LY2922470 / Eli Lilly - LARVOL DELTA

AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner. (PubMed, Endocrinol Metab (Seoul)) - "Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • CASP3 • HMOX1 • XBP1

GPR40 agonist, an emerging antidiabetic agent, regulates foam cell formation and endothelial cytotoxicity (EASD 2023) - "Both LY2922470 and TAK875 significantly reduced palmitate mediated endoplasmic reticulum (ER) stress, caspase-3 and poly ADP-ribose polymerase (PARP) cleavage and lactate dehydrogenase (LDH) release. GPR40 has beneficial effects on metabolic stimuli in vascular endothelial cells and THP-1 cells. Since chronic and excessive inflammation and cytotoxicity are known to be responsible for foam cell formation, plaque development and plaque instability, GPR40 might represent a good therapeutic target to overcome cardiovascular diseases (CVD) such as atherosclerosis."

Diabetes • Metabolic Disorders • AMPK • CASP3 • CD36

G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice. (PubMed, Int J Mol Sci) - "Here, we first reveal that the transcriptomic gene signature induced by LY2922470 is highly similar to those induced by some agents being involved in defending from cerebrovascular accidents and transient ischemic attacks, including acetylsalicylic acid, progesterone, estradiol, dipyridamole, and dihydroergotamine. As a result, further experiments show that giving the small molecule LY2922470 via oral administration or intraperitoneal injection was seen to have a positive effect on neuroprotection with a reduction in infarct size and an improvement in motor skills in mice. Finally, it was demonstrated that LY2922470 could successfully mitigate the harm to the brain caused by ischemic stroke."

Journal • Preclinical • Cardiovascular • CNS Disorders • Diabetes • Ischemic stroke • Metabolic Disorders • Type 2 Diabetes Mellitus • Vascular Neurology

GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells. (PubMed, Diabetes Metab J) - "LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium."

Journal • Cardiovascular • Immunology • Inflammation • ICAM1 • VCAM1

A study of LY2922470 in healthy participants and participants with diabetes (clinicaltrials.gov) - P1, N=25; Sponsor: Eli Lilly and Company; Recruiting -> Completed.

Trial completion • Diabetes