Dr. Pellecchia is developing compounds that defeat Bc1-2 family proteins and could improve the effectiveness of many cancer treatments.
Dr. Pellecchia received his Ph.D. in pharmaceutical sciences at the University of Naples, Italy.
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A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy.
Placzek WJ, Wei J, Kitada S, Zhai D, Reed JC, Pellecchia M
Cell Death Dis. 2010;1:e40
A novel pharmacophore model for the design of anthrax lethal factor inhibitors.
Yuan H, Johnson SL, Chen LH, Wei J, Pellecchia M
Chem Biol Drug Des. 2010 Sep 1;76(3):263-8
NMR-based design and evaluation of novel bidentate inhibitors of the protein tyrosine phosphatase YopH.
Leone M, Barile E, Vazquez J, Mei A, Guiney D, Dahl R, Pellecchia M
Chem Biol Drug Des. 2010 Jul;76(1):10-6
BI-97C1, an optically pure Apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins.
Wei J, Stebbins JL, Kitada S, Dash R, Placzek W, Rega MF, Wu B, Cellitti J, Zhai D, Yang L, Dahl R, Fisher PB, Reed JC, Pellecchia M
J Med Chem. 2010 May 27;53(10):4166-76
Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors.
De SK, Chen V, Stebbins JL, Chen LH, Cellitti JF, Machleidt T, Barile E, Riel-Mehan M, Dahl R, Yang L, Emdadi A, Murphy R, Pellecchia M
Bioorg Med Chem. 2010 Jan 15;18(2):590-6
Identification of lead compounds as antagonists of protein Bcl-xL with a diversity-oriented multidisciplinary approach.
Di Micco S, Vitale R, Pellecchia M, Rega MF, Riva R, Basso A, Bifulco G
J Med Chem. 2009 Dec 10;52(23):7856-67
The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam.
Leone M, Cellitti J, Pellecchia M
BMC Struct Biol. 2009;9:59
Small molecule DnaK modulators targeting the beta-domain.
Cellitti J, Zhang Z, Wang S, Wu B, Yuan H, Hasegawa P, Guiney DG, Pellecchia M
Chem Biol Drug Des. 2009 Oct;74(4):349-57
Apogossypol derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins.
Wei J, Kitada S, Rega MF, Stebbins JL, Zhai D, Cellitti J, Yuan H, Emdadi A, Dahl R, Zhang Z, Yang L, Reed JC, Pellecchia M
J Med Chem. 2009 Jul 23;52(14):4511-23
Maurizio Pellecchia's Research Focus
Cancer, Infectious Diseases
Dr. Pellecchia’s research focuses on the characterization of intermolecular interactions, on the determination of protein structures and on the development of small molecule inhibitors of protein targets involved in cell-signaling, virulence factors and host-pathogens interactions. The resulting compounds are then used as molecular probes to provide further understanding on the mechanism of action of their respective targets. The overall goal of the laboratory is to successfully bring together basic sciences involving modern nuclear magnetic resonance spectroscopy (NMR) techniques, computer modeling and traditional medicinal chemistry to elucidate the molecular basis of disease and to develop novel therapeutic compounds. Amongst the several projects that Dr. Pellecchia’s laboratory have initiated in the past years, noteworthy are the discovery, characterization and further development of potential therapeutic compounds targeting proteins of the Bcl-2 family, such as Bcl-xL and Bcl-2 (cancer targets) as well as Bid (involved in neurodegenerative diseases) and protein kinases such as p38 and Jnk (inflammation and diabetes). In addition, other very active areas of research involve the development of antitoxin compounds targeting the Anthrax metalloproteinase LF and protein components of the type-III secretion system, common to many pathogens, including Yersinia pestis and Salmonella. Finally, an area in which Dr. Pellecchia remains particularly interested is the development of novel NMR-based techniques to aid the characterization of protein structure, protein-protein and protein-ligand interactions using NMR spectroscopy. The design and synthesis of several high affinity ligands, for example, was made possible by the SAR by ILOEs approach, a NMR-based method developed in Dr. Pellecchia’s laboratory that enables the identification of high affinity ligands for a given protein target.
About Maurizio Pellecchia
Dr. Pellecchia is a medicinal chemist with a strong background in biophysics and NMR-based drug design. He trained at the University of Naples (Italy) where he obtained his Ph.D. in Pharmaceutical Sciences, at the ETH-Zurich (working with 2002 Nobel Laureate Prof. Dr. Kurt Wüthrich) and the University of Michigan. Prior to his recruitment at Sanford-Burnham Medical Research Institute as Associate Professor, Dr. Pellecchia spent a few years in the pharmaceutical industry. Dr. Pellecchia was promoted to full Professor in June 2007. Dr. Pellecchia's laboratory is centered on the characterization of intermolecular interactions, protein structure and on the development of small molecule inhibitors in systems involved in cell-signaling and apoptosis for the treatment of several human diseases including cancer, neurodegeneration and infectious diseases.