AZD-1656(CAS:919783-22-5)

AZD-1656 (CAS 919783-22-5) is a highly selective glucokinase activator originally developed by AstraZeneca. With an ultra-low EC50 of 60 nM, excellent oral bioavailability and unique dual regulatory mechanism covering metabolism and immunity, it has become a benchmark core research API for global scientific institutions and pharmaceutical CROs focusing on glucose metabolism disorders and autoimmune diseases. It has a molecular formula of C₂₄H₂₆N₆O₅ and a molecular weight of 478.5, appearing as off-white solid powder with stable physicochemical properties. Resistant to degradation under normal temperature and light shielding, it has a longer shelf life under low-temperature freezing storage. With strictly controlled related substances, residual solvents and heavy metals, it features reliable batch stability and experimental repeatability, fully supporting in vitro target verification, cell function assays, diabetic animal modeling, autoimmune disease efficacy evaluation and high-throughput compound screening.

In terms of core pharmacological mechanism, glucokinase (GK) acts as the core "blood glucose sensor" and rate-limiting enzyme for hepatic glucose metabolism and pancreatic insulin secretion. Impaired GK function is a common pathological feature of type 2 diabetes, leading to dysfunctional glucose sensing, abnormal hepatic glucose output and delayed insulin secretion. As a potent GK activator, AZD-1656 precisely binds and enhances glucokinase activity to reshape the human blood glucose homeostasis system. In pancreatic tissue, it repairs the glucose sensing function of β-cells and promotes accurate insulin secretion only under hyperglycemia, completely avoiding fasting hypoglycemia risks. In the liver, it effectively inhibits hepatic gluconeogenesis and glycogenolysis, reduces endogenous glucose release, lowers fasting blood glucose and ameliorates peripheral insulin resistance, stabilizing all-day glycemic fluctuation. Different from traditional sulfonylureas and DPP4 inhibitors, it repairs metabolic pathways fundamentally with superior physiological compatibility, safety and long-term regulatory performance.

Beyond classic hypoglycemic activity, the differentiated core advantage of AZD-1656 lies in its unique immunomodulatory and anti-inflammatory effects, breaking the application limitation of traditional GK activators that only target metabolic diseases. Preclinical and Phase 2a clinical studies have verified that AZD-1656 efficiently regulates abnormal immune inflammatory responses and inhibits the activation of autoimmune antibodies and pro-inflammatory factors. Currently, its clinical pipelines cover systemic lupus erythematosus, lupus nephritis, ANCA-associated vasculitis, uveitis and autoimmune thyroid diseases. As a rare dual-target tool compound acting on both metabolic and immune pathways, it has also been applied in metabolic immune intervention research for COVID-19 patients complicated with diabetes, delivering outstanding cross-disciplinary research value.

In terms of scientific research and industrial value, AZD-1656 adopts mature synthesis and purification technology with strict impurity control, stably supplying high-purity raw materials from milligram to kilogram scale to meet diverse demands of basic scientific research and preclinical new drug development. It exhibits excellent long-term administration tolerance without obvious liver or kidney cumulative toxicity and a wide safety experimental window, suitable for long-term in vivo efficacy verification and in-depth mechanism exploration. With the booming global R&D of new drugs for metabolic and autoimmune diseases, the GK target has become a research hotspot spanning hypoglycemic treatment and immune anti-inflammation. Endowed with definite dual pharmacological mechanisms, complete in vitro and in vivo activity data and abundant clinical research support, AZD-1656 serves as an essential rigid-demand raw material for GK target structural optimization, positive control experiments and combined regimen exploration, maintaining irreplaceable long-term research value in metabolic pharmacology, immune inflammation mechanism research and innovative dual-target drug development worldwide.