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Cytostatic activity and selectivity of dipeptidyl nitrile derivatives with cysteine protease inhibition in pancreatic cancer cell line

Grant number: 18/09365-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2018
Effective date (End): July 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal researcher:Andrei Leitão
Grantee:Sabrina Mendes Botelho
Home Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil


Cysteine protease inhibitors have been described as cytostatic agents working as inhibitors of metastasis in many neoplasias, among them in pancreatic cancer cell lines. These cells overexpress cysteine proteases. In this Project, in vitro assays using the pancreatic cell line (MIA PaCa-2) and Balb/C 3T3 clone A31 mouse fibroblasts will be used to determine the selectivity profile for a set of compounds synthesized by the NEQUIMED group. Moreover, several assays like proteolytic activity in cells, clonogenic assay cell replication and wound healing will be applied to understand how these substances modulate the cell response. Therefore, the pharmacological profile for the dipeptidyl nitrile derivatives will be accessed to select the most promising compounds for the optimization of potency and pharmacokinetics/toxic properties.

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