1. TGF-beta/Smad
    Epigenetics
    Autophagy
  2. PKC
    Autophagy

Enzastaurin (Synonyms: LY317615)

Cat. No.: HY-10342 Purity: 99.84%
Data Sheet SDS Handling Instructions

Enzastaurin is a potent PKCβ selective inhibitor with IC50 of 6 nM, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε.

For research use only. We do not sell to patients.
Enzastaurin Chemical Structure

Enzastaurin Chemical Structure

CAS No. : 170364-57-5

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10 mM * 1 mL in DMSO $57 In-stock
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10 mg $70 In-stock
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Enzastaurin is a potent PKCβ selective inhibitor with IC50 of 6 nM, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε.

IC50 & Target

IC50: 6 nM (PKCβ)

In Vitro

Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrates an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 leads to increased levels of β-catenin total protein and β-catenin-mediated transcription. Blocking of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin induces the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreases the mRNA levels and surface expression of CD44[1]. Enzastaurin application results in a marked dose-dependent inhibition of growth in all MM cell lines investigated, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, with IC50 from 0.6-1.6 μM. Enzastaurin direct impacts human tumor cells, inducing apoptosis and suppressing proliferation in cultured tumor cells. Enzastaurin also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308 while having no direct effect on VEGFR phosphorylation[3].

In Vivo

Treatment of xenografts with Enzastaurin and radiation produces greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponds to delayed tumor growth[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01432951 Eli Lilly and Company Solid Tumor|Lymphoma, Malignant November 2011 Phase 1
NCT00452413 Eli Lilly and Company Non-Small Cell Lung Cancer|Malignant Solid Tumor May 2007 Phase 1|Phase 2
NCT00309140 Eli Lilly and Company Neoplasms|Cancer March 2006 Phase 2
NCT00475644 Eli Lilly and Company Lymphoma, Follicular May 2007 Phase 2
NCT00088205 Eli Lilly and Company Mantle-Cell Lymphoma March 2004 Phase 2
NCT00414960 Eli Lilly and Company Lung Cancer November 2006 Phase 2
NCT00452257 Eli Lilly and Company Leukemia, Lymphocytic May 2007 Phase 1
NCT00451555 Eli Lilly and Company Breast Cancer March 2007 Phase 2
NCT01388335 Eli Lilly and Company Solid Tumor|Lymphoma, Malignant August 2011 Phase 1
NCT00503724 Pediatric Brain Tumor Consortium|National Cancer Institute (NCI) Brain and Central Nervous System Tumors|Neuroblastoma June 2007 Phase 1
NCT00509821 Eli Lilly and Company Glioblastoma Multiforme October 2007 Phase 2
NCT00295815 Eli Lilly and Company Glioblastoma January 2006 Phase 3
NCT00415363 Eli Lilly and Company Non Small Cell Lung Cancer|Small Cell Lung Cancer December 2006 Phase 2
NCT00386087 Eli Lilly and Company Breast Neoplasms November 2006 Phase 2
NCT00192114 Eli Lilly and Company Colonic Neoplasms August 2005 Phase 2
NCT00105092 Eli Lilly and Company Non-Small-Cell Lung Carcinoma March 2005 Phase 2
NCT00420381 Eli Lilly and Company|Gynecologic Oncology Group Ovarian Cancer|Neoplasms|Carcinoma January 2007 Phase 2
NCT00466440 Eli Lilly and Company Prostate Cancer June 2007 Phase 2
NCT00428714 Eli Lilly and Company Prostate Cancer January 2007 Phase 2
NCT00108056 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Glioma April 7, 2005 Phase 1
NCT00530621 Eli Lilly and Company Non-small Cell Lung Cancer September 2007 Phase 2
NCT00332202 Eli Lilly and Company Non Hodgkin Lymphoma June 2006 Phase 3
NCT00586508 Eli Lilly and Company|Genentech, Inc. Recurrent Glioblastoma November 2007 Phase 2
NCT00744991 Eli Lilly and Company Cutaneous T-Cell Lymphoma September 2008 Phase 2
NCT00267020 Eli Lilly and Company Pancreatic Neoplasm December 2005 Phase 2
NCT00437294 Eli Lilly and Company Breast Cancer March 2007 Phase 2
NCT01445119 Eli Lilly and Company|National Cancer Institute (NCI) Recurrent Gliomas January 2007 Phase 1
NCT00437268 Eli Lilly and Company Colorectal Cancer|Colorectal Carcinoma|Colorectal Tumor March 2007 Phase 2
NCT00190723 Eli Lilly and Company Malignant Glioma October 2002 Phase 2
NCT00612586 Eli Lilly and Company|Roche Pharma AG Colorectal Cancer February 2008 Phase 2
NCT00718419 Eli Lilly and Company Waldenstrom's Macroglobulinemia|Multiple Myeloma July 2008 Phase 2
NCT00391118 Eli Lilly and Company Ovarian Cancer|Fallopian Tube Neoplasms|Peritoneal Neoplasm November 2006 Phase 2
NCT00709995 Eli Lilly and Company Metastatic Renal Cell Carcinoma June 2008 Phase 2
NCT00407758 Gynecologic Oncology Group|National Cancer Institute (NCI) Ovarian Cancer|Primary Peritoneal Cavity Cancer November 2006 Phase 2
NCT00685633 Eastern Cooperative Oncology Group|National Cancer Institute (NCI) Prostate Cancer December 2008 Phase 2
NCT00536939 Eli Lilly and Company|Genentech, Inc. Breast Cancer November 2007 Phase 2
NCT00451178 Eli Lilly and Company Lymphoma May 2007 Phase 2
NCT00516607 European Organisation for Research and Treatment of Cancer - EORTC Brain and Central Nervous System Tumors July 2007 Phase 1
NCT00402116 Eli Lilly and Company|University of California, San Francisco Glioblastoma|Glioblastoma Multiforme|Gliosarcoma September 2006 Phase 1|Phase 2
NCT00538681 Eli Lilly and Company Lung Cancer September 2007 Phase 2
NCT00533429 Eli Lilly and Company|Genentech, Inc. Non-small Cell Lung Cancer October 2007 Phase 2
NCT00550927 Eli Lilly and Company|National Cancer Institute (NCI) Unspecified Adult Solid Tumor, Protocol Specific November 2006 Phase 1
NCT00469976 Eastern Cooperative Oncology Group|National Cancer Institute (NCI) Lung Cancer June 2007 Phase 2
NCT00542919 Eli Lilly and Company T-Cell Lymphoma|B-Cell Lymphoma November 2007 Phase 2
NCT00052273 Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) Adult|Solid Tumor December 2002 Phase 1
NCT00436280 Eli Lilly and Company Lymphoma, Large Cell, Diffuse February 2007 Phase 2
NCT00308750 Eli Lilly and Company Non-small Cell Lung Cancer March 2006 Phase 2
NCT00042666 Eli Lilly and Company Non-Hodgkin's Lymphoma June 2002 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9395 mL 9.6973 mL 19.3945 mL
5 mM 0.3879 mL 1.9395 mL 3.8789 mL
10 mM 0.1939 mL 0.9697 mL 1.9395 mL
Kinase Assay
[3]

