H
Hieu Lam
Researcher at Pfizer
Publications - 12
Citations - 1422
Hieu Lam is an academic researcher from Pfizer. The author has contributed to research in topics: Anaplastic lymphoma kinase & Crizotinib. The author has an hindex of 8, co-authored 12 publications receiving 1165 citations.
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Journal ArticleDOI
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
Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance
Ping Chen,Nathan V. Lee,Wenyue Hu,Meirong Xu,Rose Ann Ferre,Hieu Lam,Simon Bergqvist,James Solowiej,Wade Diehl,You-Ai He,Xiu Yu,Asako Nagata,Todd VanArsdale,Brion W. Murray +13 more
TL;DR: Therapeutically targeting aberrant intracellular kinase signaling is attractive from a biological perspective but drug development is often hindered by toxicities and inadequate efficacy, so understanding the molecular components of potency and selectivity facilitates rational design of future generations of kinase-directed drugs.
ComponentDOI
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 Alk/Ros1 with Pre-Clinical 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,Jean Cui,Deal Judith G,Ya-Li Deng,Dac M. Dinh,Lars D. Engstrom,Mingying He,Jacqui Elizabeth Hoffman,Robert Louis Hoffman,Qinhua Huang,John Charles Kath,Robert Steven Kania,Hieu Lam,Justine L. Lam,P.T. Le,Laura Lingardo,Wei Liu,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
Journal ArticleDOI
Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib
Qinhua Huang,Ted William Johnson,Simon Bailey,Alexei Brooun,Kevin D. Bunker,Benjamin J. Burke,Michael R. Collins,Andrew Simon Cook,J. Jean Cui,Dack Kevin Neil,Deal Judith G,Ya-Li Deng,Dac M. Dinh,Lars D. Engstrom,Mingying He,Jacqui Elizabeth Hoffman,Robert Louis Hoffman,Patrick S. Johnson,Robert Steven Kania,Hieu Lam,Justine L. Lam,Phuong Le,Qiuhua Li,Laura Lingardo,Wei Liu,Melissa West Lu,Michele McTigue,Cynthia Louise Palmer,Paul F. Richardson,Neal W. Sach,Hong Shen,Tod Smeal,Graham L. Smith,A.E. Stewart,Sergei Timofeevski,Konstantinos Tsaparikos,Hui Wang,Huichun Zhu,Jinjiang Zhu,Helen Y. Zou,Martin Paul Edwards +40 more
TL;DR: The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e, which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclinical pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).