Fundacao Butantan

Denise Vilarinho Tambourgi

Ogari De Castro Pacheco

Giselle Pidde Queiroz

Fábio Carlos Magnoli

Priscila Hess Lopes

Mario Tyago Murakami

Osvaldo Augusto Brazil Esteves Sant'Anna

Fernanda Calheta Vieira Portaro

This invention refers to polynucleotides and non-hemorrhagic and non-immunogenic polypeptides of selective immunosuppressive activity on production of antibodies to antigens of different natures. The polypeptides described herein are useful for preparing pharmaceutical compositions for prevention or treatment of conditions that require immunosuppression, preferably, inflammatory, autoimmune, allergic and infectious diseases and rejection to transplanted organs.

Polynucleotide, polypeptide with immunosuppressive activity, expression cassette, expression vector, host cell, pharmaceutical composition, methods for producing a polypeptide with immunosuppressive activity and for preventing or treating conditions that require immunosuppression, and use of a polypeptide

The present invention relates preferably to the use of 4-bromo-N-[(E)-(2-methyl-1H-indol-3-yl)methyleneamino]benzenesulphonamide and 4-methyl-3-oxo-2-(3-pyridylmethylene) benzo[3,4-b]furan-6-yl-4-chlorobenzenesulphonate (compounds 5 and 6, respectively), which are compounds that can inhibit the toxic activity of sphingomyelinase D fromvenom, controlling the development of cutaneous and systemic loxoscelism; reducing haemolysis; inhibiting the formation of skin lesions; inhibiting skin necrosis; inhibiting intracellular signaling pathways and the production of reactive oxygen species. In addition to the therapeutic potential thereof, said inhibitors can be used to study the activity of sphingomyelinases and phospholipases D. The present invention also relates to a pharmaceutical composition for treating loxoscelism, reducing haemolysis, inhibiting the formation of skin lesions, inhibiting skin necrosis, inhibiting intracellular signaling pathways and the production of reactive oxygen species, comprising said compounds and a pharmaceutically acceptable carrier.

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São Paulo, Brazil

Denise Vilarinho Tambourgi