P2Y receptors (P2YRs) are a family of G protein-coupled receptors activated by extracellular nucleotides. Physiological P2YR agonists include purine and pyrimidine nucleoside di- and triphosphates, such as ATP, ADP, UTP, UDP, nucleotide sugars, and dinucleotides. Eight subtypes exist, P2Y₁, P2Y₂, P2Y₄, P2Y₆, P2Y₁₁, P2Y₁₂, P2Y₁₃, and P2Y₁₄, which represent current or potential future drug targets. Here we provide a comprehensive overview of ligands for the subgroup of the P2YR family that is activated by uracil nucleotides: P2Y₂ (UTP, also ATP and dinucleotides), P2Y₄ (UTP), P2Y₆ (UDP), and P2Y₁₄ (UDP, UDP-glucose, UDP-galactose). The physiological agonists are metabolically unstable due to their fast hydrolysis by ectonucleotidases. A number of agonists with increased potency, subtype-selectivity and/or enzymatic stability have been developed in recent years. Useful P2Y₂R agonists include MRS2698 (6-01, highly selective) and PSB-1114 (6-05, increased metabolic stability). A potent and selective P2Y₂R antagonist is AR-C118925 (10-01). For studies of the P2Y₄R, MRS4062 (3-15) may be used as a selective agonist, while PSB-16133 (10-06) is a selective antagonist. Several potent P2Y₆R agonists have been developed including 5-methoxyuridine 5′-O-((R_p)α-boranodiphosphate) (6-12), PSB-0474 (3-11), and MRS2693 (3-26). The isocyanate MRS2578 (10-08) is used as a selective P2Y₆R antagonist, although its reactivity and low water-solubility are limiting. With MRS2905 (6-08), a potent and metabolically stable P2Y₁₄R agonist is available, while PPTN (10-14) represents a potent and selective P2Y₁₄R antagonist. The radioligand [³H]UDP can be used to label P2Y₁₄Rs. In addition, several fluorescent probes have been developed. Uracil nucleotide-activated P2YRs show great potential as drug targets, especially in inflammation, cancer, cardiovascular and neurodegenerative diseases.

P2Y受体（P2YRs）是由细胞外核苷酸激活的G蛋白偶联受体家族。生理学上的P2YR激动剂包括嘌呤和嘧啶核苷二磷酸和三磷酸，例如ATP，ADP，UTP，UDP，核苷酸糖和二核苷酸。存在八个亚型，P2Y ₁，P2Y ₂，P2Y ₄，P2Y ₆，P2Y ₁₁，P2Y ₁₂，P2Y ₁₃和P2Y ₁₄，它们代表当前或潜在的未来药物靶标。在这里，我们提供了由尿嘧啶核苷酸激活的P2YR家族亚基配体的全面概述：P2Y ₂（UTP，也是ATP和二核苷酸），P2Y ₄（UTP），P2Y₆（UDP）和P2Y ₁₄（UDP，UDP-葡萄糖，UDP-半乳糖）。生理激动剂由于其被外切核苷酸酶快速水解而在代谢上不稳定。近年来，已经开发了许多具有增强的效力，亚型选择性和/或酶稳定性的激动剂。有用P2Y ₂ - [R激动剂包括MRS2698（6 - 01，高选择性）和PSB-1114（6 - 05，增加的代谢稳定性）。有效和选择性P2Y ₂ - [R拮抗剂是AR-C118925（10 - 01）。对于P2Y研究₄ R，MRS4062（3 - 15）可以被用作选择性激动剂，而PSB-16133（10 - 06）是一种选择性的拮抗剂。几种强效的P2Y ₆ - [R激动剂已经被开发，包括5-methoxyuridine 5'- ø - （（[R _p）α-boranodiphosphate）（6 - 12），PSB-0474（3 - 11），和MRS2693（3 - 26）。异氰酸酯MRS2578（10 - 08）被用作一种选择性P2Y ₆ - [R拮抗剂，虽然它的反应性和低的水溶解度限制。随着MRS2905（6 - 08），一种有效的和代谢稳定的P2Y ₁₄ R激动剂是可用的，而人民邮电报（10 - 14）代表一个有效的和选择性P2Y ₁₄ - [R拮抗剂。放射性配体[ ³ H] UDP可用于标记P2Y ₁₄ Rs。另外，已经开发了几种荧光探针。尿嘧啶核苷酸激活的P2YRs具有作为药物靶标的巨大潜力，尤其是在炎症，癌症，心血管疾病和神经退行性疾病中。