Antitumor effect of a new human epidermal growth factor receptor inhibitor

Abstract

Purpose of the study. Preclinical study in experiment of antitumor efficacy of a new substance synthesized on the basis of pyrimidin-4-one derivative.Materials and methods. The sodium salt of 4-{2-[2-[2-(4-hydroxy-3-methoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidin-1-yl}-benzsulfamide, a new inhibitor of the internal domain of the epidermal growth factor receptor (EGFR), was used in this study. All C57BL6 mice of both sexes were subcutaneously transplanted with B16/F10 melanoma. Twenty-four hours after tumor transplantation, mice in the main group (n = 18) were injected with a new EGFR inhibitor intramuscularly at a dose of 0.375 mg per mouse (15,0 mg/kg animal masses), while mice in the control group (n = 18) were injected with saline for injection. In both groups administration was carried out before natural death of animals according to the scheme: administration daily for 5 days, followed by 2 days of break. The dynamics of animal weight, dynamics of tumor node volume were evaluated, the tumor growth inhibition index (TGII) was calculated.Results. Tumor visualization time and animal weight did not statistically significantly differ between the groups during the whole study. In the main group there was a longer lifespan by 1.5 times on average (p ≤ 0.05), and smaller average tumor volume (by 19.2 times on 14 days in males, by 4.3 times in females, by 4.3 times on 28 days in males, by 2.5 times in females, p ≤ 0.05) than in the control group. At the same time, in the main group the tumor volume was smaller in males by 2.7 and 1.8 times (p ≤ 0.05), respectively on days 25 and 28 than in females. TGII in mice of both sexes was maximal on the 14th day with subsequent decrease by 40.3 % in females and only by 18.6 % in males, and during the whole experiment TGII in males was higher.Conclusion. The results showed inhibition of melanoma growth and increased lifespan of mice of both sexes (more pronounced in males) in the group with administration of a new EGFR inhibitor. This indicates the promising potential of this compound and the need to continue its preclinical study in other tumor models.

Keywords

• novel pyrimidin-4-one derivative-based egfr inhibitor
• b16/f10 melanoma
• c57bl6 mice
• tumor growth inhibition index
• sex-specific antitumor efficacy
• preclinical studies