GSK-114

Biological Activity

GSK-114 is a highly selective, orally active TNNI3K inhibitor (IC50= 25 nM). GSK-114 shows a 40-fold selectivity for TNNI3K over B-Raf kinase (IC50= 1 μM). Cardiac troponin I-interacting kinase (TNNI3K or CARK) is a member of the tyrosine-like kinase family that is selectively expressed in heart tissue[1]. At a concentration of 1 μM, GSK114 demonstrated an affinity for seven other kinases: ACK1, B-Raf, GAK, MEK5, PDGFRB, STK36, and ZAK[2]. GSK-114 affords the best balance of specificity and pharmacokinetics, demonstrating useful oral exposure (poDNAUC=0.18, Cmax=130 ng/ml @ 2 mg/kg, t1/2=3.6 hr, rat Fu=20.2%)[1].

References

[1]. Lawhorn BG, et al. GSK114: A selective inhibitor for elucidating the biological role of TNNI3K. Bioorg Med Chem Lett. 2016;26(14):3355-3358. [2]. Asquith CRM, et al. New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I-Interacting Kinase (TNNi3K). Molecules. 2020;25(7):1697. Published 2020 Apr 7.