AMG 837 (calcium hydrate)

AMG 837 calcium hydrate is an orally active, selective GPR40/FFA1 agonist with an EC₅₀ of 1.5 nM against human GPR40. AMG 837 calcium hydrate stimulates insulin secretion in a glucose-dependent manner, and effectively improves glycemic control in both normal and diabetic rodent models. AMG 837 calcium hydrate binds to the BacA protein and impairs the survival and replication of Brucella. AMG 837 calcium hydrate can be used in research related to type 2 diabetes and brucellosis^[1][2]. IC50 & Target:pIC50: 8.13 (FFA1)^[3] In Vitro:AMG 837 calcium hydrate stimulates inositol phosphate accumulation in A9_GPR40 cells with an EC₅₀ of 7.8 nM^[1].
AMG 837 calcium hydrate potently and selectively stimulates Ca²⁺ influx mediated by human GPR40 in CHO cells, with an EC₅₀ of 13.5 nM, and shows no activity against the homologous human GPR41, GPR43 or GPR120 receptors^[1].
AMG 837 calcium hydrate activates GPR40 across multiple preclinical species, with EC₅₀ values of 22.6 nM in mice, 31.7 nM in rats, 71.3 nM in dogs, and 30.6 nM in rhesus monkeys in the CHO cell aequorin assay^[1].
The potency of AMG 837 calcium hydrate against human GPR40 decreases in the presence of serum albumin or human serum, with an EC₅₀ value of 210 nM in 0.625% HSA and 2140 nM in 100% human serum^[1].
AMG 837 (1 μM) calcium hydrate enhances insulin secretion activity of primary mouse islets in a glucose-dependent manner^[1].
AMG 837 calcium hydrate inhibits the growth of B. melitensis TZ, B. melitensis M5-90, B. suis S2, and B. abortus A19^[2].
AMG 837 (4-16 μg/mL; 6-48 h) calcium hydrate effectively inhibits B. melitensis TZ in RAW264.7 cells at a concentration of 4 μg/mL, and completely eliminates the bacterium at 16 μg/mL following 6, 12, 24, and 48 h of incubation^[2]. In Vivo:AMG 837 (0.03-0.3 mg/kg; p.o.; single administration) calcium hydrate improves glucose tolerance in a dose-dependent manner in normal Sprague-Dawley rats^[1].
AMG 837 (0.3 mg/kg; p.o.; single administration) calcium hydrate effectively improves glucose tolerance and increases glucose-stimulated insulin secretion in normal Sprague-Dawley rats even after two consecutive glucose challenges^[1].
AMG 837 (0.3-3 mg/kg; p.o.; single administration) calcium hydrate reduces the postprandial blood glucose AUC_0-t by approximately 46% in insulin-resistant Zucker obese rats by enhancing glucose-stimulated insulin secretion^[1].
AMG 837 (0.03-0.3 mg/kg; p.o.; once daily for 21 days) calcium hydrate maintains the efficacy of improving glucose tolerance in insulin-resistant Zucker obese rats, and reduces glucose AUC_0-t by 25% at the dose of 0.3 mg/kg on day 21 of administration; its mechanism of action is to continuously stimulate insulin secretion via glucose, without affecting the body weight of rats^[1].