170364-57-5

Usage

Uses

Used in Pharmaceutical Industry:
Enzastaurin (LY317615) is used as a PKCβ-selective inhibitor for suppressing angiogenesis, which is a critical process in the growth and metastasis of various types of cancer. Its ability to inhibit the AKT signaling pathway makes it a promising candidate for the treatment of multiple myeloma and other cancers.
Used in Cancer Research:
In cancer research, Enzastaurin (LY317615) is employed as a tool to study the effects of PKCβ inhibition on tumor growth and progression. Its use in splicing analysis helps researchers understand the molecular mechanisms underlying cancer development and identify potential therapeutic targets.
Used in Drug Development:
Enzastaurin (LY317615) serves as a lead compound in the development of novel therapeutic agents targeting PKCβ. Its potent and selective inhibition of PKCβ makes it a valuable starting point for the design and synthesis of new drugs with improved efficacy and reduced side effects.
Used in Preclinical Studies:
Enzastaurin (LY317615) is used in preclinical studies to evaluate its potential as a therapeutic agent for various types of cancer. These studies involve testing the compound in cell culture and animal models to assess its efficacy, safety, and pharmacokinetic properties.
Used in Neurological Research:
In neurological research, Enzastaurin (LY317615) is used to investigate its effects on amphetamine-stimulated dopamine efflux and blood-brain barrier leakiness. These studies contribute to a better understanding of the role of PKCβ in neurological disorders and the potential of Enzastaurin as a therapeutic agent for conditions such as Parkinson's disease and multiple sclerosis.

Biochem/physiol Actions

Enzastaurin is a potent and PKCβ preferring inhibitor. Also, Enzastaurin inhibits AKT and GSK3β. Enzastaurin acts as anti-angiogenic and antineoplastic agent.

References

1) Graff et al. (2005), The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts; Cancer Res. 65 7462 2) Rizvi et al. (2006) Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines; Mol.Cancer Ther. 5 1783 3) Ouaret and Larsen (2014), Protein kinase Cβ inhibition by enzastaurin leads to mitotic missegregation and preferential cytotoxicity toward colorectal cancer cells with chromosomal instability (CIN); Cell Cycle 13 2697 4) Zestos et al. (2016), PKCβ Inhibitors Attenuate Amphetamine-Stimulated Dopamine Efflux; ACS Chem.Neurosci. 7 757 5) Stranahan et al. (2016), Blood-brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice; J.Cereb.Blood Flow Metab. 36 2108

InChI:InChI=1/C32H29N5O2/c1-35-19-25(23-9-2-4-11-27(23)35)29-30(32(39)34-31(29)38)26-20-37(28-12-5-3-10-24(26)28)22-13-16-36(17-14-22)18-21-8-6-7-15-33-21/h2-12,15,19-20,22H,13-14,16-18H2,1H3,(H,34,38,39)

Upstream product

• 150114-41-3 1-methylindole-3-acetamide 
• 616898-64-7 oxo-[1-(1-pyridin-2-ylmethyl-piperidin-4-yl)-1H-indol-3-yl]-oxo-acetic acid methyl ester 
• 118511-81-2 1-(4-piperidinyl)-1H-indole 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 496-15-1 1-indoline 
• 1002115-95-8 oxo-[1-(1-pyridin-2-ylmethyl-piperidin-4-yl)-1H-indol-3-yl]-acetyl chloride 
• 16382-38-0 1-methylindole-3-glyoxylyl chloride 
• 603-76-9 1-methylindole 
• 31106-82-8 2-(bromomethyl)pyridine hydrobromide 
• 170364-60-0 LY 326020 
• 616898-73-8 4-(3-carbamoylmethyl-2,3-dihydro-indol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester 
• 616898-59-0 4-(3-carbamoylmethyl-1-indol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester 
• 616898-71-6 2-(1-(1-(pyridin-2-ylmethyl)piperidin-4-yl)indolin-3-yl)acetamide 
• 158867-78-8 N,N-bis(2-ethoxycarbonylethyl)-N-(2-pyridilmethyl)amine 

Downstream Products

• 359017-79-1 Enzastaurin hydrochloride 

Relevant academic research and scientific papers

Acyclic N-(azacycloalkyl)bisindolylmaleimides: Isozyme selective inhibitors of PKCβ

The synthesis and structure-activity relationship (SAR) trends of a new class of N-(azacycloalkyl)bisindolylmaleimides 1, acyclic derivatives of staurosporine, is described. The representative compound for this series (1e) exhibits an IC50 of 40-50 nM against the human PKCβ1 and PKCβ2 isozymes and selectively inhibits the PKCβ isozymes in comparison to other PKC isozymes (α, γ, δ, ε, λ, and η). The series is also kinase selective for PKC in comparison to other ATP-dependent kinases. A comparison of the PKC isozyme and kinase activity of the series is made to the kinase inhibitor staurosporine.

Synthesis of the tritiated isotopomers of enzastaurin and its N-des-pyridylmethyl metabolite for use in ADME studies

Enzastaurin (3-(1-methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4- piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione, 1), an agent with potential utility in the treatment of solid tumors, is currently in phase II clinical trials. Enzastaurin undergoes metabolism in vitro and in vivo to several products of oxidative metabolism, the major one of which is 3-(1-methyl-1H- indol-3-yl)-4-(1-piperidin-4-yl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (2). In a model study, the attempted synthesis 1-[2H] by reaction of 1 with deuterium gas in the presence of Ir[(COD)(Cy3P)pyr]PF6 (Crabtree's catalyst) was unsuccessful. Alternatively, it was decided to prepare tritiated 2 as both a final product and the starting material for the tritiation of 1. We have reported herein a route that was developed for use in the preparation of tritium-labeled 2-[3H] and its successful conversion to 1-[3H]. Copyright

[11C]Enzastaurin, the first design and radiosynthesis of a new potential PET agent for imaging of protein kinase C

Enzastaurin (LY317615) is a potent and selective protein kinase C (PKC) inhibitor with an IC50 value of ～6 nM. [11C] Enzastaurin (3-(1-[11C]methyl-1H-indol-3-yl)-4-[1-[1-(2- pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of PKC, was first designed and synthesized in 20-25% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide.

CRYSTALLINE 2,5-DIONE-3-(1-METHYL-1H-INDOL-3-YL)-4-[1-(PYRIDIN-2-YLMETHYL)PIPERIDIN-4-YL]-1H-INDOL-3-YL]-1H-PYRROLE MONO-HYDROCHLORIDE

The present invention relates to crystalline 2,5-dione-3-(1-methyl-1H-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl]-1H-pyrrole mono-hydrochloride salt, a pharmaceutical formulation containing said salt and to methods for treating can

Strategies for the synthesis of N-(azacycloalkyl)bisindolylmaleimides: Selective inhibitors of PKCβ

N-(Azacycloalkyl)bisindolylmaleimides 1 have been identified to be selective inhibitors of PKCβ. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for prepa