The inhibition of PKCβII, PKCα, PKCε, or PKCγ activity by enzastaurin is determined using a filter plate assay format measuring 33P incorporation into myelin basic protein substrate. Reactions are done in 100 μL reaction volumes in 96-well polystyrene plates with final conditions as follows: 90 mM HEPES (pH 7.5), 0.001% Triton X-100, 4% DMSO, 5 mM MgCl2, 100 μM CaCl2, 0.1 mg/mL phosphatidylserine, 5 μg/mL diacetyl glyerol, 30 μM ATP, 0.005 μCi/μL 33ATP, 0.25 mg/mL myelin basic protein, serial dilutions of enzastaurin (1-2,000 nM), and recombinant human PKCβII, PKCα, PKCε, or PKCγ enzymes (390, 169, 719, or 128 pM, respectively). Reactions are started by addition of the enzyme and incubated at room temperature for 60 minutes. They are then quenched with 10% H3PO4, transferred to multiscreen anionic phosphocellulose 96-well filter plates, incubated for 30 to 90 minutes, filtered and washed with 4 volumes of 0.5% H3PO4 on a vacuum manifold. Scintillation cocktail is added and plates are read on a Microbeta scintillation counter. IC50 values are determined by fitting a three-variable logistic equation to the 10-point dose-response data using ActivityBase 4.0. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[3]

Induction of apoptosis by enzastaurin is measured by nucleosomal fragmentation and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and staining in HCT116 and U87MG 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

515.61

Formula

C₃₂H₂₉N₅O₂

CAS No.

170364-57-5

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.84%

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Enzastaurin
Cat. No.:
HY-10342
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