Enzastaurin

SKU: orb1300907

Description

Enzastaurin (LY317615) is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, exhibiting 6-20 fold selectivity over PKCα, γ, and ε isoforms. It has been widely used in preclinical cancer research, including in vitro cell studies and in vivo tumor models, to investigate angiogenesis and cell signaling pathways.

Research Area

Cell Biology, Neuroscience

Key Properties

• CAS Number: 170364-57-5
• MW: 515.61
• Purity: >98%
• Formula: C₃₂H₂₉N₅O₂
• SMILES: O=C1C(C=2C=3C(N(C2)C4CCN(CC5=CC=CC=N5)CC4)=CC=CC3)=C(C(=O)N1)C=6C=7C(N(C)C6)=CC=CC7
• Target: Kinase
• Solubility: Soluble in DMSO (up to 7 mg/ml with warming)

Bioactivity

• Target IC50:
  PKCγ:83 nM|PKCα:39 nM|PKCε:110 nM|PKCβ:6 nM
• In Vivo:
  The combined treatment of xenografts with Enzastaurin and radiation resulted in a greater reduction in microvessel density compared to either treatment alone, correlating with delayed tumor growth.
• In Vitro:
  Application of Enzastaurin consistently leads to significant dose-dependent growth inhibition in a variety of MM cell lines, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, achieving half-maximal inhibitory concentrations (IC50) ranging from 0.6 to 1.6 μM. This compound directly targets human tumor cells by promoting apoptosis and hindering cell proliferation. It specifically reduces the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308, while not affecting VEGFR phosphorylation. Furthermore, Enzastaurin elevates apoptosis rates in CTCL's malignant lymphocytes and shows increased cytotoxicity when used alongside GSK3 inhibitors. A notable synergy is observed when Enzastaurin is combined with the GSK3 inhibitor AR-A014418, leading to raised levels of β-catenin total protein and its mediated transcription. Blocking this transcription or reducing β-catenin expression through shRNA achieves similar cytotoxic effects to the Enzastaurin and AR-A014418 combination. This treatment pair also notably diminishes mRNA levels and surface expression of CD44.
• Cell Research:
  Induction of apoptosis by enzastaurin is measured by nucleosomal fragmentation and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and staining in HCT116 and U87 mg cell lines. Briefly, 5 × 103 cells are plated per well in 96-well plates (1% FBS-supplemented media conditions), incubated with or without Enzastaurin for 48 to 72 hours. The absorbance values are normalized to those from control-treated cells to derive a nucleosomal enrichment factor at all concentrations as per the manufacturer's protocol. The concentrations studied ranges from 0.1 to 10 μM. In situ TUNEL staining is assayed with the In situ Cell Death Detection, Fluorescein kit. Cells (7.5 ×104) are plated per well in 6-well plates and incubated 72 hours in 1% FBS-supplemented media Enzastaurin. Fluorescein-labeled DNA strand breaks are detected with the BD epics flow cytometer. Ten thousand, single-cell, FITC-staining events are collected for each test. (Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY-317615

Compound Identifiers

PubChem CID

176167