Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: 2 H -pyrazolo[3,4- d ]pyrimidin-4-amine derivatives as novel selective fibroblast growth factor receptor 2 (FGFR2) inhibitors

doi: 10.1080/14756366.2026.2647526

Figure Lengend Snippet: PLW559 covalently binds to FGFR2 kinase. (A) Antiproliferative effects of PLW559 and PLW14N against BaF3-FGFR1, BaF3-FGFR2 and parental BaF3 cell lines; (B) Docking results of PLW559 with FGFR2; (C) Deconvoluted intact mass spectra of unmodified FGFR2 (top) and PLW559 -labeled FGFR2 (bottom), acquired with 1 μg of protein; (D) Higher energy collision-induced dissociation (HCD) MS/MS spectrum of the [M + 2H] 2+ ion at m/z 1251.581, derived from the human FGFR2 peptide PLGEGCFGQVVMAEAVGIDK containing one modified site. Predicted b- and y-type ions (partial list) are indicated above and below the peptide sequence, respectively.

Article Snippet: PLW559 was preincubated with FGFR1, FGFR2, FGFR3 or FGFR4 kinase (Carna Biosciences) and substrate peptide (Peptide30, GL) in 50 mmol/L HEPES, pH 7.5, 10 mmol/L MgCl 2 , 1 mmol/L EGTA, 0.01% Brij-35, 2 mmol/L DTT, and 0.05% BSA for 30 min at room temperature.

Techniques: Labeling, Tandem Mass Spectroscopy, Derivative Assay, Modification, Sequencing

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: 2 H -pyrazolo[3,4- d ]pyrimidin-4-amine derivatives as novel selective fibroblast growth factor receptor 2 (FGFR2) inhibitors

doi: 10.1080/14756366.2026.2647526

Figure Lengend Snippet: PLW559 selectively inhibits FGFR2 kinase activity. (A) Selectivity profile of PLW559 against a panel of 76 tyrosine kinases, presented as a heat map; (B) Kinases exhibiting the highest inhibition rates by PLW559 at 1 μM; (C) IC 50 values of PLW559 against FGFR1-4. Pan-FGFR inhibitor TAS120 was included as a positive control and its IC 50 values against FGFR1-4 were 0.793, 0.5634, 0.8203, and 2.724 nM, respectively.

Article Snippet: PLW559 was preincubated with FGFR1, FGFR2, FGFR3 or FGFR4 kinase (Carna Biosciences) and substrate peptide (Peptide30, GL) in 50 mmol/L HEPES, pH 7.5, 10 mmol/L MgCl 2 , 1 mmol/L EGTA, 0.01% Brij-35, 2 mmol/L DTT, and 0.05% BSA for 30 min at room temperature.

Techniques: Activity Assay, Inhibition, Positive Control