2. Metabolic Enzyme/Protease
  3. Phosphatase
  4. Z218484536

Z218484536 is a selective and brain-penetrant phosphoserine phosphatase (PSPH) inhibitor. Z218484536 binds to PSPH with a Kd value of approximately 0.23 μM. Z218484536 reduces L-serine and D-serine levels in astrocytes. Z218484536 is able to suppress spontaneous epileptic seizures without causing serious side effects. Z218484536 also shows good anti-epileptic effects in the temporal lobe epilepsy (TLE) model[1].

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Z218484536 Chemical Structure

Z218484536 Chemical Structure

CAS No. : 1223877-07-3

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Description

Z218484536 is a selective and brain-penetrant phosphoserine phosphatase (PSPH) inhibitor. Z218484536 binds to PSPH with a Kd value of approximately 0.23 μM. Z218484536 reduces L-serine and D-serine levels in astrocytes. Z218484536 is able to suppress spontaneous epileptic seizures without causing serious side effects. Z218484536 also shows good anti-epileptic effects in the temporal lobe epilepsy (TLE) model[1].

In Vitro

Z218484536 (40-2,000 nM, 24 h) inhibits the release of l-serine, with an IC50 of 0.4 μM, and reduces cellular L-serine levels with an IC50 of 0.38 μM in cultured astrocytes[1].

Z218484536 (0.078-40 μM, 48 h) no toxic effect on the proliferation of HepG2 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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In Vivo

Z218484536 (0.5-20 mg/kg, i.p., once a day, 3 day) delays the onset of acute epilepsy, reduces the severity of seizures, and is anticonvulsant in a Pentylenetetrazole (PTZ) -induced acute epilepsy model[1].

Z218484536 (2 mg/kg, 4 mg/kg, i.p., once a day 3 day) reduces hippocampal L-serine and D-serine levels in a (kainic acid) KA-induced chronic TLE mouse model[1].

Z218484536 (2 mg/kg, 4 mg/kg, i.p., once a day, 7  weeks) suppresses spontaneous seizures in TLE mice[1].

Z218484536 (4 mg/kg, i.p., once a day, 7 day) not affect the mice's emotional state or motor ability[1].

Z218484536 (1 mg/kg, 2 mg/kg, i.p.,2 weeks, once a day, 3.5 months) reduces epileptic activity in a cynomolgus monkey TLE model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: KA mouse model of chronic TLE[1]
Dosage: 2 mg/kg, 4 mg/kg
Administration: i.p., 7  weeks, once a day
Result: Reduced SES frequency to 0.44  per day .
Not caused weight loss.
Animal Model: PTZ-induced acute model of seizures[1]
Dosage: 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 20 mg/kg
Administration: i.p., 3 days, once a day
Result: Delayed the onset of acute epilepsy The maximum anticonvulsant effect was observed at a concentration of 4 mg kg
Molecular Weight

247.23

Formula

C11H10FN5O
CAS No.
SMILES

O=C(N/N=C/C1=CNN=C1C2=CC=C(F)C=C2)N
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Purity & Documentation
References
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Z218484536 Related Classifications

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Keywords:

Z2184845361223877-07-3Z 218484536Z-218484536PhosphatasePSPHanti-epilepticserineHepG2TLE modelPTZ-induced acute modelInhibitorinhibitorinhibit

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