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IC50: The value varied among different tumor type. In Saos-2-His-273 cells, PRIMA-1 induced cell death with an IC50 of over 15 M.

PRIMA-1, a novel low molecular weight compound, rescues the tumor-suppressing function of mutant p53 proteins and shows anti-tumor activity in vivo. P53 severs as a crucial tumor suppressor and mutant p53 is expressed at high levels in many tumors. PRIMA-1 is considered as a lead compound for the development of anticancer drugs targeting mutant p53. [1]

In vitro: The substantial increase in Saos-2-His-273-cells death could be noticed after being treated with 125 μM PRIMA-1 for 48 hours. TUNEL staining revealed that such tumor-cell death was primarily triggered by apoptosis. PRIMA-1 could also restore the transcriptional transactivation function to mutant p53 in vitro. [2]

In vivo: To assess the effect of PRIMA-1 on human tumor xenografts, mice were inoculated with Saos-2-His-273 cells expressing mutant p53. The mice then received PRIMA-1 treatment at intra-tumor does of 20 mg/kg or i.v. doses of 20 and 100 mg/kg twice a day for three days. Compared with the control group, the average tumor volume decreased from 555.7 mm3 to 11.7 (100 mg/kg) and 53 (20 mg/kg) mm3 after i.v. injections of PRIMA-1. Intra-tumor injections of PRIMA-1 also decreased the average tumor volume to 5.3 mm3. [2]

Clinical trial: The methylated form of PRIMA-1, PRIMA-1MET was tested on 22 patients with hematologic malignancies and prostate cancer. Based on the clinical data, PRIMA-1MET was safe at predicted therapeutic dose, had a favorable pharmacokinetic profile and could lead to apoptosis of tumor cells in the p53–dependent manner. [3]

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