| Bioactivity | 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]. | ||||||||||||
| Target | SPAK | ||||||||||||
| Invitro | 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: | ||||||||||||
| Name | ZT-1a | ||||||||||||
| CAS | 212135-62-1 | ||||||||||||
| Formula | C22H15Cl3N2O2 | ||||||||||||
| Molar Mass | 445.73 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| 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. |