09? NV\qT4d2cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NV3EWYVIOjJ4NUO5Olg>
92.1 M1vE[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlrqNE02KM7:TR?= M1r5blczKGh? MlLvSG1UVw>? MoqzbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> M2TtUlIzPjV|OU[4
Mel202 M2LmTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;VTW5oPSEQvF2= MVGyOEBp NV30[5RMTE2VTx?= M{e1colv\HWlZYOgS|Eh[XK{ZYP0xsA> M3zO[FIzPjV|OU[4
Omm1.3 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXS1JO69VQ>? NXPvboI2OjRiaB?= MlfvSG1UVw>? Mn\tbY5lfWOnczDHNUBienKnc4VCpC=> Mkf4NlI3PTN7Nki=
92.1 MnvpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\Y[I02KM7:TR?= MYWyOEBp M12xfmROW09? M3LoTIlv\HWlZYOgS|Eh[XK{ZYP0xsA> MoHsNlI3PTN7Nki=
Mel202 MYLBdI9xfG:|aYOgRZN{[Xl? NV\adm1pPSEQvF2= M2nEWFczKGh? NHjlbo9FVVOR NV3DdXRycW6mdXPld{BieG:ydH;zbZMhe2yrZ3j0cJk> MmXGNlI3PTN7Nki=
Omm1.3 M{TTfGFxd3C2b4Ppd{BCe3OjeR?= M4\CSVUh|ryP MnrVO|IhcA>? NWi2V4c1TE2VTx?= NF7zVJdqdmS3Y3XzJIFxd3C2b4Ppdy=> NXfYbldOOjJ4NUO5Olg>
92.1 M17jOGFxd3C2b4Ppd{BCe3OjeR?= NUi3bHpwPSEQvF2= NYf4U3VrPzJiaB?= M3PT[mROW09? Mm\3bY5lfWOnczDhdI9xfG:|aYOgd4lodmmoY3HueIx6 NFrQXpAzOjZ3M{m2PC=>
Mel202 MVTGeY5kfGmxbjDBd5NigQ>? NG\3eYY2KM7:TR?= MV:yOEBp NXXs[YExcW6qaXLpeJMh\XiycnXzd4lwdiCjbnSgdIhwe3Cqb4L5cIF1cW:wIH;mJHBMSyCrc3;mc5Juew>? NXXz[pBsOjJ4NUO5Olg>
Omm1.3 NYfldWdSTnWwY4Tpc44hSXO|YYm= NFXyPJg2KM7:TR?= M4q4NVI1KGh? NV;EOJd2cW6qaXLpeJMh\XiycnXzd4lwdiCjbnSgdIhwe3Cqb4L5cIF1cW:wIH;mJHBMSyCrc3;mc5Juew>? MWGyNlY2Ozl4OB?=
92.1 MoLVSpVv[3Srb36gRZN{[Xl? NH31TZY2KM7:TR?= MWqyOEBp Ml;LbY5pcWKrdIOg[ZhxemW|c3nvckBidmRicHjvd5Bpd3K7bHH0bY9vKG:oIGDLR{Bqe2:ob4Ltdy=> MXOyNlY2Ozl4OB?=
HBL1 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXewMlE3NTJyIN88US=> NHnEXIM2KGR? MVfJR|UxRTBwNTFOwG0> NX\OSI96OjF|MkS5NlA>
TMD8 NF7yfYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYK1RYo1OC5zNj2yNEDPxE1? MoX0OUBl MVvJR|UxRTBwMjFOwG0> MmLXNlE{OjR7MkC=
OCI-Ly10 NF\KU3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrPNE4yPi1{MDFOwG0> MkXROUBl MnHYTWM2OD1zLkOg{txO MWWyNVMzPDl{MB?=
U2932 M13z[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLONm1iOC5zNj2yNEDPxE1? NFjCN5I2KGR? MWXJR|UxRTFyIN88US=> NF\UdJozOTN{NEmyNC=>
OCI-Ly3 NFPkVYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{DsZ|AvOTZvMkCg{txO MVu1JIQ> Mn21TWM2OO,:nkKwJO69VQ>? M3;rclIyOzJ2OUKw
SuDHL2 NIq0UFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nZeFAvOTZvMkCg{txO NF3tXYM2KGR? M162dWlEPTExvK6yNEDPxE1? MYWyNVMzPDl{MB?=
SuDHL4 NV7KbWUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXywMlE3NTJyIN88US=> M3j1RVUh\A>? NVj0S3RZUUN3MP-8olIxKM7:TR?= MYeyNVMzPDl{MB?=
DB NHrSbolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPNdVgxNjF4LUKwJO69VQ>? MlH2OUBl Ml;ETWM2OO,:nkKwJO69VQ>? MmGzNlE{OjR7MkC=
Jurkat IL-2 NVnnU3dOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M37GZWlEPTB;Nj63NUDDuSB|Lke2JO69VQ>? NVLr[odwOTl7NECyOVk>
PBMC IL-2 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\UOFM5UUN3ME20Mlg1KMLzIEGuO|AhKM7:TR?= NFi4U4IyQTl2MEK1PS=>

... 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)
Water Insoluble
Ethanol '2 mg/mL
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=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02273219 Unknown status 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.

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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