425637-18-9

Basic information

• Product Name: 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione
• Synonyms: 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione;Sotrastaurin;Sotrastaurin (AEB071);3-(1H-indol-3-yl)-4-(2-(4-methylpiperazin-1-yl)quinazolin-4-yl)-1H-pyrrole-2,5-dione;Dusquetide
• CAS NO: 425637-18-9
• Molecular Formula: C25H22N6O2
• Molecular Weight: 438.48118
• Product Categories: Inhibitors;Smad;TGF-beta
• Mol File: 425637-18-9.mol

Chemical Properties

• Appearance: /
• Density: 1.406
• Solubility: ≥21.9 mg/mL in DMSO; insoluble in H2O; ≥2.55 mg/mL in EtOH with ultrasonic
• PKA: 7.39±0.60(Predicted)
• CAS DataBase Reference: 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione(425637-18-9)
• EPA Substance Registry System: 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione(425637-18-9)

Safety Data

• Hazardous Substances Data: 425637-18-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Sotrastaurin is used as a potent and selective pan-PKC inhibitor for its ability to modulate migration and superoxide anion production by human neutrophils in vitro. Its high specificity for PKCθ makes it a valuable compound in the development of targeted therapies.
Used in Clinical Trials:
Sotrastaurin has been utilized in clinical trials studying the basic science and treatment of various types of cancer, including Uveal Melanoma, Richter Syndrome, Prolymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, and Recurrent Small Lymphocytic Lymphoma. Its role as an immunosuppressant and PKC inhibitor makes it a promising candidate for further research and potential therapeutic applications in oncology.
Used in Research Applications:
As a potent and selective inhibitor of protein kinase C, Sotrastaurin is used in research settings to study the role of PKC in various cellular processes and diseases. Its high specificity for PKCθ allows researchers to investigate the effects of PKC inhibition on cell signaling pathways and other biological functions.

Biological Activity

aeb071 is an inhibitor of protein kinase c (pkc). the pkc inhibitor which can block the t-cell activation has the ability of immune suppression [1].the protein kinase c (pkc) isoforms is very important in cell signaling, proliferation, differentiation, migration, survival, and death. pkc family has many isoforms. among the pkc isoforms, pkc isoforms have basal effect on the t cells’ activation and other immune cell functions [2,3].abe071 is a potent inhibitor of novel and classical pkc isoforms. through the inhibition of pkc, aeb071 can depress the activation and proliferation of t-cell and decrease the production of cytokine.abe071 can also suppress the nk cell activity. ex vivo stimulation of lymphocytes from subjects exposed to single doses of aeb071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and il2 mrna expressionaeb071 is an effective treatment strategy for the cure of autoimmune diseases. according to the psoriasis area severity index (pasi) score, after 2 weeks’ treatment with 300 mg bid aeb071, clinical severity of psoriasis was reduced up to 69% compared with baseline[2,3].

references

[1]. weckbecker g1, pally c, beerli c, et al. effects of the novel protein kinase c inhibitor aeb071 (sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or fty720. transpl int. 2010 may 1;23(5):543-52[2]. skvara h1, dawid m, kleyn e, wolff b, et al. the pkc inhibitor aeb071 may be a therapeutic option for psoriasis. j clin invest. 2008 sep;118(9):3151-9.[3]. matz m1, weber u, mashreghi mf, et al. effects of the new immunosuppressive agent aeb071 on human immune cells. nephrol dial transplant. 2010 jul;25(7):2159-67

Upstream product

• 425638-73-9 2-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-acetamide 
• 425638-74-0 2-(2-chloroquinazolin-4-yl)acetamide 
• 607-68-1 2,4-dichloroquinazoline 
• 86-96-4 1,2,3,4-tetrahydro-quinazoline-2,4-dione 

Downstream Products

• 908351-31-5 3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione acetate 

Relevant articles and documents

Structure-activity relationship and pharmacokinetic studies of sotrastaurin (aeb071), a promising novel medicine for prevention of graft rejection and treatment of psoriasis

Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure-activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4- yl]-pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes

A series of novel maleimide-based inhibitors of protein kinase C(PKC) were designed, synthesized, and evaluated. AEB071 (1) was found to be a potent, selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient immunomodulator, acting via inhibition of early T cell activation. The binding mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by X-ray analysis of 1 bound in the active site of PKCα. 2009 American Chemical Society.