Diabetes Drug R&D Services ace

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* Services or Products of Interest FFAR1-Targeted Drug Development for Diabetes
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* All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
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FFAR1-Targeted Drug Development for Diabetes

Free fatty acid receptor 1 (FFAR1/GPR40) has attracted widespreadattention as a promising antidiabetic target. Ace Therapeutics leveragesour expertise and advanced technology in the field of diabetes to provideglobal partners with full process development services for FFAR1-targeted drugsfrom target validation to preclinical testing.

Overview of Free Fatty Acid Receptor 1

Free fatty acid receptor 1 (FFAR1/GPR40) is highly expressed inpancreatic β-cells as a member of the G protein-coupled receptor (GPCR) family. Itsactivation significantly promotes glucose-dependent insulin secretion (GDIS),providing a novel strategy to avoid the risk of hypoglycaemia in type 2diabetes.

Pharmacodynamic Profiles of Free Fatty Acid Receptor 1 (FFAR1). Fig. 1 Pharmacological effects of FFA-1 receptors. (Dhankhar, S. et al., 2023)

Several ligands targeting FFAR1 have been functionally validated inpreclinical in vitro and in vivo studies and have shown promising antidiabetic activity.

Agonist Name	Target	Physiological Function
TAK-875	FFAR1	Stimulates glucose-dependent insulin secretion and improves glycemic control in T2DM patients
AMG837	FFAR1	Increases insulin secretion and lowers blood glucose levels in mice
GW-9508	FFAR1	Enhances insulin sensitivity andregulates glucose homeostasis
TUG-424	FFAR1	Improves glucose tolerance in mice
AM-1638	FFAR1	Increases insulin secretion andlowers blood glucose levels in mice
AM-5262	FFAR1	Enhances glucose-stimulated insulin secretion (mouse and human islets)and improves glucose homeostasis in mice
LY2881835	FFAR1	Stimulates insulin secretionfrom pancreatic β-cells
MK-2305	FFAR1	Increases glucose-stimulated insulin secretion, resulting inimprovement of glucose homeostasis in the diabetic mice

FFAR1-Targeted Antidiabetic Drug Development Services

Target validation and mechanistic studies

We use a variety of advanced technologies to help our clients validatethe therapeutic potential of FFAR1 targets.

Receptor expressionanalysis: We assess the distribution of FFAR1 in pancreas, intestine and othertissues using qPCR, Western blot (WB), and immunohistochemistry (IHC).
Signaling pathwaystudies: We analyze the downstream PLC/IP3/DAG pathway to assess synergisticeffects with GLP-1 receptors.

Screening and optimization of antidiabetic drug candidates

We use a structure-based drug design approach combined with virtual andhigh-throughput screening techniques to identify potential FFAR1 agonists orantagonists from large-scale compound libraries.

We utilize a β-lactamasereporter gene-based platform to screen for FFAR1 agonists.
We perform moleculardocking analyses to investigate the binding pocket within the FFAR1transmembrane region.

Pharmacodynamic evaluation of preclinical antidiabetic drugs

We validate the pharmacological activities of the drug candidates by in vitro experiments(e.g., cell transactivation, competitive binding assays). Meanwhile, weassessed the effects of the drug candidates on glycaemic control, insulinsecretion and metabolic functions using animal models of diabetes.

Key detection indicators：

Glucose tolerance test–GTT
Insulin tolerance test–ITT
Euglycemichyperinsulinemic clamp
Hyperglycemic clamp
Whole body glucoseturnover
In vivo individual tissueglucose uptake

Ace Therapeutics integrates advanceddiabetes animal models, computer-aided design, and interdisciplinary research,and is dedicated to the development of safe and effective FFAR1-targetedantidiabetic drugs. We provide innovative solutions to our clients through fullprocess support from target identification to preclinical evaluation. Please contact us for more details.

References

Dhankhar, S.; et al. Novel targets for potential therapeutic use inDiabetes mellitus. Diabetology& Metabolic Syndrome. 2023, 15(1): 17.
Al, Mahri. S.; et al. Free fatty acid receptors (FFARs) inadipose: physiological role and therapeutic outlook. Cells. 2022, 11(4): 750.
Chen, Y.; et al. HWL‐088, a new potent freefatty acid receptor 1 (FFAR1) agonist, improves glucolipid metabolism and actsadditively with metformin in ob/ob diabetic mice. British Journal of Pharmacology. 2020,177(10): 2286-2302.
Rani, L.; et al. Recent updates on free fatty acid receptor 1 (GPR-40)agonists for the treatment of type 2 diabetes mellitus. Mini Reviews in MedicinalChemistry. 2021, 21(4): 426-470.
Li, Z.; et al. Free fatty acid receptor 1 (FFAR1) as an emergingtherapeutic target for type 2 diabetes mellitus: recent progress and prevailingchallenges. Medicinalresearch reviews. 2018, 38(2): 381-425.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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