In Vitro and In Vivo Data Show AEZS-126 as Promising Oral Compound for
Future Clinical Development in Cancer
QUEBEC CITY, April 21 /CNW Telbec/ - AEterna Zentaris Inc. (TSX: AEZ;
NASDAQ: AEZS), a global biopharmaceutical company focused on endocrine therapy
and oncology, today presented two posters on AEZS-126, a promising compound
for clinical intervention of the PI3K/ Akt pathway in human tumors. The
posters were presented at the American Association for Cancer Research (AACR)
Annual Meeting in Denver, Colorado.
Entitled, "AEZS-126, a new orally bioavailable PI3K inhibitor with
antitumor effects", I. Seipelt, S. Baasner, M. Gerlach, M. Teifel, J.
Fensterle, L. Blumenstein, G. Mueller and E. Guenther, the poster focuses on
ADMET and safety profiling of the compound, as well as in vivo pharmacokinetic
experiments and mouse xenograft antitumor studies.
AEZS-126 was identified as a potent inhibitor of class I PI3Ks in
biochemical and cellular assays and demonstrated favorable properties in early
in vitro ADMET screening including microsomal stability, plasma stability and
screening against a large safety profile composed of receptors, enzymes and
cardiac ion-channels. During the course of in vivo pharmacokinetic experiments
and mouse xenograft antitumor studies, the oral bioavailability in mice was
determined to be about 60%, leading to micromolar plasma levels which are well
above the nanomolar IC50 values in in vitro studies. Significant antitumor
activity was observed at 30mg/kg daily oral administration in Hct116 and A549
These data suggest that AEZS-126 is a promising compound for clinical
intervention of the PI3K/Akt pathway in human tumors.
Entitled, "In vitro profiling of the potent and selective PI3K inhibitor,
AEZS-126", I. Seipelt, M. Gerlach, L. Blumenstein, G. Mueller, M.Teifel, E.
Polymeropoulos and E. Guenther, the poster outlines the key in vitro
characteristics of this compound that led to its selection for in vivo
AEterna Zentaris has identified a new generation of low molecular weight
pyridopyrazine compounds as highly potent and selective inhibitors of class I
PI3Ks. Presented here, are the key in vitro characteristics of AEZS-126 that
led to its selection for in vivo development. AEZS-126 inhibits PI3Ka with an
IC50 value of 10nM and proved to be a potent inhibitor of Akt phosphorylation
in cellular assays. Mode-of-action studies showed that AEZS-126 acts as an ATP
competitive compound. The in vitro antiproliferative activity against
different human tumor cell lines (MDA-MB 468, U87, Hct116, PC-3, A549 and
others) was determined, with EC50 values in the nanomolar range.
The optimization of AEterna Zentaris' pyridopyrazine lead structure
regarding kinase selectivity, cellular potency and ADMET properties, led to
the identification of AEZS-126, a compound which has a favorable in vitro
pharmacologic profile for further in vivo profiling.
About AEterna Zentaris Inc.
AEterna Zentaris Inc. is a global biopharmaceutical company focused on
endocrine therapy and oncology, with proven expertise in drug discovery,
development and commercialization. News releases and additional information
are available at www.aezsinc.com.
This press release contains forward-looking statements made pursuant to
the safe harbor provisions of the U.S. Securities Litigation Reform Act of
1995. Forward-looking statements involve known and unknown risks and
uncertainties, which could cause the Company's actual results to differ
materially from those in the forward-looking statements. Such risks and
uncertainties include, among others, the availability of funds and resources
to pursue R&D projects, the successful and timely completion of clinical
studies, the ability of the Company to take advantage of business
opportunities in the pharmaceutical industry, uncertainties related to the
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