Aeterna Zentaris (AEZS) Reports Positive Preclinical Data for Erk 1/2 Inhibitor, AEZS-131
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Aeterna Zentaris Inc. (Nasdaq: AEZS) has announced positive preclinical data in triple-negative breast cancer (TNBC) for its highly selective Erk 1/2 inhibitor anticancer compound, AEZS-131. Data showed that AEZS-131 selectively inhibits Erk at low nanomolar (nM) concentrations and induces G1 arrest. Accordingly, the cytotoxic effect of AEZS-131 was most pronounced in TNBC cell lines with mutations in the MAPK pathway. Data were presented yesterday by Dr. Jorg B. Engel, Medical University of Regensburg, Department of Gynaecology and Obstetrics, Germany, during a poster session at the CTRC - AACR San Antonio Breast Cancer Symposium, in San Antonio, Texas.
The Study
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.
Results
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 1M for cell lines with mutations in the MAPK pathway. TNBC cell lines without mutations in the MAPK pathway were less responsive.
Dr. Jorg 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 Study
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.
Results
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 1M for cell lines with mutations in the MAPK pathway. TNBC cell lines without mutations in the MAPK pathway were less responsive.
Dr. Jorg 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."
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