PF-06459988 / Pfizer - LARVOL DELTA

Engineering electrophile-sensitive kinase mutants to accelerate oncology target validation (ACS-Fall 2022) - "Pancreatic cancer cells homozygous for MASTL Asp117Cys showed clear dose-dependent growth inhibition when treated with a T790M mutant-specific EGFR covalent inhibitor (PF-06459988)...Herein our application of an electrophile-sensitive mutant demonstrates how existing, optimized covalent small molecule inhibitors can be repurposed as chemical probes against engineered kinase domains. This engineered system provides a valuable orthogonal benchmark in advance of a drug discovery campaign, reveals target-dependent biology, and is likely to translate to additional kinase targets due to structural conservation within this enzymatic domain."

Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • JAK3

[VIRTUAL] Engineering electrophile-sensitive kinase mutants to accelerate oncology target validation (AACR 2021) - "Pancreatic cancer cells homozygous for MASTL Asp117Cys showed clear dose-dependent growth inhibition when treated with a T790M mutant-specific EGFR covalent inhibitor (PF-06459988)...Herein our application of an electrophile-sensitive mutant demonstrates how existing, optimized covalent small molecule inhibitors can be repurposed as chemical probes against engineered kinase domains. This engineered system provides a valuable orthogonal benchmark in advance of a drug discovery campaign, reveals target-dependent biology, and is likely to translate to additional kinase targets due to structural conservation within this enzymatic domain."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • JAK3