Sotrastaurin

Catalog No.S2791

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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Sotrastaurin Chemical Structure

Sotrastaurin Chemical Structure
Molecular Weight: 438.48

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Product Description

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.
Targets PKCθ [1]
(Cell-free assay)
PKCβ1 [1]
(Cell-free assay)
PKCα [1]
(Cell-free assay)
PKCη [1]
(Cell-free assay)

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IC50 0.22 nM(Ki) 0.64 nM(Ki) 0.95 nM(Ki) 1.8 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
T cellNGfwW2JHfW6ldHnvckBCe3OjeR?=MUOxNFAhdk1?NEHRNI8{KGh?Mo\5SG1UVw>?M3LNZolvcGmkaYTzJJJTVkFic4nueIhme2m|NH7tW3UzPTZ7MUG1PC=>
HUVECs NV3Rd3JkTnWwY4Tpc44hSXO|YYm=NXv1OpBjPTBybl2=MkfWNUBpNXXzVGhtWmWmdXPld{BFXFhvVILp[4dmemWmIFXu[I91cGWuaXHsJGR6e2[3bnP0bY9vNGPmfZQzPTZ|NEWzPC=>
A549MkTLSpVv[3Srb36gRZN{[Xl?MWWwMlHDqM7:TR?=NUD2bpEyOjRiaB?=NEDveVBl\WO{ZXHz[ZMhfGinIILlcIF1cX[nIGDLR{3PuSCuZY\lcEBwdiClZXzsJI1mdWK{YX7lJINwfHKnYYTl[EBCWy2LVh?=NInXfmkzPTJzOEG2NS=>
A549MWDGeY5kfGmxbjDBd5NigQ>?Mo\BNE4yyqEQvF2=MUGyOEBpMmLYdoVlfWOnczD0bIUh\XiycnXzd4lwdiCuZY\lcJMhd2ZiTV3QMVItKE2PUD25JIFv\CCrboTl[5JqdiEQskG=M2KzPFI2OjF6MU[x
A549MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlvJNE4yyqEQvF2=M3;4cFI1KGh?NGfwTYdmdmijbnPld{Boem:5dHigbY5pcWKrdHnvckBkd3S{ZXH0[YQhf2m2aDDBV{1KXg>?MV6yOVIyQDF4MR?=
Mel202MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYmwMlUh|ryPNIL1VWk{KGh?MV7EUXNQNEXOZY5mdmijbnPld{BKWi2rbnT1Z4VlKHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gQ>?NXqzdIhKOjR3OUWzPFU>
92.1NV34WpIzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIPD[pkxNjVizszNNHP5Rmo{KGh?MoewSG1UVw>?NVLvdGsx\W6qYX7j[ZMhUVJvaX7keYNm\CC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHl?NGq4VFQzPDV7NUO4OS=>
OCM3M3zXSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYOwMlUh|ryPMlTSN{BpNWOxXIF1TE2VTx?=NYfPfnJM\W6qYX7j[ZMhUVJvaX7keYNm\CC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHl?M4e3elI1PTl3M{i1
Mel202MmPKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWKwMlUh|ryPMVqzJIg>MnnwSG1UVw>?MlXhbY5kemWjc3XzJGlTNWmwZIXj[YQh[2WubDDjfYNt\SCjcoLld5TDqA>?MnGzNlQ2QTV|OEW=
92.1NFnuPIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MnK1NE42KM7:TR?=NU\B[2lrOyCqNFqyeFVFVVORMnzhbY5kemWjc3XzJGlTNWmwZIXj[YQh[2WubDDjfYNt\SCjcoLld5TDqA>?NEnYdG8zPDV7NUO4OS=>
