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news.Clinical-stage pharmaceutical company EntreMed has presented positive preclinical results for two of its clinical stage compounds, MKC-1 and ENMD-1198.
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MKC-1 administered in combination with paclitaxel in a preclinical, orthotopic breast tumor model demonstrated synergistic tumor inhibition. The combination of MKC-1 and paclitaxel, but neither agent alone, demonstrated tumor regression of the bulky breast cell line tumors grown in this model. In addition, the combination decreased angiogenesis and proliferation, and increased apoptosis as early as four days post treatment.
EntreMed also reported that treatment of the 1A9 human ovarian carcinoma cell line with ENMD-1198 induced cell cycle arrest and decreased levels of the oncogenic transcription factor proteins HIF-1alpha, pSTAT3, and pNFkappaB. Treatment with ENMD-1198 also downregulates expression of several tubulin isotypes in 1A9 cells, but not in ENMD-1198-resistant (1A9-1198R) cells. This, combined with the relative lack of inhibition of oncogenic proteins observed in 1A9-1198R cells, suggests interaction with tubulin may be important for the modulation of oncogenic proteins by ENMD-1198.
Mark Bray, vice president, research, at EntreMed, said: “Development of MKC-1 and ENMD-1198 is in line with the company’s focus on orally available, small molecule drugs for the treatment of cancer and inflammatory diseases.”