| Chemical Properties | Back Directory | [Boiling point ]
684.8±40.0 °C(predicted) | [density ]
1.627±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [pka]
12.30±0.30(predicted) |
| Hazard Information | Back Directory | [Uses]
P2Y14R antagonist 1 (compound I-17) is a selective P2Y14R antagonist with an IC50 of 0.6 nM. It exhibits potent P2Y14R antagonistic activity, both in vitro and in vivo efficacy, and favorable pharmacokinetic profiles. P2Y14R antagonist 1 reduces the release of inflammatory factors and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. P2Y14R antagonist 1 holds promise for research in the field of acute gouty arthritis[1]. | [in vivo]
P2Y14R antagonist 1 (compound I-17) (5-20 mg/mL, i.p., 1 h) can promote the inflammatory response caused by MSU crystal injection-induced acute gouty arthritis in the MSU-induced mouse gout model[1].
1.19 Pharmacokinetic Analysis in MC38 Syngeneic Model[1]|
| P2Y14R antagonist 1 | Cmax(g/mL) | T1/2 (h) | Tmax (h) | AUC0-∞ (h ng/mL) | CL (L/h/kg) | F (%) | | i.v. (10 mg/kg) | 1533 | 7.6 | 18 | 1765 | 3.5 | | | p.o. (30 mg/kg) | 2895 | 12.60 | 32 | 2845 | 14.80 | 75 |
| Animal Model: | Acute gouty arthritis model[1] | | Dosage: | 5-20 mg/mL | | Administration: | Intraperitoneal injection (i.p.) , Injection time: 60 min | | Result: | Effectively reduced paw swelling in the MSU-induced mouse gout model, significantly decreased the production of pro-inflammatory cytokines IL-1β, IL-6, and IL-18 induced by MSU, markedly inhibited inflammatory cell infiltration in foot tissues induced by MSU, and significantly suppressed the increase of NLRP3 induced by MSU. |
| [IC 50]
P2Y14 Receptor: 0.6 nM (IC50); P2Y2 Receptor: > 100 nM (IC50); P2Y6 Receptor: 89.7 nM (IC50); P2Y12 Receptor: > 100 nM (IC50); P2Y1 Receptor: > 100 nM (IC50); NLRP3 | [References]
[1] Liu W, et al. Discovery of N-Substituted Acetamide Derivatives as Promising P2Y14R Antagonists Using Molecular Hybridization Based on Crystallographic Overlay. J Med Chem. 2024 Jun 27;67(12):10233-10247. DOI:10.1021/acs.jmedchem.4c00555 |
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