Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition

Daniele Fancelli; Daniela Berta; Simona Bindi; Alexander Cameron; Paolo Cappella; Patrizia Carpinelli; Cornel Catana; Barbara Forte; Patrizia Giordano; Maria Laura Giorgini; Sergio Mantegani; Aurelio Marsiglio; Maurizio Meroni; Juergen Moll; Valeria Pittalà; Fulvia Roletto; Dino Severino; Chiara Soncini; Paola Storici; Roberto Tonani; Mario Varasi; Anna Vulpetti; Paola Vianello

doi:10.1021/jm049076m

Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition

Daniele Fancelli (Lead / Corresponding author), Daniela Berta, Simona Bindi, Alexander Cameron, Paolo Cappella, Patrizia Carpinelli, Cornel Catana, Barbara Forte, Patrizia Giordano, Maria Laura Giorgini, Sergio Mantegani, Aurelio Marsiglio, Maurizio Meroni, Juergen Moll, Valeria Pittalà, Fulvia Roletto, Dino Severino, Chiara Soncini, Paola Storici, Roberto TonaniMario Varasi, Anna Vulpetti, Paola Vianello

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

148 Citations (Scopus)

Abstract

Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC ₅₀ of 0.027 μM in the enzymatic assay for Aur-A inhibition and IC₅₀s between 0.05 μM and 0.5 μM for the inhibition of proliferation of different tumor cell lines.

Original language	English
Pages (from-to)	3080-3084
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	8
Early online date	10 Mar 2005
DOIs	https://doi.org/10.1021/jm049076m
Publication status	Published - 21 Apr 2005

Keywords

Cells
Inhibition
Kinase inhibitors
Peptides and proteins
Scaffolds

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm049076m

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Fancelli, D., Berta, D., Bindi, S., Cameron, A., Cappella, P., Carpinelli, P., Catana, C., Forte, B., Giordano, P., Giorgini, M. L., Mantegani, S., Marsiglio, A., Meroni, M., Moll, J., Pittalà, V., Roletto, F., Severino, D., Soncini, C., Storici, P., ... Vianello, P. (2005). Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. Journal of Medicinal Chemistry, 48(8), 3080-3084. https://doi.org/10.1021/jm049076m

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title = "Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition",

abstract = "Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC 50 of 0.027 μM in the enzymatic assay for Aur-A inhibition and IC50s between 0.05 μM and 0.5 μM for the inhibition of proliferation of different tumor cell lines.",

keywords = "Cells, Inhibition, Kinase inhibitors, Peptides and proteins, Scaffolds",

author = "Daniele Fancelli and Daniela Berta and Simona Bindi and Alexander Cameron and Paolo Cappella and Patrizia Carpinelli and Cornel Catana and Barbara Forte and Patrizia Giordano and Giorgini, {Maria Laura} and Sergio Mantegani and Aurelio Marsiglio and Maurizio Meroni and Juergen Moll and Valeria Pittal{\`a} and Fulvia Roletto and Dino Severino and Chiara Soncini and Paola Storici and Roberto Tonani and Mario Varasi and Anna Vulpetti and Paola Vianello",

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doi = "10.1021/jm049076m",

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Fancelli, D, Berta, D, Bindi, S, Cameron, A, Cappella, P, Carpinelli, P, Catana, C, Forte, B, Giordano, P, Giorgini, ML, Mantegani, S, Marsiglio, A, Meroni, M, Moll, J, Pittalà, V, Roletto, F, Severino, D, Soncini, C, Storici, P, Tonani, R, Varasi, M, Vulpetti, A & Vianello, P 2005, 'Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition', Journal of Medicinal Chemistry, vol. 48, no. 8, pp. 3080-3084. https://doi.org/10.1021/jm049076m

TY - JOUR

T1 - Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition

AU - Fancelli, Daniele

AU - Berta, Daniela

AU - Bindi, Simona

AU - Cameron, Alexander

AU - Cappella, Paolo

AU - Carpinelli, Patrizia

AU - Catana, Cornel

AU - Forte, Barbara

AU - Giordano, Patrizia

AU - Giorgini, Maria Laura

AU - Mantegani, Sergio

AU - Marsiglio, Aurelio

AU - Meroni, Maurizio

AU - Moll, Juergen

AU - Pittalà, Valeria

AU - Roletto, Fulvia

AU - Severino, Dino

AU - Soncini, Chiara

AU - Storici, Paola

AU - Tonani, Roberto

AU - Varasi, Mario

AU - Vulpetti, Anna

AU - Vianello, Paola

PY - 2005/4/21

Y1 - 2005/4/21

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AB - Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC 50 of 0.027 μM in the enzymatic assay for Aur-A inhibition and IC50s between 0.05 μM and 0.5 μM for the inhibition of proliferation of different tumor cell lines.

KW - Cells

KW - Inhibition

KW - Kinase inhibitors

KW - Peptides and proteins

KW - Scaffolds

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SN - 0022-2623

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EP - 3084

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 8

ER -

Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition

Abstract

Keywords

ASJC Scopus subject areas

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