P2Y14 Receptor Antagonist

PPTN, a chemical probe, is a potent, high-affinity, competitive and highly selective P2Y14 receptor antagonist with a K_B value of 434 pM. PPTN exhibits no agonist or antagonist effect at the P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, or P2Y13 receptors. Anti-inflammatory and immune activity.

P2Y14R antagonist 2 (compound 39) is a potent, selective and orally active P2Y14R antagonist with an IC₅₀ value of 0.40 nM. P2Y14R antagonist 2 shows anti-inflammatory activity. P2Y14R antagonist 2 has the potential for the research of colitis.

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.

HDL-16 is a potent P2Y₁₄R antagonist with an IC₅₀ of 0.3095 nM. HDL-16 ameliorates DSS (HY-116282C)-induced colitis through suppressing necroptosis of intestinal epithelium cells (IECs) and protecting mucosal barrier function.

MRS4917 is an orally active, potent selective P2Y₁₄ receptor (hP2Y₁₄R) antagonist (IC₅₀ = 2.88 nM, K_i = 1.67 nM) that shows >18,000 fold selectivity against P2Y₆R (IC50 = 54 μM). MRS4917 demonstrates oral efficacy in reversing established mechanoallodynia in the chronic constriction injury (CCI) mouse model, while having no effect on thermoregulation. MRS4917 can be used for neurological diseases research.

MRS4833 (compound 15) is an orally active, potent, competitive P2Y₁₄R antagonist with an of IC₅₀ of 5.92 nM for hP2Y₁₄R and an IC₅₀ of 4.8 nM for mP2Y₁₄R. MRS4833 reduces airway eosinophilia in a protease-mediated asthma model and reverses chronic neuropathic pain in a mouse CCI model.

MRS4608 (Compound 17) is a selective P2Y14 receptor antagonist with IC₅₀ values of 20 (hP2Y14R) and 21.4 nM (mP2Y14R). MRS4608 has anti-inflammatory activity and can reduce the infiltration of eosinophils. MRS4608 can be used for the researches of inflammation and immunology, such as asthma.

P2Y14R antagonist 3 (Compound A) is a potent and orally active P2Y₁₄R antagonist with an IC₅₀ value of 23.60 nM and a K_d value of 7.26 μM. P2Y14R antagonist 3 can reduce the degree of lung injury in the Lipopolysaccharides (LPS) (HY-D1056)-induced acute lung injury mice. P2Y14R antagonist 3 can be used for inflammatory diseases.

P2Y₁₄R antagonist 4 (Compound 25l) is an orally active P2Y₁₄R antagonist (IC₅₀: 5.6 nM) with superior binding affinity to P2Y₁₄R over PPTN. P2Y₁₄R antagonist 4 has anti-inflammatory activity and reduces LPS (HY-D1056)-induced proinflammatory cytokines (IL-1β, IL-6, and TNF-α) release.