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


Publication type
Article
Language
English
Access rights
Open Access
Appears in Collections:
Metrics
Abstract
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.
Reference
Maria DA, Will SEAL, Bosch RV, Souza JG, Sciani JM, Goldfeder MB, et al. Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity. Toxicol. Rep.. 2019;6:51-63. doi:10.1016/j.toxrep.2018.11.014.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/2630
Journal title
Issue Date
2019


Files in This Item:

10.1016j.toxrep.2018.11.014.pdf
Size: 8.21 MB
Format: Adobe PDF
View/Open
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.