OCM3Mmm5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NI[5VlcxNjVizszNMl;NN{BpMmXOSG1UVw>?NUPHUld[cW6lcnXhd4V{KEmULXnu[JVk\WRiY3XscEBkgWOuZTDhdpJme3UEoB?=NYfnN2JoOjR3OUWzPFU>
Jeko-1MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3uzN|AuPCEQvF2=M2j2W2ROW09?MXzpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5MWOyOFM3Ojl|NR?=
MinoNVvhV4ZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWjjXI9POC12IN88US=>NF7sdIVFVVORMYLpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5NEX4d5MzPDN4MkmzOS=>
Rec-1MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M{T5NVAuPCEQvF2=MoDtSG1UVw>?M3vPVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGSxc3Wg[IVx\W6mZX70cJk>MXSyOFM3Ojl|NR?=
SP49NXTjR3BIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHXoXYExNTRizszNNEjQOZNFVVORMoDEbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=>M37iWVI1OzZ{OUO1
Jeko-1MYDGeY5kfGmxbjDBd5NigQ>?NX\KcoFPOi53IN88UeKhM3HtO|EzKGh?NFfmWlJFVVORNF:5eGFld3ewcnXneYxifGW|IF7GMe67SiC2YYLn[ZQh\2WwZYO=MonQNlQ{PjJ7M{W=
MinoMn3tSpVv[3Srb36gRZN{[Xl?NGPZcogzNjVizszNxsA>MYmxNkBpM2jWdmROW09?MWXkc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN?NIXPPIIzPDN4MkmzOS=>
Rec-1MV\GeY5kfGmxbjDBd5NigQ>?MoTXNk42KM7:TdMgM{XTfFEzKGh?MnjNSG1UVw>?MV7kc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN?NI\xW44zPDN4MkmzOS=>
SP49NUHSPHRkTnWwY4Tpc44hSXO|YYm=M4\5XVIvPSEQvF5CpC=>MoDJNVIhcA>?NYHFPIhFTE2VTx?=MYPkc5dvemWpdXzheIV{KE6ILd86RkB1[XKpZYSg[4Vv\XN?Mmr6NlQ{PjJ7M{W=
CD3+ T MXnGeY5kfGmxbjDBd5NigQ>?MWOwMVUxOCCwTR?=MYmxJIg>NEfqZZhqdmirYnn0d{BPTi4QulKgdIhwe3Cqb4L5cIF1cW:wIHnuJIEh\G:|ZTDk[ZBmdmSnboSgcYFvdmW{NXnrVllsOjN3N{OyPFM>
Mel202MljiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3[2UVAuPSEQvF2=Mn:1O|IhcA>?MkGzSG1UVw>?MkXTbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=>MnzTNlI3PTN7Nki=
Omm1.3NGTDWXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmDPNE02KM7:TR?=MWC3NkBpNH:4WotFVVORNF2wNVFqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6NHPTeYozOjZ3M{m2PC=>
92.1NV3Je29XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NEHSOGcxNTVizszNMmfEO|IhcA>?MUDEUXNQMmLSbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=>NGHmVVgzOjZ3M{m2PC=>
Mel202Ml\oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVm1JO69VQ>?MW[yOEBpNHXwO2pFVVORMVjpcoR2[2W|IFexJIFzemW|dNMgNV3wVYJOOjJ4NUO5Olg>
Omm1.3MoXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVy1JO69VQ>?MV[yOEBpMVPEUXNQNVH1epBDcW6mdXPld{BIOSCjcoLld5TDqA>?NGjWSI4zOjZ3M{m2PC=>
