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RTI.2015 - Colchicine derivatives as antineoplasic agents: patent filling (2015-2016)

Grant number: 15/14164-0
Support Opportunities:Research Grants - Technical Reserve for Institutional Research Infrastructure
Start date: September 01, 2015
End date: August 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:José Andrés Yunes
Grantee:José Andrés Yunes
Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Cellular microtubules are anticancer targets extensively validated in the clinic. Anti-tubulin agents that interact with the colchicine binding site are attracting a lot of interest for development of new drugs against cancer. We have designed, synthesized and tested a series of colchicine analogues and assessed their potential as anti-cancer agents. Compounds obtained showed in vitro anti-leukemic effects at the nanomolar concentration range, strongly blocked cell cycle progression in G2/M and induced cell death through apoptosis. a single weekly i.p. dose of 1 mg/kg of one colchicine analogue significantly slowed the progression of primary human Acute Lymphoblastic Leukemia (ALL) in NOD/Scid mice, the effect being comparable to that obtained with vincristine, as evaluated by the enumeration of ALL cells in the peripheral blood, bone marrow, spleen and liver. No toxicity was recorded. Animals treated one month with the colchicine analogue survived significantly longer than control: 69 days versus 36 days, at the higher dose given (0.5mg/kg/3x per week). These data were recently published in the European Journal of Medicinal Chemistry (doi: 10.1016 / j.ejmech.2015.02.041) and a Brazilian patent was filled in 25/11/2011 . Our institution has no Agency for Innovation, hence the need to hire third-party service for the international registration of our patent. The PCT (Patent Cooperation Treaty) and most of the expenses for the international filing of the patent in question were paid with funds from RTI years 2010 and 2013. It remains to be pay approximately R$ 9,000.00 for the Chinese and Canadian patent registration, plus future expenses, difficult to estimate at this moment, which will be necessary to formalize our responses to possible questions arising from the analysis stage of our patent application. Efforts are being made to the exploitation of this patent in conjunction with the Cristália company . (AU)

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