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Enzastaurin (LY317615)

PKC beta inhibitor,potent and selective

Enzastaurin (LY317615)

Catalog No. A1670
Size Price Stock Qty
Evaluation Sample $28.00 In stock
5mg $50.00 In stock
25mg $120.00 In stock
100mg $360.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

Enzastaurin (LY317615)

Related Biological Data

Enzastaurin (LY317615)

Related Biological Data

Enzastaurin (LY317615)

Biological Activity

Description Enzastaurin (LY317615) is a potent and selective inhibitor of PKCβ with IC50 of 6 nM.
Targets PKCβ PKCα PKCγ PKCε    
IC50 6 nM 39 nM 83 nM 110 nM    

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Chemical Properties

Cas No. 170364-57-5 SDF Download SDF
Chemical Name 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione
Canonical 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
Formula C32H29N5O2 M.Wt 515.61
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. A randomized, double-blind, placebo-controlled, Phase II study with and without enzastaurin in combination with docetaxel-based chemotherapy in patients with castration-resistant metastatic prostate cancer. Invest New Drugs. 2013 Aug;31(4):1044-50. doi: 10.1007/s10637-013-9940-0. Epub 2013 Feb 24.
Abstract
The efficacy of docetaxel/prednisone with or without enzastaurin, an inhibitor of the beta isoform of protein kinase C with therapeutic activity against prostate cancer, in patients with castration-resistant metastatic prostate cancer has been explored.
2. The serine-threonine kinase p90RSK is a new target of enzastaurin in follicular lymphoma cells. Br J Pharmacol. 2013 Dec;170(7):1374-83. doi: 10.1111/bph.12351.
Abstract
Follicular lymphoma cells are characterized not only by genetic alterations involving Bcl-2, Bcl-6 OR C-mYc but also by alterations in B-cell receptor signaling pathways.
4. Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics. Invest New Drugs. 2013 Jun;31(3):653-60. doi: 10.1007/s10637-012-9850-6. Epub 2012 Jul 6.
Abstract
The combination of enzastaurin and bevacizumab, which showed synergistic antitumor activity in preclinical studies, was evaluated for safety and efficacy.
5. A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer. Cancer. 2012 Sep 1;118(17):4132-8. doi: 10.1002/cncr.26692. Epub 2011 Dec 27.
Abstract
Enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab was evaluated as maintance therapy for MCRC, since the combination of enzastaurin and bevacizumab was well-tolerated and demonstrated synergistic antitumor effects in phse 1 studies.

Background

Enzastaurin is an ATP-competitive, selective oral inhibitor of protein kinase Cβ with IC50 value of 6 nM [1].
Protein kinase C (PKC) is a family of serine-threonine protein kinases that have been proved to play critical roles in the formation and progression of tumor cells. The PKCβ is especially found to contribute to the growth and proliferation of tumors such as diffuse large B-cell lymphoma, multiple myeloma and chronic lymphoid leukemia. The selective PKCβ inhibitor enzastaurin was found to have antiangiogenic activity in tumor model as well as suppress tumor proliferation and induce apoptosis. Besides that, enzastaurin showed the inhibitory effects on phosphorylation of ribosomal protein S6, GSK3β and AKT which are in pathways influenced by PKC. Due to these, enzastaurin was developed as a therapy for cancer [1 and 2].
Enzastaurin at low concentration suppressed cell proliferation of various tumor cells including colon carcinoma (HCT-116), glioblastoma (U87MG), non–small cell lung cancer (A549), melanoma (M14), ovarian cancer (OVCAR-3), breast cancer (MCF-7), leukemia (K562), prostate cancer (PC-3), renal cancer (CAKI-1) and central nervous system cancer (U251). Enzastaurin induced apoptosis of tumor cells at low concentration in a range of 1 to 4 μM and the apoptosis was proved to be caspase-independent. In addition, enzastaurin suppressed the phosphorylation ofGSK3βSer9, ribosomal protein S6Ser240/244 and AKTThr308 time-dependently in tumor cells and affected these pathways [1 and 3].
In mice models, oral administration of enzastaurin at a dose of 75 mg/kg resulted in significant proliferation inhibition of U87MG glioblastoma or HCT116 coloncarcinoma xenografts. In mice bearing human walden strommacro globulinemia xenografts, administration of enzastaurin at dose of 80 mg/kg significantly reduced tumor growth of WM and increased survival [1 and 2].
References:
[1] Graff J R, McNulty A M, Hanna K R, et al. The protein kinase Cβ–selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Research, 2005, 65(16): 7462-7469.
[2] Moreau A S, Jia X, Ngo H T, et al. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenströmmacroglobulinemia. Blood, 2007, 109(11): 4964-4972.
[3] Rizvi M A, Ghias K, Davies K M, et al. Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. Molecular cancer therapeutics, 2006, 5(7): 1783-1789.