92.1M1\4[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYG1JO69VQ>?NGe0OZMzPCCqNGDSSo1FVVORNEHaOHVqdmS3Y3XzJGcyKGG{cnXzeOKhMn:4NlI3PTN7Nki=
Mel202M2j4b2Fxd3C2b4Ppd{BCe3OjeR?=NHrDdZc2KM7:TR?=MYO3NkBpNVz0NmF[TE2VTx?=NIP5OlhqdmS3Y3XzJIFxd3C2b4Ppd{B{dGmpaITsfS=>MoDBNlI3PTN7Nki=
Omm1.3MXfBdI9xfG:|aYOgRZN{[Xl?NWrWSGFIPSEQvF2=NV3o[ZFvPzJiaB?=M3vafGROW09?MlXCbY5lfWOnczDhdI9xfG:|aYO=NHPyenAzOjZ3M{m2PC=>
92.1MXjBdI9xfG:|aYOgRZN{[Xl?MVq1JO69VQ>?M1nlVlczKGh?MnXlSG1UVw>?M2j0Uolv\HWlZYOgZZBweHSxc3nzJJNq\26rZnPhcpRtgQ>?NV3He4M1OjJ4NUO5Olg>
Mel202MWnGeY5kfGmxbjDBd5NigQ>?NI[1R|Y2KM7:TR?=NXXRSlJOOjRiaB?=NHLyOphqdmirYnn0d{BmgHC{ZYPzbY9vKGGwZDDwbI9{eGixconsZZRqd25ib3[gVGtEKGm|b3\vdo1{MVKyNlY2Ozl4OB?=
Omm1.3MmjnSpVv[3Srb36gRZN{[Xl?M133R|Uh|ryPNGHRUVUzPCCqNXfvPXBicW6qaXLpeJMh\XiycnXzd4lwdiCjbnSgdIhwe3Cqb4L5cIF1cW:wIH;mJHBMSyCrc3;mc5Juew>?M4LnN|IzPjV|OU[4
92.1MY\GeY5kfGmxbjDBd5NigQ>?MXW1JO69VQ>?M1Hu[FI1KGh?M4D3c4lvcGmkaYTzJIV5eHKnc4Ppc44h[W6mIIDoc5NxcG:{eXzheIlwdiCxZjDQT2MhcXOxZn;ycZM>MnLPNlI3PTN7Nki=
HBL1MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFSzOVMxNjF4LUKwJO69VQ>?NWnhNGRTPSCmNWq2WHZGUUN3ME2wMlUh|ryPNWfJfZd6OjF|MkS5NlA>
TMD8NGXaOZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIDQb5AxNjF4LUKwJO69VQ>?NELBXmg2KGR?NXjEUFBjUUN3ME2wMlIh|ryPNIrtZWIzOTN{NEmyNC=>
OCI-Ly10NEfrXJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{m1TVAvOTZvMkCg{txOM3TnWVUh\A>?NFG4TGNKSzVyPUGuN{DPxE1?NXLqcWZmOjF|MkS5NlA>
U2932MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYKwMlE3NTJyIN88US=>M3;MTlUh\A>?M4m1dWlEPTB;MUCg{txONEjyTJMzOTN{NEmyNC=>
OCI-Ly3MnvaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MonKNE4yPi1{MDFOwG0>NF;SW5o2KGR?MnzpTWM2OO,:nkKwJO69VQ>?MkK4NlE{OjR7MkC=
SuDHL2MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NWjBZm9TOC5zNj2yNEDPxE1?MVG1JIQ>NUiwUHVYUUN3MP-8olIxKM7:TR?=NWG3eZF2OjF|MkS5NlA>
SuDHL4MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHnISZMxNjF4LUKwJO69VQ>?MXq1JIQ>NXO3UmxHUUN3MP-8olIxKM7:TR?=MYqyNVMzPDl{MB?=
DBM{T6NWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NX;CeZhoOC5zNj2yNEDPxE1?M4\5flUh\A>?MnW5TWM2OO,:nkKwJO69VQ>?MXqyNVMzPDl{MB?=
Jurkat IL-2MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NELVSnhKSzVyPU[uO|EhyrFiMz63OkDPxE1?M2nxN|E6QTRyMkW5
PBMC IL-2NFXvbWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1m1ZmlEPTB;ND64OEDDuSBzLkewJEDPxE1?Mm\VNVk6PDB{NUm=

