Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that a poster on its novel orally active anticancer Erk inhibitor, which includes AEZS-131, was presented at the 242nd American Chemical Society National Meeting held at the Colorado Convention Center in Denver, Colorado. The poster was presented by Matthias Gerlach, Ph.D., Senior Director of Medicinal Chemistry for Aeterna Zentaris Inc.
Focus on inhibition of downstream kinase Erk 1/2 activity as a therapeutic target is attractive because the pharmacologic inhibition of Erk 1/2 reverses the activation of the Ras-Raf-Mek-Erk signal transduction pathway through many common deregulated molecular lesions in cancer. This pathway controls a number of fundamental cellular processes including cell survival, proliferation, motility and differentiation. It is constitutively activated in cancers of the lung, colon, pancreas, kidney, and ovary. Erk is pivotal in the pathway downstream of Ras, Raf and Mek, acting as central point where multiple signaling pathways coalesce to drive transcription.
Entitled, "Novel Pyrido[2,3-b]pyrazines as orally active ERK inhibitors," M. Gerlach, I. Seipelt, G. Mueller, T. Schuster, L. Blumenstein, B. Aicher, E. Guenther and M. Teifel.
AEZS-131 is an orally active small molecular compound that selectively inhibits Erk 1/2 with an IC50 of 4nM. The in vitro antiproliferative efficacy proved to be excellent in diverse human tumor cell lines. GI50 values in the low nanomolar range were obtained. In vivo anti-tumor activity was studied in a mouse xenograft experiment utilizing the human HCT-116 colon cancer model. Up to 74% inhibition of tumor growth was achieved with daily oral doses of 30 - 120 mg/kg. Our medicinal chemistry programs are supported by X-ray crystallography and modeling towards the optimization of pyrido[2,3-b]pyrazines as novel series of kinase inhibitors.
Juergen Engel, Ph.D., Aeterna Zentaris' President and Chief Executive Officer, commented: "As part of our targeting strategy in cancer with perifosine, AEZS-108, AEZS-112 and AEZS-120, we are proud to have identified the first in class Erk 1/2 inhibitor with in vivo anticancer activity. In parallel we are also developing AEZS-129 a pan PI3K inhibitor without m-TOR activity as well as AEZS-132, a dual inhibitor of PI3K and Erk."