ZT-1a

• CAT Number: I015178
• CAS Number: 212135-62-1
• Molecular Formula: C22H15Cl3N2O2
• Molecular Weight: 445.73
• Purity: ≥95%
• Synonyms: 5-chloro-N-[5-chloro-4-[(4-chlorophenyl)-cyanomethyl]-2-methylphenyl]-2-hydroxybenzamide
• InChI: InChI=1S/C22H15Cl3N2O2/c1-12-8-16(18(11-26)13-2-4-14(23)5-3-13)19(25)10-20(12)27-22(29)17-9-15(24)6-7-21(17)28/h2-10,18,28H,1H3,(H,27,29)
• InChIKey: RPTKRVXJNWPJLU-UHFFFAOYSA-N
• SMILES: CC1=CC(=C(C=C1NC(=O)C2=C(C=CC(=C2)Cl)O)Cl)C(C#N)C3=CC=C(C=C3)Cl

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].
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].
ZT-1a (10-100 mg/kg) inhibits SPAK-dependent cation-Cl− cotransporters (CCC) phosphorylation in vivo[1].

Reference

[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.
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