INDY

INDY is a potent and ATP-competitive Dyrk1A and Dyrk1B inhibitor with IC50s of 0.24 μM and 0.23 μM, respectively. INDY binds in the ATP pocket of the enzyme and has a Ki value of 0.18 μM for Dyrk1A. INDY sharply reduces the self-renewal capacity of normal and tumorigenic cells in primary Glioblastoma (GBM) cell lines and neural progenitor cells[1][2].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> DYRK

IC50: 0.24 μM (Dyrk1A) and 0.23 μM (Dyrk1B)[1] Ki: 0.18 μM (Dyrk1A)[1]

INDY (0.3-30 μM; 20 hours) mildly inhibits tau-phosphorylation at 3 μM, and nearly completely inhibits at 30 μM[1]. INDY effectively reverses the aberrant tau-phosphorylation and rescues the repressed NFAT (nuclear factor of activated T cell) signalling induced by Dyrk1A (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A) overexpression[1]. Western Blot Analysis[1] Cell Line: COS7 cells transfected with either EGFP-Dyrk1A and EGFP-tau Concentration: 0.3, 1, 3, 10, 30 μM Incubation Time: 20 hours Result: Mildly inhibited tau-phosphorylation at 3 μM, and nearly completely inhibited at 30 μM.

ProINDY (2.5 μM) recoveres apparently normal development of the Xenopus embryo[1].

[1]. Ogawa Y, et al. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun. 2010 Oct 5;1:86.

[2]. Pozo N, et al. Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastomagrowth. J Clin Invest. 2013 Jun;123(6):2475-87.