Study of antitumor effectiveness of Ras GTPase peptide inhibitor (Inh-Ras) in xenograft model of non-small cell lung cancer

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Abstract

In recent years, treatment of tumors associated with the RAS oncogene has become an important problem. High level of mutations in this gene is characteristic of tumors of various locations which makes it an attractive target. Modern drugs selectively inhibiting mutant KRAS have significant benefits compared to traditional treatment methods but also have shortcomings including high rate of adverse events. Therefore, development of new drugs – Ras GTPase inhibitors – with better pharmacodynamics characteristics is an important task.
Aim. To study in vivo specific pharmacological activity of a new peptide inhibitor of Ras GTPase (Inh-Ras) in a xenograft model of human non-small cell lung cancer.
Statistically significant data on increased lifespan of mice who were administered Ras GTPase inhibitor compared to the control group were obtained: by 16 % for dose 5 mg/kg and by 36.3 % for dose 10 mg/kg. Additionally, dose-dependent slowing of tumor growth by 30.5 and 57.3 %, respectively, was observed. High specificity due to the mechanism of action of the peptide construct allows to anticipate minimization of side effects of the potential drug Inh-Ras.

About the authors

T. M. Kulinich

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Author for correspondence.
Email: sobral@mail.ru
ORCID iD: 0000-0003-2331-5753

 Tatiana Mikhailovna Kulinich 

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

E. A. Kudinova

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-5530-0591

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

A. V. Ivanov

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-6660-5895

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

A. M. Shishkin

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-4492-9543

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

V. V. Kaminsky

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

O. B. Knyazeva

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-8382-3579

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

I. A. Puchkov

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0009-0001-6651-8975

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

V. K. Bozhenko

Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-8351-8152

 86 Profsoyuznaya St., Moscow 117997, Russia 

Russian Federation

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