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ZT-1a

Names

[ CAS No. ]:
212135-62-1

[ Name ]:
ZT-1a

Biological Activity

[Description]:

ZT-1a is a potent, non-ATP-competitive and selective SPAK inhibitor. ZT-1a inhibits SPAK activity with IC50s of 44.3, 35.0, 46.7 μM at ATP concentrations of 0.01, 0.1 and 1 mM, respectively[1].

[Related Catalog]:

Signaling Pathways >> Others >> Others
Research Areas >> Neurological Disease

[Target]

SPAK[1]


[In Vitro]

ZT-1a inhibits Na-K-2Cl cotransporter (NKCC1) and stimulates K-Cl cotransporters (KCCs) by decreasing their SPS1-related proline/alanine-rich kinase (SPAK)-dependent phosphorylation[1]. ZT-1a inhibits phosphorylation of NKCC1 p-Thr203/207/212 by 72±5.2% at 1 µM ZT-1a and phosphorylation of KCC sites 1/2 by 65-77% at 3 µM in HEK-293 cells[1]. SPAK phosphorylation at Ser373 is inhibited by 70±3.8% inhibition at 3-10 µM ZT-1a[1]. ZT-1a (10 µM) inhibits NKCC1 but stimulates KCC3 activity[1].

[In Vivo]

ZT-1a (10-100 mg/kg) inhibits SPAK-dependent cation-Cl− cotransporters (CCC) phosphorylation in vivo[1]. Animal Model: Naive mice[1] Dosage: 10, 30, 50, and 100 mg/kg Administration: Intraperitoneal (i.p.) administration Result: Inhibited SPAK-dependent cation-Cl- cotransporters (CCC) phosphorylation in vivo.

[References]

[1]. Jinwei Zhang, et al. Modulation of Brain cation-Cl- Cotransport via the SPAK Kinase Inhibitor ZT-1a. Nat Commun. 2020 Jan 7;11(1):78.

Chemical & Physical Properties

[ Molecular Formula ]:
C22H15Cl3N2O2

[ Molecular Weight ]:
445.73


Related Compounds