Resumo
Successful drug development requires a disease target that plays a vital role in the causation and/or progression of the disease phenotype and that can be modulated with a drug molecule. In other words, therapeutically relevant targets are both “disease-modifying” and “druggable”. It has been estimated that around 10% of the entire human genome is involved in disease onset or progression, resulting in approximately 3000 potential targets suitable for therapeutic intervention. Thus, the rapid and reliable identification of the most promising targets for drug discovery efforts would be the major challenge for the pharmaceutical industry. Moreover, the knowledge of the mechanisms that govern the inflammatory process and cell survival, generated by basic research, is essential for the identification and validation of potential and more specific molecular target. Natural products are a rich source of biologically active compounds. Many of today’s medicines are either obtained directly from a natural source or were developed from a lead compound originally obtained from a natural source. Venoms and toxins from animals, plants, snakes, spiders, scorpions, insects, slugs, and microorganisms are extremely potent because the often have very specific interactions with a macromolecular target in the body. As a result, they have proved to be important not only as lead compounds in the development of novel drugs, but also as tools in studying receptors, ion channels, and enzymes. In our research group, interesting bioactive molecules from animal venoms and secretions, such as proteins (wild or recombinant form) and derived-peptides, targeting the homeostatic system and inflammatory events, have been exploited and are in different phases of development. We have been focusing our efforts on understanding their mechanism of action through the exploitation of specific signaling pathways in order to identify and validate novel molecular targets. Among the proteins’ families taken into account are lipocalins, hemolins, serine protease inhibitors, phospholipases and chaperones. In this regard, the main idea is to consider the expertise of the Butantan Institute researchers already have in computer-aided molecular design/bioinformatics/OMICS (transcriptome, proteome) field, molecular and cellular biology and immunology approaches (in vitro assays), and in vivo models and image techniques in order to create a Center of Excellence for Research in Target Discovery. (AU)
Publicações científicas
(19)
(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)
CAMARA, GUILHERME A.;
NISHIYAMA-JR, MILTON Y.;
KITANO, EDUARDO S.;
OLIVEIRA, URSULA C.;
DA SILVA, JR., PEDRO I.;
JUNQUEIRA-DE-AZEVEDO, INACIO L.;
TASHIMA, ALEXANDRE K.
A Multiomics Approach Unravels New Toxins With PossibleIn SilicoAntimicrobial, Antiviral, and Antitumoral Activities in the Venom ofAcanthoscurria rondoniae.
FRONTIERS IN PHARMACOLOGY,
v. 11,
JUL 17 2020.
Citações Web of Science: 0.
MONTONI, FABIO;
ANDREOTTI, DIANA ZUKAS;
DOS SANTOS EICHLER, ROSANGELA APARECIDA;
SANTOS, WELLINGTON DA SILVA;
KISAKI, CAROLINA YUKIKO;
SUEHIRO ARCOS, STEPHANIE SANTOS;
LIMA, ISMAEL FEITOSA;
MALTAURO SOARES, MAGNA APARECIDA;
NISHIYAMA-JR, MILTON YUTAKA;
NAVA-RODRIGUES, DANIEL;
FERRO, EMER SUAVINHO;
CARVALHO, VALDEMIR MELECHCO;
IWAI, LEO KEI.
The impact of rattlesnake venom on mice cerebellum proteomics points to synaptic inhibition and tissue damage.
JOURNAL OF PROTEOMICS,
v. 221,
JUN 15 2020.
Citações Web of Science: 0.
LICHTENSTEIN, FLAVIO;
IQBAL, ASIF;
ALVES DE LIMA WILL, SONIA ELISABETE;
BOSCH, ROSEMARY VIOLA;
DEOCESANO-PEREIRA, CARLOS;
GOLDFEDER, MAURICIO BARBUGIANI;
CHAMMAS, ROGER;
MADUREIRA TRUFEN, CARLOS EDUARDO;
PEREIRA MORAIS, KATIA LUCIANO;
DE SOUZA, JEAN GABRIEL;
MENDONCA NATALINO, RENATO JOSE;
DE AZEVEDO, INACIO JUNQUEIRA;
NISHIYAMA JUNIOR, MILTON YUTAKA;
OLIVEIRA, URSULA;
ARRUDA ALVES, FRANCISCO IVANIO;
ARAUJO, JAQUELINE MAYARA;
MAIA LOBBA, ALINE RAMOS;
CHUDZINSKI-TAVASSI, ANA MARISA.
Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model.
SCIENTIFIC REPORTS,
v. 10,
n. 1
APR 14 2020.
Citações Web of Science: 0.
VIANA, MARIANA N.;
LEIGUEZ, ELBIO;
GUTIERREZ, JOSE M.;
RUCAVADO, ALEXANDRA;
MARKUS, REGINA P.;
MARCOLA, MARINA;
TEIXEIRA, CATARINA;
FERNANDES, CRISTINA M.
A representative metalloprotease induces PGE(2) synthesis in fibroblast-like synoviocytes via the NF-kappa B/COX-2 pathway with amplification by IL-1 beta and the EP4 receptor.
SCIENTIFIC REPORTS,
v. 10,
n. 1
FEB 24 2020.
Citações Web of Science: 0.
SCHMIDT, MARIANA COSTA BRAGA;
MORAIS, KATIA L. P.;
DE ALMEIDA, MAIRA ESTANISLAU SOARES;
IQBAL, ASIF;
GOLDFEDER, MAURICIO BARBUGIANI;
CHUDZINSKI-TAVASSI, ANA MARISA.
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells.
CELL ADHESION & MIGRATION,
v. 14,
n. 1,
p. 129-138,
JAN 1 2020.
Citações Web of Science: 6.
BUFALO, MICHELLE C.;
ALMEIDA, MAIRA E.;
FRANCA, ISABELLA ARAUJO;
ZAMBELLI, VANESSA O.;
SANT'ANNA, MORENA BRAZIL MARTINS;
KIMURA, LOUISE F.;
GIARDINI, ALINE CAROLINA;
CURY, YARA;
SAMPAIO, SANDRA COCCUZZO.
Advanced glycation endproducts produced by in vitro glycation of type I collagen modulate the functional and secretory behavior of dorsal root ganglion cells cultivated in two-dimensional system.
Experimental Cell Research,
v. 382,
n. 2-3
SEP 15 2019.
Citações Web of Science: 0.
ALVAREZ-FLORES, MILYAM P.;
HEBERT, AUDREY;
GOUELLE, CATHY;
GELLER, SARAH;
CHUDZINSKI-TAVASSI, ANA M.;
PELLERIN, LUC.
Neuroprotective effect of rLosac on supplement-deprived mouse cultured cortical neurons involves maintenance of monocarboxylate transporter MCT2 protein levels.
Journal of Neurochemistry,
v. 148,
n. 1,
p. 80-96,
JAN 2019.
Citações Web of Science: 1.
IQBAL, ASIF;
GOLDFEDER, MAURICIO BARBUGIANI;
MARQUES-PORTO, RAFAEL;
ASIF, HUMA;
DE SOUZA, JEAN GABRIEL;
FARIA, FERNANDA;
CHUDZINSKI-TAVASSI, ANA MARISA.
Revisiting antithrombotic therapeutics; sculptin, a novel specific, competitive, reversible, scissile and tight binding inhibitor of thrombin.
SCIENTIFIC REPORTS,
v. 7,
MAY 3 2017.
Citações Web of Science: 3.
BRANCO, VANIA G.;
IQBAL, ASIF;
ALVAREZ-FLORES, MIRYAM P.;
SCIANI, JULIANA M.;
DE ANDRADE, SONIA A.;
IWAI, LEO K.;
SERRANO, SOLANGE M. T.;
CHUDZINSKI-TAVASSI, ANA M.
Amblyomin-X having a Kunitz-type homologous domain, is a noncompetitive inhibitor of FXa and induces anticoagulation in vitro and in vivo.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,
v. 1864,
n. 10,
p. 1428-1435,
OCT 2016.
Citações Web of Science: 6.
DE SOUZA, JEAN GABRIEL;
MORAIS, KATIA L. P.;
ANGLES-CANO, EDUARDO;
BOUFLEUR, PAMELA;
DE MELLO, EVANDRO SOBROZA;
MARIA, DURVANEI AUGUSTO;
TAEMI ORIGASSA, CLARICE SILVIA;
ZAMPOLLI, HAMILTON DE CAMPOS;
SARAIVA CAMARA, NIELS OLSEN;
BERRA, CAROLINA MARIA;
BOSCH, ROSEMARY VIOLA;
CHUDZINSKI-TAVASSI, ANA MARISA.
Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model.
ONCOTARGET,
v. 7,
n. 38,
p. 62255-62266,
SEP 20 2016.
Citações Web of Science: 6.