T
Tod Smeal
Researcher at Pfizer
Publications - 43
Citations - 3680
Tod Smeal is an academic researcher from Pfizer. The author has contributed to research in topics: Crizotinib & Anaplastic lymphoma kinase. The author has an hindex of 24, co-authored 43 publications receiving 3207 citations. Previous affiliations of Tod Smeal include Eli Lilly and Company.
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Journal ArticleDOI
Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F.
Alice T. Shaw,Luc Friboulet,Ignaty Leshchiner,Justin F. Gainor,Bergqvist S,Alexei Brooun,Benjamin J. Burke,Ya-Li Deng,W. Liu,Leila Dardaei,Rosa L. Frias,Katherine Schultz,Jennifer A. Logan,Leonard P. James,Tod Smeal,Sergei Timofeevski,Ryohei Katayama,Anthony J. Iafrate,Long P. Le,Michele McTigue,Gad Getz,Ted William Johnson,J. A. Engelman +22 more
TL;DR: In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain, and sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation.
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Discovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations
Ted William Johnson,Paul F. Richardson,Simon Bailey,Alexei Brooun,Benjamin J. Burke,Michael R. Collins,J. Jean Cui,Deal Judith G,Ya-Li Deng,Dac M. Dinh,Lars D. Engstrom,Mingying He,Jacqui Elizabeth Hoffman,Robert Louis Hoffman,Qinhua Huang,Robert Steven Kania,John Charles Kath,Hieu Lam,Justine L. Lam,Phuong Le,Laura Lingardo,Wei Liu,Michele McTigue,Cynthia Louise Palmer,Neal W. Sach,Tod Smeal,Graham L. Smith,A.E. Stewart,Sergei Timofeevski,Huichun Zhu,Jinjiang Zhu,Helen Y. Zou,Martin Paul Edwards +32 more
TL;DR: This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity, which was found to be potent against wild-type ALK and clinically reported ALK kinase domain mutations.
Journal ArticleDOI
PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models.
Helen Y. Zou,Luc Friboulet,David P. Kodack,Lars D. Engstrom,Qiuhua Li,Melissa West,Ruth W. Tang,Hui Wang,Konstantinos Tsaparikos,Jinwei Wang,Sergei Timofeevski,Ryohei Katayama,Dac M. Dinh,Hieu Lam,Justine L. Lam,Shinji Yamazaki,Wenyue Hu,Bhushankumar Patel,Divya Bezwada,Rosa L. Frias,Eugene Lifshits,Sidra Mahmood,Justin F. Gainor,Timothy Affolter,Patrick B. Lappin,Hovhannes J. Gukasyan,Nathan V. Lee,Shibing Deng,Rakesh K. Jain,Ted William Johnson,Alice T. Shaw,Valeria Fantin,Tod Smeal +32 more
TL;DR: The results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases.
Journal ArticleDOI
Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth
Brion W. Murray,Chuangxing Guo,Joseph Piraino,John Westwick,Cathy Zhang,Jane Lamerdin,Eleanor Dagostino,Daniel R. Knighton,Cho-Ming Loi,Michael Zager,Eugenia Kraynov,Ian Popoff,James G. Christensen,Ricardo Martinez,Kephart Susan Elizabeth,Marakovits Joseph T,Karlicek Shannon Marie,Simon Bergqvist,Tod Smeal +18 more
TL;DR: PAK4-related pathways are defined, additional support for PAK4 as a therapeutic target with a unique combination of functions (apoptotic, cytoskeletal, cell-cycle), and a potent, orally available small-molecule PAK inhibitor with significant promise for the treatment of human cancers is identified.
Journal ArticleDOI
Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines.
Marinella G. Callow,Felix Clairvoyant,Shirley Zhu,Brian Schryver,David Whyte,James R. Bischoff,Bahija Jallal,Tod Smeal +7 more
TL;DR: It is demonstrated that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins and identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK 4 in vivo, and suggested thatPAK4 activity is required for Ras-driven, anchorage-independent growth.