... Click to View More Cell Line Experimental Data

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]
Features Unlike former PKC inhibitors, Sotrastaurin does not enhance apoptosis of murine T-cell blasts in a model of activation-induced cell death.

Protocol(Only for Reference)

Kinase Assay: [1]

Protein Kinase Assays Classical and novel PKC isotypes are assayed by scintillation proximity assay technology. In brief, the assay is performed in 20 mM Tris-HCl buffer, pH 7.4, and 0.1% bovine serum albumin by incubating 1.5 μM of the peptide substrate with 10 μM [33P]ATP, 10 mM Mg (NO3)2, 0.2 mM CaCl2, and PKC at a protein concentration varying from 25 to 400 ng/mL, and lipid vesicles containing 30 mol% phosphatidylserine, 5 mol% diacylglycerol (DAG), and 65 mol% phosphatidylcholine at a final lipid concentration of 0.5 μM. Incubation is performed for 60 min at room temperature. The reaction is stopped by adding 50 μl of a mixture containing 100 mM EDTA, 200 μM ATP, 0.1% Triton X-100, and 0.375 μg/well streptavidin-coated scintillation proximity assay beads in PBS without Ca2+ and Mg2+. Incorporated radioactivity is measured in a MicroBetaTrilux counter for 1 min.

Animal Study: [3]

Animal Models male Wistar/F rats
Formulation Saline
Dosages 10 mg/kg and 30 mg/kg
Administration Orally administrated

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Evenou JP, et al. J Pharmacol Exp Ther, 2009, 330(3), 792-801.

[2] Naylor TL, et al. Cancer Res, 2011, 71(7), 2643-2653.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-06-25)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02273219 Recruiting Uveal Melanoma Richard D. Carvajal|Columbia University November 2014 Phase 1
NCT01854606 Active, not recruiting CD79 Mutant or ABC-subtype Diffuse Large B-Cell Lymphoma Novartis Pharmaceuticals|Novartis December 2013 Phase 1|Phase 2
NCT01801358 Terminated Uveal Melanoma Array BioPharma August 2013 Phase 1|Phase 2
NCT01430416 Recruiting Uveal Melanoma Novartis Pharmaceuticals|Novartis December 2011 Phase 1
NCT01402440 Terminated Diffuse Large B-Cell Lymphoma Novartis Pharmaceuticals|Novartis November 2011 Phase 1

view more

Chemical Information

Download Sotrastaurin SDF
Molecular Weight (MW) 438.48
Formula

C25H22N6O2

CAS No. 425637-18-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms AEB071
Solubility (25°C) * In vitro DMSO 87 mg/mL (198.41 mM)
Ethanol 2 mg/mL (4.56 mM)
Water <1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+ddH2O 10mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 3-(1H-indol-3-yl)-4-(2-(4-methylpiperazin-1-yl)quinazolin-4-yl)-1H-pyrrole-2,5-dione

Customer Product Validation(2)


Click to enlarge
Rating
Source Cancer Cell, 2015, 27(3): 397-408 . Sotrastaurin purchased from Selleck
Method Western Blot
Cell Lines H3122 & MGH006 cells
Concentrations 0.3 µM
Incubation Time
Results The resistance induced by PMA in H3122 and MGH006 was reversed by sotrastaurin, consistent with a PKC-dependent phenotype.

Click to enlarge
Rating
Source Proc Natl Acad Sci USA, 2014, 111(15): E1528-37. Sotrastaurin purchased from Selleck
Method Flow Cytometry
Cell Lines J-Lat A2 cells
Concentrations 0-1.78 nM
Incubation Time 24 h
Results AUY922 and sotrastaurin had an additive or modest synergistic effect on HIV-1 reactivation, such that AUY922 at a concentration of 15 nM reached an IC90 in combination with as little as 60 nM sotrastaurin, which corresponds to 1/330th of the concentration of sotrastaurin used in the phase II trial.

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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