Tyrosine kinase-IN-1

Tyrosine kinase-IN-1 is a multi-targeted tyrosine kinase inhibitor with IC50s of 4, 20, 4, 2 nM for KDR, Flt-1, FGFR1 and PDGFRα, respectively.

Research Areas >> Cardiovascular Disease

Flt-1:4 nM (IC50)

KDR:20 nM (IC50)

PDGFRα:4 nM (IC50)

FGFR1:2 nM (IC50)

Tyrosine kinase-IN-1 is from reference (compound 8K)[1].

Tyrosine kinase-IN-1 shows a reasonable PK profile (AUC(0–∞)=1.9, t1/2=4.6 h). It has a favorable oral bioavailability (F=63%) in rats[1].

Kinase Inhibition Assays Kinase activities of KDR and PDGFRα are measured as the percent of ATP consumed following the kinase reaction using luciferaseluciferin-coupled chemiluminescence. Kinase reactions are initiated by combining test compound (Tyrosine kinase-IN-1), ATP, kinases and substrates in a 20 mL volume using 384-well microtiter plates. For KDR, the final reaction mixture contained 3 mM ATP, 1.6 mM poly(Glu, Tyr) 4:1 and 1.5 nM KDR of residues D807-V1356 with an N-terminal GST tag. For PDGFRα, the final reaction mixture contained 2 mM ATP, 10 mM MBP and 14 nM PDGFRα of residues Q551-L1089 with an N-terminal GST tag. The reaction mixture is incubated at room temperature for 4 h (KDR) or 2 h PDGFRα before a 20 mL aliquot of Kinase Glo is added and luminescence signal is measured using a Victor2 plate reader. Total ATP consumption is limited below 50%[1].

[1]. Moon K, et al. The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorganic & Medicinal Chemistry Letters 22 (2012) 4979–4985

Nintedanib (BIBF 1120) | Infigratinib (BGJ398) | SU5416 | AZD4547 | Apatinib Mesylate | Crenolanib | PD173074 | Foretinib (GSK1363089) | Erdafitinib(JNJ-42756493) | FGF-401 | SU 5402 | Linifanib (ABT-869) | Heparan Sulfate | Cediranib | Lucitanib