Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo
The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2019-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-019-12996-8 |
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doaj-a5398760f41b41118e32f8afccdebe492021-05-11T12:24:48ZengNature Publishing GroupNature Communications2041-17232019-11-0110111510.1038/s41467-019-12996-8Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivoTamer S. Kaoud0William H. Johnson1Nancy D. Ebelt2Andrea Piserchio3Diana Zamora-Olivares4Sabrina X. Van Ravenstein5Jacey R. Pridgen6Ramakrishna Edupuganti7Rachel Sammons8Micael Cano9Mangalika Warthaka10Matthew Harger11Clint D. J. Tavares12Jihyun Park13Mohamed F. Radwan14Pengyu Ren15Eric V. Anslyn16Kenneth Y. Tsai17Ranajeet Ghose18Kevin N. Dalby19Division of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDepartment of Chemistry and Biochemistry, The City College of New YorkDepartment of Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinBiomedical Engineering Department, The University of Texas at AustinDepartment of Cancer Biology, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical SchoolThe University of Texas MD Anderson Cancer CenterDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz UniversityBiomedical Engineering Department, The University of Texas at AustinDepartment of Chemistry, The University of Texas at AustinMoffitt Cancer CenterDepartment of Chemistry and Biochemistry, The City College of New YorkDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at AustinThe ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.https://doi.org/10.1038/s41467-019-12996-8 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Tamer S. Kaoud William H. Johnson Nancy D. Ebelt Andrea Piserchio Diana Zamora-Olivares Sabrina X. Van Ravenstein Jacey R. Pridgen Ramakrishna Edupuganti Rachel Sammons Micael Cano Mangalika Warthaka Matthew Harger Clint D. J. Tavares Jihyun Park Mohamed F. Radwan Pengyu Ren Eric V. Anslyn Kenneth Y. Tsai Ranajeet Ghose Kevin N. Dalby |
| spellingShingle |
Tamer S. Kaoud William H. Johnson Nancy D. Ebelt Andrea Piserchio Diana Zamora-Olivares Sabrina X. Van Ravenstein Jacey R. Pridgen Ramakrishna Edupuganti Rachel Sammons Micael Cano Mangalika Warthaka Matthew Harger Clint D. J. Tavares Jihyun Park Mohamed F. Radwan Pengyu Ren Eric V. Anslyn Kenneth Y. Tsai Ranajeet Ghose Kevin N. Dalby Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo Nature Communications |
| author_facet |
Tamer S. Kaoud William H. Johnson Nancy D. Ebelt Andrea Piserchio Diana Zamora-Olivares Sabrina X. Van Ravenstein Jacey R. Pridgen Ramakrishna Edupuganti Rachel Sammons Micael Cano Mangalika Warthaka Matthew Harger Clint D. J. Tavares Jihyun Park Mohamed F. Radwan Pengyu Ren Eric V. Anslyn Kenneth Y. Tsai Ranajeet Ghose Kevin N. Dalby |
| author_sort |
Tamer S. Kaoud |
| title |
Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo |
| title_short |
Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo |
| title_full |
Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo |
| title_fullStr |
Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo |
| title_full_unstemmed |
Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo |
| title_sort |
modulating multi-functional erk complexes by covalent targeting of a recruitment site in vivo |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2019-11-01 |
| description |
The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice. |
| url |
https://doi.org/10.1038/s41467-019-12996-8 |
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