Delving into the Latest Updates on LY-2922470 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

GPR40

Mechanism

GPR40 agonists(Free fatty acid receptor 1 agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.

Eli Lilly & Co.

Drug Highest PhasePendingPhase 1/2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC28H29NO4S

InChIKeyVJVDLRVFJTVWEO-QFIPXVFZSA-N

CAS Registry1423018-12-5

The main purpose of this study is to determine the safety of LY2922470, taken as oral capsules, once or twice daily for approximately 28 days, in participants with diabetes. It also aims to determine how long the drug stays in the body and how it affects blood sugar levels. A screening appointment is required within 28 days before the start of the study and a follow up appointment is required approximately 14 days after the last study dose is taken.

Start Date01 Jun 2013

Sponsor / Collaborator

Eli Lilly & Co.

NCT01746017 / CompletedPhase 1

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Oral Doses of LY2922470 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus

The aim of this trial is to evaluate the safety of the study drug in healthy participant and participant with diabetes. It will investigate how much of the study drug gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected.
The study consists of two parts. Part A will study healthy participants in up to 4 dosing periods over approximately 6 weeks. Part B will study participants with diabetes in up to 3 dosing periods over approximately 5 weeks.

Start Date01 Dec 2012

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with LY-2922470

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100 Translational Medicine associated with LY-2922470

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100 Patents (Medical) associated with LY-2922470

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5

Literatures (Medical) associated with LY-2922470

31 Dec 2023·Endocrinology and Metabolism

AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner

Article

Author: Park, Min Jeong ; Baik, Sei Hyun ; Jang, Ahreum ; Kim, Joo Won ; Yun, SukHwan ; Choi, Kyung Mook ; Song, Eyun ; Hwang, Hwan-Jin ; Jang, Sooyeon ; Yoo, Hye Jin

Background: G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress.Methods: Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium.Results: In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. 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. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner.Conclusion: GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

31 Jul 2023·International journal of molecular sciences

G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice.

Article

Author: Lu, Yingyu ; Cui, Chunmei ; Zhou, Wanlu ; Cui, Qinghua

Stroke is a major cause of fatalities and disabilities around the world, yet the available treatments for it are still limited. The quest for more efficacious drugs and therapies is still an arduous task. LY2922470 is currently used as a G protein-coupled receptor 40 (GPR40) agonist for the treatment of type 2 diabetes. Previous studies have reported protective effects of other GPR40 activators on the brain; however, it remains unclear whether LY2922470 could be a new stroke therapy and improve the stroke-induced brain damage. 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. This result thus suggests that LY2922470 could have protective effects against ischemic stroke. 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.

31 May 2022·Diabetes & Metabolism JournalQ3 · MEDICINE

GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells

Q3 · MEDICINE

ArticleOA

Author: Baik, Sei Hyun ; Yoo, Hye Jin ; Choi, Kyung Mook ; Roh, Eun ; Hwang, Hwan-Jin ; Kim, Joo Won

Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. 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.

100 Deals associated with LY-2922470

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	CN	Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.	22 Jun 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01867216 (CTgov)	Phase 1	Diabetes Mellitus, Type 2	66	Placebo (Placebo QD or BID)	tbbqzxfuyl(ssryqgrszi) = zmfhpnllut zqsjpdihbe (iqfblqpfrf, aufgqgzgnb - wfkrryvrqp) View more	-	26 Jul 2018
				LY2922470 (60 mg LY2922470 QD)	tbbqzxfuyl(ssryqgrszi) = iikdjsymdf zqsjpdihbe (iqfblqpfrf, kweslucqpz - tuxyecishb) View more