GPR34 receptor antagonist 3

GPR34 receptor antagonist 3 (Compound 5e) is a class of GRP34 antagonists, IC50 is 0.680 μM. GPR34 receptor antagonist 3 inhibited ERK1/2 phosphorylation induced by lysophosphatidylserine in a dose-dependent way without obvious cytotoxicity. GPR34 receptor antagonist 3 shows antisensory activity in mouse neuropathic pain model .

GPR34 receptor antagonist 3 (30 μM, 72 h) in HEK293T, COS-7, BEAS-2B, Muller, LX-2 and HUVEC cells do not show obvious cytotoxicity against these cell lines with IC₅₀ > 30 μM^[1].
GPR34 receptor antagonist 3 (3, 10 and 30 μM, 72 h) dose-dependently inhibited the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) induced by LysoPS in CHO cells expressing GPR34^[1].

GPR34 receptor antagonist 3 (200 mg/kg, Intraperitoneal injection, twice a day) observes the death of C57BL/6J mice in the acute toxicity experiment, GPR34 receptor antagonist 3 (100 mg/kg, Intraperitoneal injection, twice a day) mice has no damage during repeated toxicity experiment, and the dose was safe ^[1].
GPR34 receptor antagonist 3 (10 or 20 mg/kg, Intraperitoneal injection,twice a day) can significantly reduce mechanical pain in a mouse neuropathic pain model ^[1].

References:
[1]. Zhou P et al. Discovery of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists. Bioorg Med Chem Lett. 2023 Nov 8:129548.