ZT-1a | SPAK kinase inhibitor

CAS:
 212135-62-1
Catalog Number:
 10-4402
ZT-1a chemical structure

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ZT-1a (212135-62-1) is a non-ATP competitive inhibitor (IC50 = 44.3 µM @ 0.01 mM ATP) of SPAK kinase (STK39), a master regulator of cation-Cl– cotransporters.1 It attenuated cerebral edema, protected against ischemic brain damage, and improved post-ischemic neurological outcomes in mouse models of stroke.1,2 ZT-1a showed neuroprotective effects in mouse models of vascular dementia3 and multiple sclerosis4.  It inhibited the progression of hepatocellular carcinoma in rodent models and showed synergistic effects with PD-1 antibodies by helping to prevent tumor microenvironment immune exhaustion.5

References/Citations:

  1. Zhang et al. (2020), Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a; Nat. Commun. 11 78
  2. Wang et al. (2022), Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke; J. Neuroinflammation 19 91
  3. Bhuiyan et al. (2024), SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia; CNS Neurosci. Ther. 30 e14654
  4. Qi et al. (2025), Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis; J. Neuroinflammation 22 80
  5. Pan et al. (2026), Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma; Nat. Commun. 17 1414
212135-62-1, SPAK inhibitor, SPAK kinase inhibitor, STK39 inhibitor, ZT-1a, ZT-1a supplier, ZT1a
CAS:
212135-62-1
Catalog Number:
10-4402
Activity:
SPAK kinase inhibitor
Chemical Names:
5-Chloro-N-[5-chloro-4-[(4-chlorophenyl)-cyanomethyl]-2-methylphenyl]-2-hydroxybenzamide
Molecular Weight:
445.72
Molecular Formula:

C22H15Cl3N2O2

Solubility:
Soluble in DMSO (>25 mg/ml)
Physical Properties:
Off-white solid
Purity:

>98% HPLC
NMR: (Conforms)

Storage Temperature:
-20°C
Stability:
Stable for up to 2 years when stored as supplied @ -20°C. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
Shipping Code:
RT

Safety Data Sheet:

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Product Data Sheet:

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ZT-1a (212135-62-1) is a non-ATP competitive inhibitor (IC50 = 44.3 µM @ 0.01 mM ATP) of SPAK kinase (STK39), a master regulator of cation-Cl– cotransporters.1 It attenuated cerebral edema, protected against ischemic brain damage, and improved post-ischemic neurological outcomes in mouse models of stroke.1,2 ZT-1a showed neuroprotective effects in mouse models of vascular dementia3 and multiple sclerosis4.  It inhibited the progression of hepatocellular carcinoma in rodent models and showed synergistic effects with PD-1 antibodies by helping to prevent tumor microenvironment immune exhaustion.5

References/Citations:

  1. Zhang et al. (2020), Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a; Nat. Commun. 11 78
  2. Wang et al. (2022), Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke; J. Neuroinflammation 19 91
  3. Bhuiyan et al. (2024), SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia; CNS Neurosci. Ther. 30 e14654
  4. Qi et al. (2025), Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis; J. Neuroinflammation 22 80
  5. Pan et al. (2026), Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma; Nat. Commun. 17 1414

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