Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer

Autor: Kelly Slocum, Jianmei Fan, Michael Dore, Palermo Mark G, Zhan Deng, Bakary-Barry Toure, Jorge Garcia-Fortanet, Dyuti Majumdar, Martin F. Hentemann, Nick Keen, Suzanne Zhu, Christopher Towler, Michael Shultz, William R. Sellers, Simon Mathieu, Denise Grunenfelder, Robert Koenig, Douglas C. Bauer, Shumei Liu, Jay Larrow, Victoriano Tamez, David Dunstan, Andreea Argintaru, Timothy Michael Ramsey, Zhouliang Chen, Gang Liu, Ying-Nan Chen, Rukundo Ntaganda, Bing Yu, Joanna Slisz, Hongyun Wang, Pascal D. Fortin, Christopher Sean Straub, Ji-Hu Zhang, Ping Wang, Laura R. LaBonte, Mitsunori Kato, Matthew J. Meyer, Fan Yang, Patrick James Sarver, Samuel B. Ho, Brant Firestone, Rajesh Karki, John F. Reilly, Troy Smith, Ho Man Chan, Cary Fridrich, John William Giraldes, Julie Boisclair, Chen Christine Hiu-Tung, Meir Glick, Zhao B. Kang, Morvarid Mohseni, Lawrence Blas Perez, Michael G. Acker, Sarah Williams, Matthew J. LaMarche, Martin Sendzik, Michelle Fodor, Huia-Xiang Hao, Peter Fekkes, Minying Pu, Travis Stams, Stanley Spence, Andriana Jouk

Publikováno v: Journal of medicinal chemistry. 63(22)

SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::345804676325a445ebbb9ef600ced79a
https://pubmed.ncbi.nlm.nih.gov/32910655

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

Autor: Palermo Mark G, Timothy Michael Ramsey, Ping Zhu, Shumei Liu, Jay Larrow, Laura R. La Bonte, Rajesh Karki, Chen Christine Hiu-Tung, Kavitha Venkatesan, Jaison Jacob, Pascal D. Fortin, Francois Lenoir, Hui Gao, Guizhi Yang, Matthew J. Meyer, Ji-Hu Zhang, William R. Sellers, Michael Shultz, Denise Grunenfelder, Edmund Price, Jorge Garcia-Fortanet, Feng Fei, Zhouliang Chen, Gang Liu, Vesselina G. Cooke, Jing Yuan, Michelle Fodor, Ping Wang, Minying Pu, Nicholas Keen, Samuel B. Ho, Kathy Hsiao, Markus Warmuth, Travis Stams, Christopher Quinn, Mitsunori Kato, Subarna Shakya, Sarah Williams, Dyuti Majumdar, Peter Fekkes, Michael G. Acker, Cary Fridrich, Joanna Slisz, Huaixiang Hao, Matthew J. LaMarche, Ying-Nan P. Chen, Brandon Antonakos, Jason R. Dobson, Brant Firestone, Lawrence Blas Perez, Zhao B. Kang, Ho Man Chan, Zhan Deng

Publikováno v: Nature. 535:148-152

SHP099, a selective inhibitor of signalling meditator SHP2 with drug-like properties, has an allosteric mechanism of action whereby it stabilizes SHP2 in an auto-inhibited conformation, and suppresses RAS–ERK signalling and proliferation in recepto

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::f58ee0fa5f3f5109027ba2125d369122
https://doi.org/10.1038/nature18621