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Biological Activity:

INDY is a potent and selective DYRK1A/B inhibitor with IC50 of 0.23 and 0.24 μM for DYRK1B and DYRK1A respectively. It binds at the ATP-binding cleft of the enzyme, and reverses aberrant tau-phosphorylation and rescues repressed calcineurin/NFAT signaling. INDY can impair the self-renewal capacity of subventricular zone neural stem cells. INDY can also induce regeneration and expansion of both rat and ***** human beta cells in vivo or ex vivo, and the nuclear factors of activated T cells (NFAT) family of transcription factors are defined as likely mediators of human beta cell proliferation and differentiation.

How to Use:

In vitro: INDY was used at 10-15 µM final concentration in various in vitro assays.
In vivo: n/a

Reference:

• 1. Ogawa Y, et al. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. (2010) Nat Commun. 1:86.
• 2. Pozo N, et al. Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth. (2013) J Clin Invest. 123(6):2475-87.
• 3. Wang P, at al. A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. (2015) Nat Med. In press.