【摘 要】
：
Neovascularization is critical to tumour growth and metastasis and this has led to the development of a number of marketed anti-angiogenic agents which target VEGF/VEGFR2 receptors, for clinical use i
【机 构】
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Almac Discovery, Seagoe Industrial Estate, Craigavon, Northern Ireland, UK
【出 处】
：
BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会)
论文部分内容阅读
Neovascularization is critical to tumour growth and metastasis and this has led to the development of a number of marketed anti-angiogenic agents which target VEGF/VEGFR2 receptors, for clinical use in specific types of cancer.However, incomplete responses and/or resistance to these therapies has highlighted the need for new agents targeting alternative pathways.Here we describe the characterisation of a novel peptide (ALM-201) derived from the natural protein FKBP-like binding protein (FKBPL), which has extremely potent anti-angiogenic activity, is highly effective in mouse xenograft models at low doses, and exerts its effects through binding to microtubules, using CD44 as a cellentry mechanism.ALM-201 has been profiled in a range of human microvascular endothelial cell (HMEC-1) assays and is an extremely potent inhibitor of migration, tubule formation and microvessel formation in vitro and in vivo.Although the peptide has a marked effect on migration, ALM-201 does not inhibit cellular proliferation in a range of growth factor stimulated proliferation assays.Importantly, and unusually for a peptide, ALM-201 has a pharmacokinetic/pharmacodynamic profile which allows for ≤q.d.dosing in mouse xenograft models.The peptide is well tolerated, with no signs of toxicity observed in mouse xenograft models up to 80 days of dosing.In summary, ALM-201 is a novel, targeted microtubule binding agent which exhibits potent anti-angiogenic activity in vitro and in vivo.Pre-clinical development is in progress, with a Phase 1 clinical study planned for 2012.
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