Details
Stereochemistry | ACHIRAL |
Molecular Formula | C32H29N5O2.ClH.H2O |
Molecular Weight | 570.081 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.Cl.CN1C=C(C2=C1C=CC=C2)C3=C(C(=O)NC3=O)C4=CN(C5CCN(CC6=CC=CC=N6)CC5)C7=CC=CC=C47
InChI
InChIKey=NCSOZDYVYDZHMT-UHFFFAOYSA-N
InChI=1S/C32H29N5O2.ClH.H2O/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);1H;1H2
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | H2O |
Molecular Weight | 18.0153 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C32H29N5O2 |
Molecular Weight | 515.605 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.
Originator
Sources: http://adisinsight.springer.com/drugs/800015989
Curator's Comment: # Eli Lilly
Approval Year
PubMed
Title | Date | PubMed |
---|---|---|
Enzastaurin and pemetrexed exert synergistic antitumor activity in thyroid cancer cell lines in vitro. | 2005 Dec |
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Enzastaurin, a protein kinase Cbeta- selective inhibitor, and its potential application as an anticancer agent in lung cancer. | 2007 Aug 1 |
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Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. | 2007 May 1 |
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The oral protein-kinase C beta inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines. | 2008 Jul |
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Sequence-dependent, synergistic antiproliferative and proapoptotic effects of the combination of cytotoxic drugs and enzastaurin, a protein kinase Cbeta inhibitor, in non-small cell lung cancer cells. | 2008 Jun |
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Enzastaurin. | 2008 Jun |
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Enzastaurin renders MCF-7 breast cancer cells sensitive to radiation through reversal of radiation-induced activation of protein kinase C. | 2008 Jun |
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Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer. | 2008 Mar 1 |
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Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric cancer cells. | 2008 Mar 15 |
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Protein kinase C beta in malignant pleural mesothelioma. | 2008 Oct |
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Waldenstrom macroglobulinemia. | 2008 Oct 18 |
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Molecular pathways involved in the synergistic interaction of the PKC beta inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cells. | 2008 Sep 2 |
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In Vivo Measurements of Tumor Metabolism and Growth after Administration of Enzastaurin Using Small Animal FDG Positron Emission Tomography. | 2009 |
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Design of Phase II cancer trials for evaluation of cytostatic/cytotoxic agents. | 2009 |
|
Synergistic anti-tumor efficacy of lovastatin and protein kinase C-beta inhibitor in hepatocellular carcinoma. | 2009 Aug |
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Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling. | 2009 Feb 12 |
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Protein kinase Cbeta is an effective target for chemoprevention of colon cancer. | 2009 Feb 15 |
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Synergistic effect of Sorafenib and Sunitinib with Enzastaurin, a selective protein kinase C inhibitor in renal cell carcinoma cell lines. | 2009 May 18 |
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Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. | 2009 May 28 |
|
Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer. | 2010 Mar |
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Long-term follow-up of chemonaive patients with asymptomatic metastatic colorectal cancer treated with enzastaurin in a window of opportunity phase II study. | 2010 May |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00332202
1125 mg loading dose then 500 mg, oral, daily, until disease progression or maximum of 3 years
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21606156
In the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 uM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin.
Substance Class |
Chemical
Created
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admin
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Edited
Sat Dec 16 10:09:42 UTC 2023
by
admin
on
Sat Dec 16 10:09:42 UTC 2023
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Record UNII |
7P5KLU0N3Q
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Record Status |
Validated (UNII)
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Record Version |
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7P5KLU0N3Q
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647031-15-0
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86278309
Created by
admin on Sat Dec 16 10:09:42 UTC 2023 , Edited by admin on Sat Dec 16 10:09:42 UTC 2023
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ANHYDROUS->SOLVATE |
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ACTIVE MOIETY |