Sotrastaurin

For research use only.

Catalog No.S2791 Synonyms: AEB071

45 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 45 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 MmrKSpVv[3Srb36gRZN{[Xl? MX:xNFAhdk1? MXuzJIg> MUHEUXNQ NI\EO29qdmirYnn0d{BzWk6DIIP5cpRp\XOrcx?= MV[yOVY6OTF3OB?=
HUVECs  M1TMemZ2dmO2aX;uJGF{e2G7 MoWxOVAxdk1? MVKxJIg> NXizOJFLWmWmdXPld{BFXFhvVILp[4dmemWmIFXu[I91cGWuaXHsJGR6e2[3bnP0bY9v M3TiS|I2PjN2NUO4
A549 NVvrRWdZTnWwY4Tpc44hSXO|YYm= M4XNWlAvOcLizszN M2[0W|I1KGh? M{foOIRm[3KnYYPld{B1cGVicnXsZZRqfmViUFvDMe6yKGyndnXsJI9vKGOnbHygcYVu[nKjbnWgZ491emWjdHXkJGFUNUmY MV6yOVIyQDF4MR?=
A549 NWfrbIZnTnWwY4Tpc44hSXO|YYm= NXHlbm9rOC5zwrFOwG0> NXXTcYRjOjRiaB?= NULiPG5remWmdXPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdHNib3[gUW1RNTJuIF3NVE06KGGwZDDpcpRm\3KrbjFOtlE> Mn7QNlUzOThzNkG=
A549 NFXS[pRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFez[JUxNjIEoN88US=> NVSxdo11OjRiaB?= MV\lcohidmOnczDndo94fGhiaX7obYJqfGmxbjDjc5Rz\WG2ZXSge4l1cCCDUz3JWi=> MljxNlUzOThzNkG=
Mel202 Mnv6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWf6[Ih4OC53IN88US=> NVTDXVFzOyCq Ml;wSG1UVw>? MWXlcohidmOnczDJVk1qdmS3Y3XkJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fS=> NHzNU4ozPDV7NUO4OS=>
92.1 NWDGZ5B7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jWPFAvPSEQvF2= MWqzJIg> NV73O4kzTE2VTx?= MYDlcohidmOnczDJVk1qdmS3Y3XkJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fS=> MVSyOFU6PTN6NR?=
OCM3 NFnsfHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PXbFAvPSEQvF2= MXOzJIg> NV\SRWU1TE2VTx?= M3LHT4VvcGGwY3XzJGlTNWmwZIXj[YQhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6 NETtTpEzPDV7NUO4OS=>
Mel202 MlvYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3n6clAvPSEQvF2= MX:zJIg> Mn;ySG1UVw>? MXTpcoNz\WG|ZYOgTXIucW6mdXPl[EBk\WyuIHP5Z4xmKGG{cnXzeOKh M2Xr[FI1PTl3M{i1
92.1 NYi3SmxVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1H6d|AvPSEQvF2= MXGzJIg> MUnEUXNQ MVXpcoNz\WG|ZYOgTXIucW6mdXPl[EBk\WyuIHP5Z4xmKGG{cnXzeOKh MmnCNlQ2QTV|OEW=
OCM3 NVrWc2J5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDjW3MxNjVizszN NVznU|Y2OyCq MV\EUXNQ NGTuOGNqdmO{ZXHz[ZMhUVJvaX7keYNm\CClZXzsJIN6[2ynIHHydoV{fMLi MnSwNlQ2QTV|OEW=
Jeko-1 Ml7pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfRSWVvOC12IN88US=> M2XvZWROW09? NHnhUFZqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 Mm\nNlQ{PjJ7M{W=
Mino Mn3US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfYSmtKOC12IN88US=> M{PtcmROW09? M4fmUYlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> M4DXcVI1OzZ{OUO1
Rec-1 M3vhU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PJWlAuPCEQvF2= NUT4W2RqTE2VTx?= NWXzRoRLcW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? M1jsfVI1OzZ{OUO1
SP49 NIi5[odIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHUR2kxNTRizszN MoLzSG1UVw>? Ml\KbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> NInZR2UzPDN4MkmzOS=>
Jeko-1 NIKzcnhHfW6ldHnvckBCe3OjeR?= NYfoRWtSOi53IN88UeKh NIr4eG8yOiCq MXjEUXNQ MYDkc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN? NGXlVYYzPDN4MkmzOS=>
Mino M2TGd2Z2dmO2aX;uJGF{e2G7 M2LsTFIvPSEQvF5CpC=> MYOxNkBp MnXNSG1UVw>? MnP1[I94dnKnZ4XsZZRmeyCQRj5OvmIhfGG{Z3X0JIdmdmW| M{KwT|I1OzZ{OUO1
Rec-1 MnPXSpVv[3Srb36gRZN{[Xl? M4W0XVIvPSEQvF5CpC=> Mm\qNVIhcA>? NUPEVW1ETE2VTx?= MV;kc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN? NWXsfJQ5OjR|NkK5N|U>
SP49 Mn3PSpVv[3Srb36gRZN{[Xl? NYTweIp6Oi53IN88UeKh M2e2bFEzKGh? Mo[2SG1UVw>? M{PUdIRwf26{ZXf1cIF1\XNiTl[t{tpDKHSjcnfleEBo\W6ncx?= NYHkWWh6OjR|NkK5N|U>
