Enzastaurin is a synthetic bisindolylmaleimide with potential antineoplastic activity. Binding to the ATP-binding site, enzastaurin selectively inhibits protein kinase C beta, an enzyme involved in the induction of vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis.
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Enzastaurin is a synthetic bisindolyl maleimide with potential antineoplastic activity. Binding to the ATP-binding site enzastaurin selectively inhibits protein kinase C beta, an enzyme involved in the induction of vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis. Inhibition at this level halts signals promoting survival and re-growth of damaged cells. This agent may decrease tumor blood supply, preventing growth. Enzastaurin has received a great deal of attention in recent times. Developed by Eli Lilly, enzastaurin is extensively listed in literature under the code names LY-317615 and D04014. Enzastaurin has demonstrated activity towards the PKC isoform with an enzastaurin IC50 of 6nM, relative to the IC50's for the α, ε and γ isoforms (39, 110 & 83 nM). Enzastaurin solubility in DMSO is limited compared to similar compounds achieving only a 7.1 mg /ml saturated solution after gentle warming. In ethanol and aqueous solutions the solubility is lower limiting buffer concentrations to 1 - 10 µM.
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Enzastaurin adds specificity at low concentrations toward the PKC ß isoforms with some activity towards the α, ε and γ isoforms. In addition, it has been established that Enzastaurin has activity towards GSK3 (also known as SER9) and towards the ribosomal protein S6 (also known as SER240/244). Against a panel of SCLC and nSCLC cell lines Enzastaurin demonstrated low µM sensitivity, inhibiting cell growth and exhibiting a decrease in GSK activity. In various animal models enzastaurin has demonstrated prolific anti tumor activity in a range of tumor types (renal, hepatic and colon). Synergistically enzastaurin has demonstrated good sensitivity in combination with tyrosine kinase inhibitors, platinum compounds and other first line traditional treatment profiles.
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Enzastaurin clinical trials are ongoing for a variety of conditions such Malignant Gliomas, refractory mantle cell lymphoma, tumors of the central nervous system, non Hodgkin's lymphomas, breast cancer and glioblastoma multiform to name only a few of the many avenues of investigation that are being pursued with this material. Enzastaurin specifications
- Product Number: E-2048. Available in 1mg and 5 mg catalog sizes. Contact us for other quantities, OEM packaging or bulk inquiries.
- CAS # 170364-57-5
- Chemical Formula: C32H29N5O2
- Appearance: Solid
- Molecular Weight: 515.61
- Purity: 99%
- Solubility: DMSO
- http://www.ncbi.nlm.nih.gov
- Br J Cancer. 2012 Feb 28;106(5):867-75. doi: 10.1038/bjc.2012.7. Epub 2012 Feb 14.
- Department of Internal Medicine, Division of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
- http://www.selleckchem.com
- Wikipedia
- http://jco.ascopubs.org/content/24/25/4092.full