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NSC319726

CAS No. : 71555-25-4

MCE 站：NSC319726

产品活性：NSC319726 (ZMC1) 是突变型p53R175再活化剂，能抑制表达p53R175的成纤维细胞增殖，IC50值为8nM，对野生型p53细胞无抑制作用。

研究领域：Apoptosis

作用靶点：MDM-2/p53

In Vitro: For NSC319726, the effect was even greater as the IC50 for the 175 mutant was 8 nM while the IC50 of the WT was not reached. NSC319726 did not induce WT p53 protein levels or transcriptional activity as common cytotoxic agents such as etoposide do in vitro. NSC319726 exhibited a much higher sensitivity for the MEF-p53R172H/R172H cell line as compared to the p53+/+ ａnd p53-/- controls. NSC319726 treatment of a MEF cell line derived from p53R172H/R172H mice resulted in a loss of PAB240 immunoflouresence staining.

In Vivo: At a dose of 1mg/kg, tumor growth of the H460 (p53+/+) ａnd MDAMB468 (p53R273W) xenografts was not inhibited relative to the vehicle control whereas tumor growth was significantly inhibited in the TOV112D (p53R175H) xenografts. When we lowered the dose ten-fold to 0.1 mg/kg in the TOV112D mice, we observed only a small difference in tumor growth inhibition demonstrating both a dosage effect of the drug ａnd a larger therapeutic window.Taken together, these findings provide in vivo evidence for allele specific p53 mutant reactivation.

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