• Publications
  • Influence
Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.
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. This mutation is predictedExpand
  • 294
  • 14
  • PDF
PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models.
We report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potencyExpand
  • 252
  • 11
  • PDF
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
Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops. ResistantExpand
  • 215
  • 8
Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. pcc 6803.
Genes encoding enzymes of the biosynthetic pathway leading to phylloquinone, the secondary electron acceptor of photosystem (PS) I, were identified in Synechocystis sp. PCC 6803 by comparison withExpand
  • 128
  • 6
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations
  • H. Zou, Q. Li, +20 authors V. Fantin
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
  • 2 March 2015
Significance Overcoming resistance to targeted kinase inhibitors is a major clinical challenge in oncology. Development of crizotinib resistance through the emergence of a secondary ROS1 mutation,Expand
  • 151
  • 5
  • PDF
Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK Mutations in ALK-Positive Lung Cancer.
The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor lorlatinib hasExpand
  • 79
  • 5
Using the Golden Triangle to optimize clearance and oral absorption.
The Golden Triangle is a visualization tool developed from in vitro permeability, in vitro clearance and computational data designed to aid medicinal chemists in achieving metabolically stable,Expand
  • 156
  • 4
  • PDF
Recruitment of a Foreign Quinone into the A1 Site of Photosystem I
Interruption of the phylloquinone (PhQ) biosynthetic pathway by interposon mutagenesis of themenA and menB genes inSynechocystis sp. PCC 6803 results in plastoquinone-9 (PQ-9) occupying the A1 siteExpand
  • 63
  • 2
Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib.
Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients.Expand
  • 62
  • 2
Effects of Renal Function on Crizotinib Pharmacokinetics: Dose Recommendations for Patients with ALK-Positive Non-Small Cell Lung Cancer
Background and ObjectivesCrizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC). TheExpand
  • 9
  • 2
  • PDF