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BMS-536924, an ATP-competitive IGF-1R/IR Inhibitor, Decreases Viability and Migration of Temozolomide-Resistant Glioma Cells in Vitro and Suppresses Tumor Growth in Vivo

BMS-536924, an ATP-competitive IGF-1R/IR Inhibitor, Decreases Viability and Migration of Temozolomide-Resistant Glioma Cells in Vitro and Suppresses Tumor Growth in Vivo

Qiao Zhou

Onco Targets Ther. 2015 Apr 2;8:689-97.

PMID: 25897243

Abstract:

Glioma is the most common type of primary brain tumor. Despite the combination of surgery, chemotherapy, and radiotherapy, the median survival duration of patients with malignant glioma is still very short. Temozolomide (TMZ) is the primary and most promising therapeutic drug for glioma; however, it is easy to develop acquired resistance during treatment. Activation of receptor tyrosine kinases (RTKs) has been identified to be involved in the acquisition of resistance toward many anticancer drugs. So inhibition of RTKs might be a promising therapeutic strategy for overcoming or attenuating acquired drug resistance. Here, we have investigated the anticancer activities of BMS-536924, an ATP-competitive IGF-1R/IR inhibitor in glioma, especially TMZ-resistant glioma, both in vitro and in vivo. We found that BMS-536924 could effectively reduce viability of both TMZ-sensitive and -resistant glioma cells. BMS-536924 induced dramatic apoptosis in TMZ-resistant cells, and it also dramatically inhibited migration of TMZ-resistant cells. Importantly, BMS-536924 significantly suppressed glioma tumor growth in vivo. This is the first report on anticancer activity of BMS-536924 in glioma. BMS-536924 is a promising compound in the therapy of glioma, especially of TMZ-resistant glioma, which might shed new light on glioma therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP468740434	BMS-536924		468740-43-4	Price

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