Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity

• Main Authors: Durvanei A. Maria, Sonia Elisabete A.L. Will, Rosemary V. Bosch, Jean G. Souza, Juliana M. Sciani, Mauricio B. Goldfeder, Giuliana G. Rondon, Ana M. Chudzinski-Tavassi
• Format: Article
• Language: English
• Published: Elsevier 2019-01-01
• Series: Toxicology Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214750018305468

Amblyomin-X, a Kunitz-type protease inhibitor, is a recombinant protein that selectively induces apoptosis in tumor cells and promotes tumor reduction in vivo in melanoma animal models. Furthermore, Amblyomin-X was able to drastically reduce lung metastasis in a mice orthotopic kidney tumor model. Due to its antitumor activity, Amblyomin-X potential to become a new drug is currently under investigation, therefore the aim of the present study was to perform preclinical assays to evaluate Amblyomin-X toxicity in healthy mice. Exploratory toxicity assays have shown that treatment with 512 mg/kg of Amblyomin-X lead to animal mortality, therefore two groups of treatment were evaluated in the present work: in the acute toxicity assay, animals were injected once with doses ranging from 4 to 256 mg/kg of Amblyomin-X, while in the subacute toxicity assay, animals were injected with 0.25, 0.57 and 1 mg/kg of Amblyomin-X daily, during 28 days. Following this treatment regimens, Amblyomin-X did not cause any mortality; moreover, toxicity signs were discrete, reversible and observed only at the higher doses, thus establishing a safety profile for administration in mice, which can be further used to determine the dose translation of this novel drug candidate for treatment in other species. Keywords: Amblyomin-X, Kunitz-type inhibitor, Toxicity, Preclinical