AEterna Zentaris Presents Positive Preclinical Data in Breast Cancer on AEZS-131, a Highly Selective Erk 1/2 Inhibitor, at San Antonio Breast Cancer Symposium
Published: Dec 09, 2011
|Poster #P3-18-06:||"AEZS- 131 - a highly selective ERK-inhibitor: Characterization and preclinical testing in triple-negative breast cancer (TNBC)", Engel Jörg B., Seipelt Irene, Hönig Arnd, Hahne Jens C., Teifel Michael.|
AEZS-131 was tested to check for selectivity, inhibition of Rsk-phosphorylation (cellular substrate of Erk), mode of action and cleavage of PARP. Cytotoxic efficacy was evaluated in a selection of TNBC cell lines, with or without mutations in the MAPK signal transduction pathway, by MTT assay.
The study showed that AEZS-131 selectively inhibited ERK with an IC50<4nM. Phosphorylation of Rsk-1, the cellular substrate of Erk, was inhibited with an IC50 of 158 nM. AEZS-131 induced cell cycle arrest in G1 dose-dependently and cleavage of PARP. EC50 values were below 1µM for cell lines with mutations in the MAPK pathway. TNBC cell lines without mutations in the MAPK pathway were less responsive.
Dr. Jörg B. Engel, of the Medical University of Regensburg, commented, "Over-expression of MAPK has been detected in 34% of triple-negative breast cancer and has been found to be associated with an increased risk for recurrence in patients with this type of breast cancer. Since preclinical data suggest that AEZS-131's cytotoxic effect was most pronounced in triple-negative breast cancer cell lines with mutations in the MAPK pathway, we, therefore, believe this compound should be further explored in triple-negative breast cancer with over activation of MAPK or mutations in the MAPK-pathway."
The poster is available at the following link.
About Erk 1/2 Inhibitor Compound
Extracellular signal-regulated kinases ("Erks") act in the Ras-Raf-Mek-Erk signaling cascade and regulate various cellular processes such as cell growth, proliferation and survival in response to a variety of extracellular or intrinsically mutated upstream signals. Aeterna Zentaris has identified small molecular compounds that selectively inhibit Erk 1/2, among them AEZS-131, which has been shown to significantly inhibit tumor growth in in vivo studies. Early development of the Erk inhibitor AEZS-131 is an integral part of Aeterna Zentaris' kinase research program comprising the investigation of different compounds for single Erk inhibition, single PI3K inhibition and dual Erk/PI3K kinase inhibition.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development company currently investigating potential treatments for various cancers including colorectal, multiple myeloma, endometrial, ovarian, prostate and bladder cancer. The Company's innovative approach of "personalized medicine" means tailoring treatments to a patient's specific condition and to unmet medical needs. Aeterna Zentaris' deep pipeline is drawn from its proprietary discovery unit providing the Company with constant and long-term access to state-of-the-art therapeutic options. For more information please visit www.aezsinc.com
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