UNC9994 

UNC9994, an analog of Aripiprazole, is a functionally selective β-arrestin-biased dopamine D2 receptor (D2R) agonist with EC₅₀ <10 nM for β-arrestin-2 recruitment to D2 receptors. UNC9994 is simultaneously partial agonists of β-arrestin-2 translocation and antagonists of 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_2A and 5HT_2B and agonists at 5HT_2C and 5HT_1A. UNC9994 has relatively high affinities to H₁-histamine receptor (K_i=2.4 nM) but is less potent antagonists in H₁ functional assays^[1].

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

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].

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

421.38

C₂₁H₂₂Cl₂N₂OS

1354030-51-5

Solid

White to off-white

ClC1=CC=CC(C2CCN(CC2)CCCOC3=CC4=C(C=C3)SC=N4)=C1Cl

Room temperature in continental US; may vary elsewhere.

• [1]. Allen JA, et al. Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc Natl Acad Sci U S A. 2011;108(45):18488-18493.  [Content Brief]