Target intelligence / Profile preview

P2Y purinoceptor 13 (P2RY13)

Target
P2RY13
Molecular classification
G protein-coupled receptor, Family A G protein-coupled receptor, Purinergic receptor, Membrane receptor
01

Overview

P2Y purinoceptor 13 (P2RY13) is a G protein-coupled receptor (GPCR) primarily activated by adenosine diphosphate (ADP) and coupled to the Gi signaling pathway [1, 7, 8]. It is widely expressed in the liver, brain, bone marrow, and immune cells, where it plays a critical role in regulating diverse physiological processes such as lipid metabolism, bone homeostasis, and neuroprotection [2, 4, 11]. In the liver, P2RY13 activation promotes reverse cholesterol transport by enhancing the uptake of high-density lipoprotein (HDL)-derived cholesterol, making it a potential target for treating atherosclerosis and hypercholesterolemia [4, 6]. In the skeletal system, it modulates the balance between osteoblast and adipocyte differentiation, and its inhibition has been suggested as a strategy to enhance bone formation in osteoporosis [6, 15]. Furthermore, P2RY13 signaling is involved in protecting neurons from oxidative stress and excitotoxicity, suggesting therapeutic potential in neurodegenerative diseases [4, 13]. While several P2Y12 antagonists like cangrelor show cross-reactivity with P2RY13, the development of selective modulators remains an active area of research to minimize off-target effects and harness its tissue-specific benefits [11, 12].

Other names
P2Y13Purinergic receptor P2Y13G-protein coupled receptor 86 (GPR86)G-protein coupled receptor 94 (GPR94)FKSG77GPCR1SP174
02

Mechanism of action

Agonism or antagonism of the Gi-coupled purinergic signaling pathway, which inhibits adenylate cyclase and reduces intracellular cAMP levels to modulate metabolic and protective cellular responses [4, 11, 12].

03

Biological functions

Signal transduction [1, 8]Lipid metabolism (Reverse cholesterol transport) [4, 6]Bone homeostasis (Osteoblast/adipocyte balance) [6, 15]Neuroprotection [11, 13]Immune response modulation [2, 7]Glucose metabolism (Hepatic gluconeogenesis) [5, 11]Hematopoiesis [2, 7]
04

Disease associations

Cardiovascular disease (Atherosclerosis, Hypercholesterolemia) [4, 6]Osteoporosis [6, 15]Diabetes and Metabolic syndrome [5, 6]Neurodegenerative disease (Alzheimer's disease) [4, 11]Inflammation (Asthma) [6]Pain transmission [11]
05

Safety considerations

Potential bleeding risk due to cross-reactivity with P2Y12 receptors [11, 12]Risk of worsening insulin resistance or fatty liver disease upon systemic inhibition [6]Tissue-specific side effects due to broad expression in brain, liver, and bone [4, 11]
06

Interacting drugs

Adenosine diphosphate (ADP) [4, 9]

5 more in the full profile.

07

Biomarkers

HDL-cholesterol levels [4, 6]Bone mineral density (BMD) [15]Intracellular cAMP levels [4, 12]IL-33 and HMGB1 levels (in asthma models) [6]

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