1. Signaling Pathways
  2. GPCR/G Protein
  3. Hydroxycarboxylic Acid Receptor (HCAR)

Hydroxycarboxylic Acid Receptor (HCAR) (羟基羧酸受体)

羟基羧酸 (HCA) 受体家族由三个成员组成,即 HCA1、HCA2 和 HCA3,又分别称为 GPR81、GPR109A 和 GPR109B,它们由密切相关的基因编码。HCA 受体的生理配体是关键的代谢中间体,其局部和系统水平反映特定的代谢状态。糖酵解的最终产物乳酸可激活 HCA1,而酮体 3-羟基丁酸 [b-羟基丁酸盐 (b-HB)] 和 b-氧化中间体 3-羟基辛酸分别可激活 HCA2 和 HCA3。此外,HCA2 也可由丁酸激活。所有这三种 HCA 受体在白色和棕色脂肪细胞中均有高度表达。研究表明,在脂肪细胞从前脂肪细胞分化过程中以及过氧化物酶体增殖激活受体-γ 激活后,HCA1 和 HCA2 的表达会增加。高脂饮食 (HFD) 喂养和暴露于各种炎症刺激都会导致脂肪组织中 HCA1 表达减少。虽然 HFD 喂养后脂肪组织中的 HCA2 表达也会减少,但炎症刺激会增加 HCA2 的表达。在过去十年中,人们已经清楚地认识到 HCA 受体通过控制代谢、免疫和其他身体功能,有助于在不断变化的代谢和饮食条件下维持体内平衡。此外,基于 HCA 受体的遗传小鼠模型和合成配体的研究还表明,该受体家族的成员可以作为预防和治疗代谢和炎症等疾病的靶点。

The hydroxycarboxylic acid (HCA) receptor family consists of three members, HCA1, HCA2, and HCA3, also known as GPR81, GPR109A, and GPR109B, respectively, which are encoded by closely related genes. The physiological ligands of HCA receptors are key metabolic intermediates whose local and systemic levels reflect particular metabolic states. Lactic acid, the end product of glycolysis, activates HCA1, whereas the ketone body 3-hydroxy-butyric acid [b-hydroxybutyrate (b-HB)] and the b-oxidation intermediate 3-hydroxy-octanoic acid activate HCA2 and HCA3, respectively. In addition, HCA2 is also activated by butyric acid. All three HCA receptors are highly expressed in white and brown adipocytes. Expressions of HCA1 and HCA2 have been shown to increase during differentiation of adipocytes from preadipocytes as well as after activation of peroxisome proliferator-activated receptor-gamma. Both high-fat diet (HFD) feeding and exposure to various inflammatory stimuli result in decreased expression of HCA1 in the adipose tissue. While HCA2 expression in the adipose tissue is also decreased after HFD feeding, inflammatory stimuli increase expression of HCA2. During the past decade, it has become clear that HCA receptors help to maintain homeostasis under changing metabolic and dietary conditions, by controlling metabolic, immune, and other body functions. Work based on genetic mouse models and synthetic ligands of HCA receptors has, in addition, shown that members of this receptor family can serve as targets for the prevention and therapy of diseases such as metabolic and inflammatory disorders.

Hydroxycarboxylic Acid Receptor (HCAR) 相关产品 (5):

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-135982
    GPR81 agonist 1 Inhibitor 99.73%
    GPR81 agonist 1 是一种高效、高选择性的 GPR81 激动剂,对人和小鼠 GPR81 的EC50 分别为 58 nM 和 50 nM。GPR81 agonist 1 抑制分化的 3T3-L1 脂肪细胞的脂解。GPR81 agonist 1 抑制小鼠的脂解并不会造成皮肤潮红。GPR81 agonist 1 对 GPR81 的选择性高于 GPR109a
    GPR81 agonist 1
  • HY-W016868
    3-Chloro-5-hydroxybenzoic acid

    3-氯-5-羟基苯甲酸

    Agonist 99.54%
    3-Chloro-5-hydroxybenzoic acid 是一种有效的、具有口服活性的,选择性乳酸受体 GPR81 激动剂,对人 GPR81 的 EC50 为 16 μM。3-Chloro-5-hydroxybenzoic acid 在肥胖小鼠模型中显示出良好的体内脂肪分解作用。
    3-Chloro-5-hydroxybenzoic acid
  • HY-100976
    LUF6283 Agonist ≥99.0%
    LUF6283 是一种口服有效的 HCA(2) 部分激动剂,其 Ki 为 0.55 μM。LUF6283 既能达到烟酸有益的降脂作用,又不会产生皮肤潮红的副作用。
    LUF6283
  • HY-141434
    5-OxoETE methyl ester Agonist
    5-OxoETE methyl ester 是氧代二十烷酸受体 (oxoeicosanoid receptor 1OXER1)的激动剂。5-OxoETE methyl ester 与 OXER1 结合,并激活下游信号通路 β-arrestin 募集 (β-arrestin recruitment),EC50 为 1.54 µM。
    5-OxoETE methyl ester
  • HY-148563
    GPR81 agonist 2 Inhibitor
    GPR81 agonist 2 (compound 1) 是一种有效的 GPR81 激动剂,对于 hGPR81、hGPR109A 的 EC50 值分别为 0.023、0.123 µM。
    GPR81 agonist 2