AI Article Synopsis
- The study focuses on FFA1/GPR40 as a new target for diabetes treatment and introduces a series of new compounds designed to enhance its activation.
- The most effective compound, compound 17, showed much higher activity (45.78%) compared to the previously tested compound (15.32%).
- In experiments with mice, compound 17 significantly lowered blood glucose levels and improved glucose tolerance, indicating its potential as a strong candidate for future antidiabetic drug development.
Article Abstract
The free fatty acid receptor 1 (FFA1/GPR40) has attracted extensive attention as a novel antidiabetic target. Aiming to explore the chemical space of FFA1 agonists, a new series of lead compounds with amide linker were designed and synthesized by combining the scaffolds of NIH screened lead compound 1 and GW9508. Among them, the optimal lead compound 17 exhibited a considerable agonistic activity (45.78%) compared to the NIH screened compound 1 (15.32%). During OGTT in normal mice, the compound 17 revealed a significant glucose-lowering effect (-23.7%) at the dose of 50mg/kg, proximity to the hypoglycemic effect (-27.8%) of Metformin (200mg/kg). In addition, the compound 17 (100mg/kg) also exhibited a significant improvement in glucose tolerance with a 29.1% reduction of glucose AUC in type 2 diabetic mice. All of these results indicated that compound 17 was considered to be a promising lead structure suitable for further optimization.
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| http://dx.doi.org/10.1016/j.bmc.2017.03.001 | DOI Listing |
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