CAS Number170364-57-5
Synonyms3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione; LY-317615; LY317615; Enzastaurin
Molecular FormulaC32H29N5O2
Molecular Weight515.60
Purity96+%
Density1.34
Boiling Point767.2±60.0 °C at 760 mmHg
Melting Point249-261℃
Appearancepowder,light orange to dark orange-red
EINECS0
Symbol
Signal WordWarning
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 170364-57-5 |
| Catalog No. | 2A-0126289 |
| Chinese Name | 恩扎妥林 |
| Synonyms | 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione; LY-317615; LY317615; Enzastaurin |
| Molecular Formula | C32H29N5O2 |
| Molecular Weight | 515.60 |
| Purity | 96+ |
| Density | 1.34 |
| Boiling Point | 767.2±60.0 °C at 760 mmHg |
| Melting Point | 249-261℃ |
| Appearance | powder,light orange to dark orange-red |
| Water Solubility | DMSO: soluble10mg/mL, clear (warmed) |
| Storage Condition | -20°C |
| Application | Enzastaurin is a potent inhibitor of PKCβ with an IC50 value of 6 nM; it is 6-20 times more selective than PKCα, PKCγ and PKCε. |
| EINECS | 0 |
| HTC | 2933990090 |
| UN(IATA) | 0 |
| PubChem ID | 10258360 |
| SMILES | Cn1cc(C2=C(c3cn(C4CCN(Cc5ccccn5)CC4)c4ccccc34)C(=O)NC2=O)c2ccccc21 |
| InChI | InChI=1S/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) |
| InChI Key | AXRCEOKUDYDWLF-UHFFFAOYSA-N |
| NACRES Code | NA.77 |
| UNSPSC | 12352200 |
| Hazard Symbols | transportation |
| Bioactivity | Enzastaurin is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε. Related Catalog Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Epigenetics >> PKC Signaling Pathways >> TGF-beta/Smad >> PKC Research Areas >> Cancer Target PKCβ:6 nM (IC50) PKCα:39 nM (IC50) PKCγ:83 nM (IC50) PKCε:110 nM (IC50) 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]. Kinase Assay 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 Assay 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. References [1]. Rovedo MA, et al. Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin. J Invest Dermatol, 2011, 131(7), 1442-1449. [2]. Podar K, et al. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl). Blood, 2007, 109(4), 1669-1677. [3]. Graff JR, et al. 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, 2005, 65(16), Chemical & Physical Properties Density 1.34 Boiling Point 767.2±60.0 °C at 760 mmHg Melting Point 249-261℃ Molecular Formula C32H29N5O2 Molecular Weight 515.605 Flash Point 417.8±32.9 °C Exact Mass 515.232117 PSA 72.16000 LogP 4.43 Appearance of Characters powder,light orange to dark orange-red Vapour Pressure 0.0±2.6 mmHg at 25°C Index of Refraction 1.723 InChIKey AXRCEOKUDYDWLF-UHFFFAOYSA-N SMILES Cn1cc(C2=C(c3cn(C4CCN(Cc5ccccn5)CC4)c4ccccc34)C(=O)NC2=O)c2ccccc21 Storage condition -20°C Water Solubility DMSO: soluble10mg/mL, clear (warmed) |
| Use of | Enzastaurin is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε. Properties Name 3-(1-Methyl-1H-indol-3-yl)-4-(1-(1-(pyridin-2-ylmethyl)piperidin-4-yl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione Synonym More Synonyms Enzastaurin (LY317615) Biological Activity Description Enzastaurin is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε. Related Catalog Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Epigenetics >> PKC Signaling Pathways >> TGF-beta/Smad >> PKC Research Areas >> Cancer PKCβ:6 nM (IC50) PKCα:39 nM (IC50) PKCγ:83 nM (IC50) PKCε:110 nM (IC50) 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]. References [1]. Rovedo MA, et al. Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin. J Invest Dermatol, 2011, 131(7), 1442-1449. [2]. Podar K, et al. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl). Blood, 2007, 109(4), 1669-1677. [3]. Graff JR, et al. 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, 2005, 65(16), Chemical & Physical Properties Molecular Formula C32H29N5O2 Exact Mass 515.232117 PSA 72.16000 Appearance of Characters powder,light orange to dark orange-red Index of Refraction 1.723 InChIKey AXRCEOKUDYDWLF-UHFFFAOYSA-N |
| Tax Rebate | 13.0% |
| Supervision | None. MFN tariff: 6.5%. Ordinary tariff: 20.0% |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.2 United Nations shipping name European Land Transport Dangerous Regulations: Non-dangerous goods IMDG Code: Non-dangerous goods International air transport dangerous goods regulations: non-dangerous goods 14.3 Transport hazard categories European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.4 Package group European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available |
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