Enzastaurin (LY317615)

For research use only.

Catalog No.S1055

36 publications

Enzastaurin (LY317615) Chemical Structure

CAS No. 170364-57-5

Enzastaurin (LY317615) is a potent PKCβ selective inhibitor with IC50 of 6 nM in cell-free assays, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε. Phase 3.

Size Price Stock Quantity  
10mM (1mL in DMSO) USD 109 In stock
USD 120 In stock
USD 370 In stock
USD 970 In stock
Bulk Discount
Bulk Inquiry

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Selleck's Enzastaurin (LY317615) has been cited by 36 publications

Purity & Quality Control

Choose Selective PKC Inhibitors

Biological Activity

Description Enzastaurin (LY317615) is a potent PKCβ selective inhibitor with IC50 of 6 nM in cell-free assays, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε. Phase 3.
Targets
PKCβ [1]
(Cell-free assay)		 PKCα [1]
(Cell-free assay)		 PKCγ [1]
(Cell-free assay)		 PKCε [1]
(Cell-free assay)
6 nM 39 nM 83 nM 110 nM
In vitro

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. [1] Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrated an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 led 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 induced the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. [2]
Assay
Methods Test Index PMID
Western blot
p27 / Cyclin D1 / Bcl-2 / Survivin ; 

PubMed: 22253748     


Cells were treated with enzastaurin for 72 hours and analyzed by immunoblot analysis. WT = GNAQ wild type; MT = GNAQ mutation.

p-ERK / ERK / p-AKT / AKT ; 

PubMed: 22253748     


Cells were treated with enzastaurin for 72 hours and analyzed for the expression of Akt and Erk1/2 and their phosphorylation by immunoblot analysis. WT = GNAQ wild type; MT = GNAQ mutation.

PKCα / PKCβ / PKCδ / PKCε / PKCθ / p-PKCε / p-PKCθ; 

PubMed: 22253748     


A and B, enzsaurin reduced the expression and phosphorylation of PKCβ, PKCε and PKCθ. Cells were treated with enzastaurin for 6 hours in the absence of serum (A) or for 72 hours in the presence of 10% FBS (B). pPKCε Thr566 was detected using pan p-PKC antibody raised against pPKCζ Thr410. Note that the expression of PKCβ was under detectable level of Western blot in Mel285 cells (B). 

p-eIF2a / eIF2a / p-ATF2 / ATF2 / CHOP / p21 / ATF6 / IRE1α ; 

PubMed: 19018094     


Protein profiling of MM cells exposed to enzastaurin. MM.1S cells were exposed to enzastaurin for increasing time periods followed by immunoblot analysis with the indicated antibodies. Tunicamycin (TM) was used as a positive control for ER stress signaling. 

22253748 19018094
Growth inhibition assay
Cell viability; 

PubMed: 22253748     


Enzastaurin exhibited greater antiproliferative effects on UM cell lines carrying GNAQ mutations (MT) than those with wild type GNAQ (WT). Cells were treated with varying amount of enzastaurin for 72 hours and subjected to MTS assay. Results are presented as mean ± SD of percent viability from three independent experiments.

22253748
In vivo Treatment of xenografts with Enzastaurin and radiation produced greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponded to delayed tumor growth. [3]

Protocol

Kinase Assay:

[1]
- Collapse

Kinase inhibition assays:

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.
Cell Research:

[1]
- Collapse
  • Cell lines: HCT116 and U87MG cells
  • Concentrations: 0.3-4 μM
  • Incubation Time: 72 hours
  • Method:

    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.


    (Only for Reference)
Animal Research:[1] [3]
- Collapse
  • Animal Models: Athymic nude mice; Mouse besring human MM tumors
  • Dosages: 75 mg/kg twice daily; 30 mg/kg twice daily
  • Administration: By gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 30 mg/mL (58.18 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
15% Captisol
For best results, use promptly after mixing. 		30 mg/mL

* 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 Information

Molecular Weight 515.61
Formula

C32H29N5O2
CAS No. 170364-57-5
Storage powder
in solvent
Synonyms N/A
Smiles CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CN(C5=CC=CC=C54)C6CCN(CC6)CC7=CC=CC=N7

