Targeting GLI proteins in human cancer by small molecules (WO2014116651 A1): a patent evaluation

Expert Opinion on Therapeutic Patents
M Kyle Hadden

Abstract

The invention reviewed in this patent evaluation is the synthesis and application of small molecule inhibitors of Gli transcriptional activity as potential anticancer agents. The oncogenic nature of Gli proteins has been traditionally associated with the hedgehog (Hh) signaling pathway; however, the recent identification of aberrant Gli activation unrelated to Hh signaling has prompted drug discovery efforts directly targeting Gli proteins. The central core of the compounds described in this patent (WO2014116651 A1) is structurally analogous to the pyrazoline scaffold previously disclosed by these inventors. Data describing the inhibitory activity of these compounds against the Hh pathway in vitro and in Hh-dependent in vivo models of human cancer are not provided. For this patent disclosure, the inventors primarily focus on the anticancer properties of their compounds in lung and lung-related malignancies. The compounds are moderately active in these models, but they do not exhibit the overall preclinical profile generally required for advancement into clinical trials.

References

Mar 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Barbara SteccaAriel Ruiz I Altaba
Mar 22, 2008·Chembiochem : a European Journal of Chemical Biology·Takahiro HosoyaMasami Ishibashi
Dec 17, 2008·Developmental Cell·Jin Jiang, Chi-Chung Hui
Oct 1, 2010·Science Translational Medicine·Silvia BuonamiciMarion Dorsch
Dec 21, 2010·Organic & Biomolecular Chemistry·Midori A AraiMasami Ishibashi
Apr 18, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Laurence BrugièresJacques Grill
Apr 18, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tenley C ArcherScott L Pomeroy
May 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Michelle J LeeJames M Olson
Aug 23, 2012·Archives of Dermatology·Anne Lynn S Chang, Anthony E Oro
Nov 10, 2013·Nature Medicine·Dereck AmakyeMarion Dorsch
Jan 24, 2014·Beilstein Journal of Organic Chemistry·Midori A AraiMasami Ishibashi
Apr 25, 2014·Journal of Experimental & Clinical Cancer Research : CR·Dongsheng YueBiao He
May 23, 2014·Expert Opinion on Drug Discovery·Upasana Banerjee, Matthew Kyle Hadden
Dec 6, 2014·The EMBO Journal·Paola InfanteLucia Di Marcotullio

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Citations

Dec 17, 2015·Expert Opinion on Therapeutic Patents·Fabrizio Manetti, Elena Petricci

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