Biological characterization of 8-cyclopropyl-2-(Pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8h)-one, a promising inhibitor of DYRK1A

Corinne Fruit; Florence Couly; Rahul Bhansali; Malini Rammohan; Mattias F. Lindberg; John D. Crispino; Laurent Meijer; Thierry Besson

doi:10.3390/ph12040185

Biological characterization of 8-cyclopropyl-2-(Pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8h)-one, a promising inhibitor of DYRK1A

Corinne Fruit, Florence Couly, Rahul Bhansali, Malini Rammohan, Mattias F. Lindberg, John D. Crispino, Laurent Meijer, Thierry Besson^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

9 Scopus citations

Abstract

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f ]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610).

Original language	English (US)
Article number	185
Journal	Pharmaceuticals
Volume	12
Issue number	4
DOIs	https://doi.org/10.3390/ph12040185
State	Published - Dec 2019

Funding

Financial support from the MESR (French Minist?re de l?Enseignement Sup?rieur & de la Recherche) is gratefully acknowledged for the doctoral fellowships to F.C. C.F., F.C., and T.B. thank the LABEX SynOrg (ANR-11-LABX-0029) for financial support. This research was supported by grants from the ?Fonds Unique Interminist?riel? (FUI) TRIAD project and Conseil R?gional de Bretagne (L.M.) and the ?Fondation J?r?me Lejeune? (L.M.). Acknowledgments: SH-SY5Y-Tau4R cells were gifts from Fred Van Leuven (Leuven, Belgium). T.B. thank P. Bonnet and J. Diharce for providing the figure of the graphical abstract. Funding: Financial support from the MESR (French Ministère de l’Enseignement Supérieur & de la Recherche) is gratefully acknowledged for the doctoral fellowships to F.C. C.F., F.C., and T.B. thank the LABEX SynOrg (ANR-11-LABX-0029) for financial support. This research was supported by grants from the “Fonds Unique Interministériel” (FUI) TRIAD project and Conseil Régional de Bretagne (L.M.) and the “Fondation Jérôme Lejeune” (L.M.).

Keywords

CMGC kinases
DYRK family kinases
Pre-B cells
Quiescence
SH-SY5Y-Tau-4R cells
Thiazolo[5,4-f]quinazolin-9(8H)-one

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Pharmaceutical Science

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10.3390/ph12040185

Cite this

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title = "Biological characterization of 8-cyclopropyl-2-(Pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8h)-one, a promising inhibitor of DYRK1A",

abstract = "Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f ]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610).",

keywords = "CMGC kinases, DYRK family kinases, Pre-B cells, Quiescence, SH-SY5Y-Tau-4R cells, Thiazolo[5,4-f]quinazolin-9(8H)-one",

author = "Corinne Fruit and Florence Couly and Rahul Bhansali and Malini Rammohan and Lindberg, {Mattias F.} and Crispino, {John D.} and Laurent Meijer and Thierry Besson",

note = "Funding Information: Funding: Financial support from the MESR (French Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur & de la Recherche) is gratefully acknowledged for the doctoral fellowships to F.C. C.F., F.C., and T.B. thank the LABEX SynOrg (ANR-11-LABX-0029) for financial support. This research was supported by grants from the “Fonds Unique Interminist{\'e}riel” (FUI) TRIAD project and Conseil R{\'e}gional de Bretagne (L.M.) and the “Fondation J{\'e}r{\^o}me Lejeune” (L.M.). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

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doi = "10.3390/ph12040185",

language = "English (US)",

volume = "12",

journal = "Pharmaceuticals",

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AU - Fruit, Corinne

AU - Couly, Florence

AU - Bhansali, Rahul

AU - Rammohan, Malini

AU - Lindberg, Mattias F.

AU - Crispino, John D.

AU - Meijer, Laurent

AU - Besson, Thierry

N1 - Funding Information: Funding: Financial support from the MESR (French Ministère de l’Enseignement Supérieur & de la Recherche) is gratefully acknowledged for the doctoral fellowships to F.C. C.F., F.C., and T.B. thank the LABEX SynOrg (ANR-11-LABX-0029) for financial support. This research was supported by grants from the “Fonds Unique Interministériel” (FUI) TRIAD project and Conseil Régional de Bretagne (L.M.) and the “Fondation Jérôme Lejeune” (L.M.). Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/12

Y1 - 2019/12

N2 - Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f ]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610).

AB - Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f ]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610).

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KW - Quiescence

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Biological characterization of 8-cyclopropyl-2-(Pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8h)-one, a promising inhibitor of DYRK1A

Abstract

Funding

Keywords

ASJC Scopus subject areas

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