CD3+ T  MX3GeY5kfGmxbjDBd5NigQ>? MUmwMVUxOCCwTR?= NFjsVncyKGh? MnO3bY5pcWKrdIOgUmYu|rqEIIDoc5NxcG:{eXzheIlwdiCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mn7hNlM2PzN{OEO=
Mel202 M3PMSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX[5SnJwOC13IN88US=> NYfrSJdMPzJiaB?= Mnn0SG1UVw>? M3PnPIlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk> MmLwNlI3PTN7Nki=
Omm1.3 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1L6W|AuPSEQvF2= MXi3NkBp MY\EUXNQ MX\pcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 NIDoXYszOjZ3M{m2PC=>
92.1 M4Hsb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXGwMVUh|ryP MV63NkBp MnvRSG1UVw>? NWnBUHR1cW6qaXLpeJMh[2WubDDndo94fGhiZH;z[UBl\XCnbnTlcpRtgQ>? NUHIfIZtOjJ4NUO5Olg>
Mel202 M{C2dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUG1JO69VQ>? M4PhXlI1KGh? MoDLSG1UVw>? MYPpcoR2[2W|IFexJIFzemW|dNMg M2LoOFIzPjV|OU[4
Omm1.3 NHLYbmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjpTnpiPSEQvF2= M1nGblI1KGh? M1HoT2ROW09? MWXpcoR2[2W|IFexJIFzemW|dNMg MViyNlY2Ozl4OB?=
92.1 MlrwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTFNI82KM7:TR?= MlOyNlQhcA>? MoT1SG1UVw>? M4L0Solv\HWlZYOgS|Eh[XK{ZYP0xsA> M3H4TVIzPjV|OU[4
Mel202 NHHDWGZCeG:ydH;zbZMhSXO|YYm= MoT1OUDPxE1? MYq3NkBp M2PHN2ROW09? NFzDfnNqdmS3Y3XzJIFxd3C2b4Ppd{B{dGmpaITsfS=> NHrZdWgzOjZ3M{m2PC=>
Omm1.3 Mn;MRZBweHSxc3nzJGF{e2G7 M{HmeVUh|ryP M3HRfFczKGh? NIflOIRFVVOR MV3pcoR2[2W|IHHwc5B1d3Orcx?= NFnZb5kzOjZ3M{m2PC=>
92.1 MoTJRZBweHSxc3nzJGF{e2G7 M33oRVUh|ryP MUG3NkBp MYHEUXNQ NV7ie2RqcW6mdXPld{BieG:ydH;zbZMhe2mpbnnmZ4FvfGy7 NYfKN4IyOjJ4NUO5Olg>
Mel202 MVHGeY5kfGmxbjDBd5NigQ>? NH7tOXE2KM7:TR?= NWfo[Fh5OjRiaB?= M17HPYlvcGmkaYTzJIV5eHKnc4Ppc44h[W6mIIDoc5NxcG:{eXzheIlwdiCxZjDQT2MhcXOxZn;ycZM> MlHkNlI3PTN7Nki=
Omm1.3 NUH3[25tTnWwY4Tpc44hSXO|YYm= MVO1JO69VQ>? NGTGZ3AzPCCq M{Dod4lvcGmkaYTzJIV5eHKnc4Ppc44h[W6mIIDoc5NxcG:{eXzheIlwdiCxZjDQT2MhcXOxZn;ycZM> M2PlXFIzPjV|OU[4
92.1 MlOxSpVv[3Srb36gRZN{[Xl? NX3JUmZOPSEQvF2= NEfrV20zPCCq M1zCbolvcGmkaYTzJIV5eHKnc4Ppc44h[W6mIIDoc5NxcG:{eXzheIlwdiCxZjDQT2MhcXOxZn;ycZM> M3vLflIzPjV|OU[4
HBL1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUGwMlE3NTJyIN88US=> MXy1JIQ> NV[5T5Y{UUN3ME2wMlUh|ryP M4DielIyOzJ2OUKw
TMD8 NVrXNW9JT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zMVlAvOTZvMkCg{txO NY\1boh[PSCm MoHnTWM2OD1yLkKg{txO MV:yNVMzPDl{MB?=
OCI-Ly10 M{\3cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rQXVAvOTZvMkCg{txO MYS1JIQ> NHWyRotKSzVyPUGuN{DPxE1? MY[yNVMzPDl{MB?=
U2932 M2TGc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzsbI1NOC5zNj2yNEDPxE1? NUTEepMyPSCm M3zSbWlEPTB;MUCg{txO NIi2OnUzOTN{NEmyNC=>
OCI-Ly3 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2frWFAvOTZvMkCg{txO M3zadlUh\A>? Mof6TWM2OO,:nkKwJO69VQ>? MVGyNVMzPDl{MB?=
SuDHL2 M1q2UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX2wMlE3NTJyIN88US=> MlvROUBl MY\JR|Ux97zgMkCg{txO NHKybG8zOTN{NEmyNC=>
SuDHL4 NGqwUmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO4VFgxNjF4LUKwJO69VQ>? M1P5[VUh\A>? NIXWS3RKSzVy78{eNlAh|ryP NX;sR3I{OjF|MkS5NlA>
DB NEHIdnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoW2NE4yPi1{MDFOwG0> NGq4SJE2KGR? NXjhU|I1UUN3MP-8olIxKM7:TR?= MX6yNVMzPDl{MB?=
Jurkat IL-2 NVjGPZJrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jsN2lEPTB;Nj63NUDDuSB|Lke2JO69VQ>? NIj1bVQyQTl2MEK1PS=>
PBMC IL-2 NXO0cW9TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDNNppKSzVyPUSuPFQhyrFiMT63NEAh|ryP MV[xPVk1ODJ3OR?=

... 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=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 now a wholly owned subsidiary of Pfizer|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