TPH2 agonist-1 

TPH2 agonist-1 (compound 20e) is an orally active, blood-brain barrier permeable, 1,3,4-oxadiazol-2 (3H)-one-derived TPH2 agonist. TPH2 agonist-1 upregulates TPH2 expression, elevates 5-HT and GABA levels, and exhibits antiepileptic activity in SCN1A-deficient models. TPH2 agonist-1 stabilizes the electrophysiological activity of neuronal networks and inhibits abnormal spike and burst activities. TPH2 agonist-1 shows no significant hERG inhibition or cytotoxicity, and it can be used in studies related to severe myoclonic epilepsy of infancy (Dravet syndrome)^[1].

TPH2 agonist-1 (compound 20e) dose-dependently inhibits the abnormal electrophysiological activity of iPSC-derived neurons from SMEI patients. At 1 μM, it significantly reduces the average firing rate and burst percentage, while at 10 μM and 50 μM, it further decreases the network burst frequency and duration^[1].
Treatment of wild-type (WT) and scn1lab KO zebrafish larvae with TPH2 agonist-1 (5 μM; 4 h) increases the levels of serotonin (5-HT) and γ-aminobutyric acid (GABA), and restores 5-HT immunoreactivity in the hypothalamus of KO larvae^[1].

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

TPH2 agonist-1 (compound 20e) exhibits brain-to-plasma (B/P) ratios of 4.36, 1.75, and 0.43 in mouse models, adult zebrafish models, and the human blood-brain barrier (BBB) system, respectively^[1].
TPH2 agonist-1 (5 mg/kg; administered via oral gavage; single dose; heat induction performed 30 min post-administration) significantly reduces seizure severity, prolongs the latency to the first seizure, increases the seizure threshold temperature, and inhibits hyperactivity in SCN1A^+/- mice, with no effect on the behaviors of wild-type mice^[1].
TPH2 agonist-1 (2.5 μM, 5 μM; waterborne exposure; single exposure; recording performed 30 min post-exposure) dose-dependently reduces seizure-like locomotion in scn1lab KO zebrafish larvae, with a 41.58% reduction at 2.5 μM and a 16.3% reduction at 5 μM. It does not affect the normal locomotion of wild-type zebrafish and can also restore the blue color preference of KO larvae^[1].

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

373.69

C₁₅H₈ClF₄N₃O₂

FC(C=C1)=CC(Cl)=C1CN2C(OC(C3=CC(C(F)(F)F)=NC=C3)=N2)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Kim DG, et al. Development of Novel Small-Molecule Targeting SCN1A-Associated Severe Myoclonic Epilepsy of Infancy. J Med Chem. 2026;69(3):3362-3377.  [Content Brief]