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03263026 Recruiting Drug: Enzastaurin Hydrochloride|Other: R-CHOP + placebo Diffuse Large B-Cell Lymphoma Denovo Biopharma LLC March 20 2018 Phase 3
NCT01432951 Completed Drug: Enzastaurin Solid Tumor|Lymphoma Malignant Eli Lilly and Company November 2011 Phase 1
NCT01388335 Completed Drug: warfarin|Drug: enzastaurin Solid Tumor|Lymphoma Malignant Eli Lilly and Company August 2011 Phase 1
NCT00744991 Completed Drug: Enzastaurin Cutaneous T-Cell Lymphoma Eli Lilly and Company September 2008 Phase 2
NCT00709995 Completed Drug: Enzastaurin|Drug: Sunitinib|Drug: Placebo Metastatic Renal Cell Carcinoma Eli Lilly and Company June 30 2008 Phase 2

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.

Handling Instructions

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

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

  • * Indicates a Required Field
selleck catalog

PKC Signaling Pathway Map

PKC Inhibitors with Unique Features

  • Pan PKC Inhibitor

    Sotrastaurin : Pan-PKC inhibitor, PKCα, Ki=0.95 nM; PKCβ, Ki=0.64 nM; PKCδ, Ki=2.1 nM; PKCε, Ki=3.2 nM; PKCη, Ki=1.8 nM; PKCθ, Ki=0.22 nM.

  • Most Potent PKC Inhibitor

    Go 6983 : PKCα, IC50=7 nM; PKCβ, IC50=7 nM; PKCγ, IC50=6 nM; PKCδ, IC50=10 nM.

  • PKC Inhibitor in Clinical Trial

    Dequalinium Chloride : Phase III for Bacterial Vaginosis.

  • Newest PKC Inhibitor

    Ro 31-8220 Mesylate New : Pan-PKC inhibitor with IC50 of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, and PKC-ε, respectively, and also shows potent inhibition against MAPKAP-K1b, MSK1, GSK3β and S6K1.

Related PKC Products

  • SD-208 New

    SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.

  • LDN-214117 New

    LDN-214117 is a potent and selective BMP type I receptor kinase ALK2 inhibitor with IC50 of 24 nM.

  • Staurosporine

    Staurosporine (CGP 41251) is a potent PKC inhibitor for PKCα, PKCγ and PKCη with IC50 of 2 nM, 5 nM and 4 nM, less potent to PKCδ (20 nM), PKCε (73 nM) and little active to PKCζ (1086 nM) in cell-free assays. Also shows inhibitory activities on other kinases, such as PKA, PKG, S6K, CaMKII, etc. Phase 3.

  • Sotrastaurin

    Sotrastaurin (AEB071) 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.

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

  • Go 6983

    Go 6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ and PKCδ with IC50 of 7 nM, 7 nM, 6 nM and 10 nM, respectively; less potent to PKCζ and inactive to PKCμ.

  • Bisindolylmaleimide I (GF109203X)

    Bisindolylmaleimide I (GF109203X) is a potent PKC inhibitor with IC50 of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ in cell-free assays, respectively, showing more than 3000-fold selectivity for PKC as compared to EGFR, PDGFR and insulin receptor.

    Features:Greater selectivity than PKC inhibitor staurosporine. GF109203X is a chemical probe for studying PKC signal transduction pathways. Potential for use in a variety of cancers.

  • Go6976

    Go6976 is a potent PKC inhibitor with IC50 of 7.9 nM, 2.3 nM, and 6.2 nM for PKC (Rat brain), PKCα, and PKCβ1, respectively. Also a potent inhibitor of JAK2 and Flt3.

  • Bisindolylmaleimide IX (Ro 31-8220 Mesylate)

    Bisindolylmaleimide IX (Ro 31-8220 Mesylate) is a pan-PKC inhibitor with IC50 of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, and PKC-ε, respectively, and also shows potent inhibition against MAPKAP-K1b, MSK1, GSK3β and S6K1.

  • Dequalinium Chloride

    Dequalinium Chloride is a PKC inhibitor with IC50 of 7-18 μM, and also a selective blocker of apamin-sensitive K+ channels with IC50 of 1.1 μM.

Tags: buy Enzastaurin (LY317615) | Enzastaurin (LY317615) supplier | purchase Enzastaurin (LY317615) | Enzastaurin (LY317615) cost | Enzastaurin (LY317615) manufacturer | order Enzastaurin (LY317615) | Enzastaurin (LY317615) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID