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Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor, against non-small cell lung câncer

Grant number: 14/24455-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2015
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Pharmacology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Emer Suavinho Ferro
Grantee:Sarah Fernandes Teixeira
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Lung cancer is one of the most incident and lethal cancers in Brazil and all over the world, thus, the pursuit for new drugs to control this disease is necessary. Among the tumor cellular changes there are the high proliferative activity level and the consequent cellular membrane continuous and increased genesis. Consistently, certain phospholipids, such as miltefosine, that can disrupt the turnover of membranes, have antitumor activity. In the regard of the dependence of some specifics enzymes for the synthesis of membrane phospholipids, its inhibition constitutes an alternative of reduction of tumor development. Among the enzymes related to phospholipids turnover, there is the CTP: phosphoethanolamine cytidylyltransferase, which is usually overexpressed in tumor cells, included in lung cancer. Therefore, the therapeutic effect against cancer by pharmacological inhibition is expected. This study aim to evaluate the antineoplastic effects of CHY-1, a miltefosine analogue and potencial inhibitor of CTP: phosphoethanolamine cytidylyltransferase enzyme against non-small cell lung cancer. The analysis will be done by in vitro e in vivo assays, evaluating the activity over tumor cells and the immune system cells, and the response of these in the tumor. Others possible mechanisms will also be investigated. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEIXEIRA, SARAH FERNANDES; DE AZEVEDO, RICARDO ALEXANDRE; SILVA, ARTHUR CARVALHO; BRAGA, RODOLPHO CAMPOS; JORGE, SALOMAO DORIA; MARZAGAO BARBUTO, JOSE ALEXANDRE; ANDRADE, CAROLINA HORTA; FERREIRA, ADILSON KLEBER. Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells. BIOMEDICINE & PHARMACOTHERAPY, v. 84, p. 1019-1028, . (16/05351-4, 09/54599-5, 13/05396-0, 15/18528-7, 14/07341-0, 14/24455-0, 13/07273-2, 14/14267-1)
TEIXEIRA, SARAH F.; RODRIGUES, CECILIA P.; COSTA, CICERO J. S.; PETTINATI, THAIS N.; DE AZEVEDO, RICARDO A.; MAMBELLI, I, LISLEY; JORGE, SALOMAO D.; RAMOS, RODRIGO N.; FERRO, EMER S.; BARBUTO, JOSE A. M.; et al. Edelfosine: An Antitumor Drug Prototype. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 18, n. 6, p. 865-874, . (15/18528-7, 16/07519-0, 14/24455-0, 16/09392-7, 13/07273-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TEIXEIRA, Sarah Fernandes. Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor against non-small cell lung cancer.. 2016. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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