Molecular and Cellular Endocrinology 2014-08-05

CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo.

Alessandro Antonelli, Guido Bocci, Concettina La Motta, Silvia Martina Ferrari, Poupak Fallahi, Alda Corrado, Anna Fioravanti, Stefania Sartini, Paola Orlandi, Simona Piaggi, Alessandro Corti, Gabriele Materazzi, David Galleri, Salvatore Ulisse, Gabriella Fontanini, Romano Danesi, Federico Da Settimo, Paolo Miccoli

文献索引：Mol. Cell. Endocrinol. 393(1-2) , 56-64, (2014)

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摘要

CLM29 (a pyrazolo[3,4-d]pyrimidine, that inhibits RET, epidermal growth factor receptor, vascular endothelial growth factor receptor, and has an anti-angiogenic activity) has anti-neoplastic activity in papillary dedifferentiated thyroid cancer. Here we tested CLM29 in medullary thyroid cancer (MTC), in primary MTC cells (P-MTC) obtained at surgery, and in TT cells harboring (C634W) RET mutation. CLM29 (10, 30, 50 μM) inhibited significantly (P<0.001) the proliferation, and increased the percentage of apoptotic P-MTC, TT and human dermal microvascular endothelial cells. The inhibition of proliferation by CLM29 was similar in P-MTC cells with/without RET mutation. TT cells were injected sc in CD nu/nu mice, and tumor masses became detectable between 20 and 30 days after xenotransplantation; CLM29 (50mg/kg/die) reduced significantly tumor growth and weight, and microvessel density. The anti-tumor activity of CLM29 has been shown in MTC in vitro, and in vivo, opening the way to a future clinical evaluation.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.