2. Signaling Pathways
  3. GPCR/G Protein
  4. Hydroxycarboxylic Acid Receptor (HCAR)
  5. HCAR1 Isoform

HCAR1

GPR81; FKSG80; LACR1; lactate receptor 1

Hydroxycarboxylic acid receptor 1 (HCAR1), also known as GPR81, is a G-protein-coupled receptor activated primarily by L-lactate, mediating metabolic sensing and neuroprotective signaling in the central nervous system[1][2][3]. Mechanistically, HCAR1 modulates Gα_i/o and Gα_s pathways without recruiting β-arrestins, linking lactate levels to downstream regulation of cAMP and gene expression in astrocytes and neurons[4][5]. In experimental models, HCAR1 activation promotes axonal development and protects unmyelinated axons and myelin under hypoglycemic conditions, highlighting its role in neural energy homeostasis[6]. Functionally, HCAR1 contributes to epileptic seizure modulation by controlling neuronal excitability, as HCAR1-deficient mice exhibit increased seizure severity and lowered thresholds[7]. In oncology, HCAR1 enhances chemoresistance and survival in cervical cancer cells through up-regulation of ABCB1 transporter and DNA repair proteins, indicating its impact on tumor metabolism and therapy resistance[8][9]. Compared with other hydroxycarboxylic acid receptor isoforms, HCAR1 exhibits a compact ligand-binding pocket stabilized by unique disulfide bonds, conferring selective recognition for lactate versus structurally related metabolites[5]. For experimental applications, selective agonists such as CHBA and AZ7136 and allosteric modulators have been developed, allowing precise probing of HCAR1-mediated pathways in metabolic, neurological, and cancer models[5][4]. These pharmacological tools support both mechanistic studies and the design of interventions targeting metabolic signaling and neuroprotection.

References:

HCAR1 Related Products (5):

Cat. No. Product Name Effect Purity
  • HY-B2227B
    Lactic acid sodium (60% w/w in water)
    		Activator 98.0%
    Lactic acid (DL-Lactic acid) sodium (60% w/w in water) is a hydroxycarboxylic acid receptor 1 (HCAR1) activator and an epigenetic modulator inducing lysine residues lactylation. Lactic acid sodium (60% w/w in water) is a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. Lactic acid sodium (60% w/w in water) is an oncometabolite and has immune protective role of lactate in anti-tumor immunity. Lactic acid sodium (60% w/w in water) also has antimicrobial activity, which can be used as a food preservative.
    This product has a content (w/w) of 60%, and 1 mL of the system contains 798 mg of Lactic acid sodium, i.e., a concentration of 798 mg/mL (i.e., 7.12 M).
  • HY-B2227
    Lactic acid
    		Activator
    Lactic acid (DL-Lactic acid) is a hydroxycarboxylic acid receptor 1 (HCAR1) activator and an epigenetic modulator inducing lysine residues lactylation. Lactic acid is a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. Lactic acid is an oncometabolite and has immune protective role of lactate in anti-tumor immunity. Lactic acid also has antimicrobial activity, which can be used as a food preservative.
  • HY-W016868
    3-Chloro-5-hydroxybenzoic acid
    		Agonist 99.54%
    3-Chloro-5-hydroxybenzoic acid is a potent, orally active and selective lactate receptor GPR81 agonist, with an EC50 of 16 μM for human GPR81. 3-Chloro-5-hydroxybenzoic acid exhibits favorable in vivo effects on lipolysis in a mouse model of obesity.
  • HY-W015560
    3,5-Dihydroxybenzoic acid
    		Agonist 99.98%
    3,5-Dihydroxybenzoic acid a potential biomarker for the consumption of many food products, including beer, nuts, peanut, and pulses. 3,5-Dihydroxybenzoic acid is the agonist for hydroxycarboxylic acid receptor 1 (HCA1, also known as GPR81) that inhibits lipolysis in adipocytes. 3,5-Dihydroxybenzoic acid is the competitive inhibitor for tyrosine phenol-lyase (TPL), exhibits an affinity of Ki=25.7 μM. 3,5-Dihydroxybenzoic acid is orally active.
  • HY-B2227A
    Lactic acid calcium
    		Activator 98.5%
    Lactic acid (DL-Lactic acid) calcium is a hydroxycarboxylic acid receptor 1 (HCAR1) activator and an epigenetic modulator inducing lysine residues lactylation. Lactic acid calcium is a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. Lactic acid calcium is an oncometabolite and has immune protective role of lactate in anti-tumor immunity. Lactic acid calcium also has antimicrobial activity, which can be used as a food preservative.