EntreMed (ENMD) Said ENMD-2076 Demonstrates Antitumor Activity
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EntreMed, Inc. (Nasdaq: ENMD) announced the presentation of preclinical data for its Aurora A/angiogenesis kinase inhibitor, ENMD-981693, the free base of ENMD-2076.
ENMD-2076 free base exhibited dose-dependent cytotoxicity towards multiple myeloma (MM) cell lines, and was shown to induce cell death in vitro following relatively short (6 hour) exposures through apoptosis via a mitochondrial pathway. Consistent with the effect of ENMD-2076 free base on several receptor tyrosine kinases, inhibition of phosphorylation of proteins in the oncogenic PI3-kinase/Akt pathway including p-BAD, p-FOXO1a, and p-GSK3beta was observed. Longer incubations of MM cells (24-48 hours) with ENMD-2076 free base elicited increased cell death with concomitant inhibition of Aurora A autophosphorylation, induction of cell cycle arrest, and downregulation of cyclins A and B1. ENMD-2076, administered either on a daily or weekly schedule, elicited complete inhibition of tumor growth towards a xenograft of the human myeloma cell line H929 in vivo.
ENMD-2076 free base exhibited dose-dependent cytotoxicity towards multiple myeloma (MM) cell lines, and was shown to induce cell death in vitro following relatively short (6 hour) exposures through apoptosis via a mitochondrial pathway. Consistent with the effect of ENMD-2076 free base on several receptor tyrosine kinases, inhibition of phosphorylation of proteins in the oncogenic PI3-kinase/Akt pathway including p-BAD, p-FOXO1a, and p-GSK3beta was observed. Longer incubations of MM cells (24-48 hours) with ENMD-2076 free base elicited increased cell death with concomitant inhibition of Aurora A autophosphorylation, induction of cell cycle arrest, and downregulation of cyclins A and B1. ENMD-2076, administered either on a daily or weekly schedule, elicited complete inhibition of tumor growth towards a xenograft of the human myeloma cell line H929 in vivo.
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