AC-263093 (free base)

AC-263093 free base (AC-093) is a NPFFR2 agonist and a NPFFR1 functional antagonist, with pKi values of 6.9 and 7.0, respectively. AC-263093 free base selectively activates NPFFR2 (and inhibits NPFFR1) coupled to Gai/o proteins, thereby inhibiting adenylyl cyclase to reduce cAMP production. AC-263093 free base can be used for research on depression and anxiety-like disorders, inflammatory and neuropathic pain, and opioid tolerance^{[1][2][3][4][5]}. In Vitro:AC-263093 (AC-093 hydrochloride) (1 μM; 15 min) inhibits Forskolin (HY-15371)-stimulated cAMP production in mRPTCs (mouse renal proximal tubule cells)^[1].
AC-263093 (0.1 μM; 30 min) attenuates the stimulation of intracellular cAMP concentration by Fenoldopam (HY-B0735A) in hRPTCs (human renal proximal tubule cells)[1].

AC-263093 binds to human NPFFR2 and NPFFR1 with K_i values of 1296 nM and 3320 nM, respectively, and in a cAMP functional assay, it has a pEC₅₀ of 5.2 for NPFFR2 with an efficacy of 78%^[3].
AC-263093 is a full agonist of the recombinant human FF2 receptor in NIH-3T3 cells with a pEC₅₀ of 5.9, and shows very low intrinsic efficacy at the human FF1 receptor (12% at 6 μM)^[3].

AC-263093 has full efficacy at recombinant human FF2 receptors in HEK-293T cells, with a pEC₅₀ of 5.2, and shows only weak agonist activity at human FF1 receptors (23% at 30 μM)^[3].
AC-263093 binds human NPFFR1 and NPFFR2 with approximately equal affinity in radioligand binding assays (pK_i = 7.0 and 6.9, respectively)^[5].
AC-263093 (5 µM) functionally inhibits NPFFR1 in NIH/3T3 cells transfected with NPFFR1, completely abolishing 1 µM NPAF-induced β-galactosidase activity^[5]. In Vivo:AC-263093 (AC-093 hydrochloride) (30 mg/kg; i.p.; single administration; 1 h before behavioral testing) significantly upregulated blood corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels in a wild-type C57BL/6 mouse model^[2].
AC-263093 (20 mg/kg; i.p.; once daily; 20 days) increased immobility time in the tail suspension test, induced anhedonic responses to sucrose, elicited anxiety-like behavior in the elevated plus maze, and decreased hippocampal GR and MR protein levels in wild-type C57BL/6 mouse models^[2].
AC-263093 (10 mg/kg; i.p.; single administration; 15 min before formalin injection) selectively reduces formalin-induced phase 2 flinching behavior in rats^[3].
AC-263093 (1-10 mg/kg; i.p.; single administration) dose- and time-dependently attenuated thermal hyperalgesia in the Carrageenan (HY-125474)-induced inflammatory thermal hyperalgesia model in SD rats^[3].
AC-263093 (1-30 mg/kg; i.p.; single administration) dose-dependently reversed SNL-induced mechanical hypersensitivity in rats^[3].