UNC9994, an analog of Aripiprazole, is a functionally selective β-arrestin-biased dopamine D2 receptor (D2R) agonist withEC₅₀<10 nm for β-arrestin-2 recruitment to d2 receptors. unc9994 is simultaneously partial agonists of translocation and antagonists g_i-regulated cAMP production. Antipsychotic Activity^[1].

UNC9994 displays a lower binding affinity (K_i=79 nM) to D2R than UNC9975, UNC0006, and aripiprazole. At serotonin (as known as 5-HT) receptors, UNC9994 displays moderate to high binding affinities (K_i=25-512 nM) for 5HT_2A, 5HT_2B, 5HT_2C, and 5HT_1A, but is significantly less potent in functional assays (Ca²⁺mobilization FLIPR or cAMP biosensor). UNC9994 is an antagonist at 5HT_2Aand 5HT_2Band agonists at 5HT_2Cand 5HT_1A. UNC9994 has relatively high affinities to H₁-histamine receptor (K_i=2.4 nM) but is less potent antagonists in H₁functional assays^[1].

The antipsychotic-like activity displayed by UNC9994 (2 mg/kg; i.p.) in wild-type mice is completely abolished in β-arrestin-2 knockout mice^[1].

421.38

C₂₁H₂₂Cl₂N₂OS

1354030-51-5

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