Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly

So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regul...

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Autores principales:	Pravin Kumar Ankush Jagtap, Tomáš Kubelka, Komal Soni, Cindy L. Will, Divita Garg, Claudia Sippel, Tobias G. Kapp, Harish Kumar Potukuchi, Kenji Schorpp, Kamyar Hadian, Horst Kessler, Reinhard Lührmann, Felix Hausch, Thorsten Bach, Michael Sattler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/816cddccf4d4425e993bdca998fb63bd
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spelling	oai:doaj.org-article:816cddccf4d4425e993bdca998fb63bd2021-12-02T17:31:41ZIdentification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly10.1038/s41467-020-19514-12041-1723https://doaj.org/article/816cddccf4d4425e993bdca998fb63bd2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41467-020-19514-1https://doaj.org/toc/2041-1723So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.Pravin Kumar Ankush JagtapTomáš KubelkaKomal SoniCindy L. WillDivita GargClaudia SippelTobias G. KappHarish Kumar PotukuchiKenji SchorppKamyar HadianHorst KesslerReinhard LührmannFelix HauschThorsten BachMichael SattlerNature PortfolioarticleScienceQENNature Communications, Vol 11, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Pravin Kumar Ankush Jagtap Tomáš Kubelka Komal Soni Cindy L. Will Divita Garg Claudia Sippel Tobias G. Kapp Harish Kumar Potukuchi Kenji Schorpp Kamyar Hadian Horst Kessler Reinhard Lührmann Felix Hausch Thorsten Bach Michael Sattler Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
description	So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.
format	article
author	Pravin Kumar Ankush Jagtap Tomáš Kubelka Komal Soni Cindy L. Will Divita Garg Claudia Sippel Tobias G. Kapp Harish Kumar Potukuchi Kenji Schorpp Kamyar Hadian Horst Kessler Reinhard Lührmann Felix Hausch Thorsten Bach Michael Sattler
author_facet	Pravin Kumar Ankush Jagtap Tomáš Kubelka Komal Soni Cindy L. Will Divita Garg Claudia Sippel Tobias G. Kapp Harish Kumar Potukuchi Kenji Schorpp Kamyar Hadian Horst Kessler Reinhard Lührmann Felix Hausch Thorsten Bach Michael Sattler
author_sort	Pravin Kumar Ankush Jagtap
title	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
title_short	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
title_full	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
title_fullStr	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
title_full_unstemmed	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
title_sort	identification of phenothiazine derivatives as uhm-binding inhibitors of early spliceosome assembly
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/816cddccf4d4425e993bdca998fb63bd
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Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly

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