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Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), a heterotrimeric serine/threonine kinase, acts as a central regulator of cellular energy homeostasis by phosphorylating downstream targets in glucose and lipid metabolism pathways. Ace Therapeutics provides antidiabetic drug development services targeting AMPK. Leveraging our extensive diabetes models and preclinical testing platform, we help clients accelerate the drug development process from target validation to preclinical evaluation.
AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low and signals to stimulate glucose uptake in skeletal muscle, fatty acid oxidation in adipose (and other) tissues, and to reduce hepatic glycogen production. Multiple effects of AMPK activation in liver and muscle improve metabolic control. These effects include:
Fig. 1 Modulators of AMPK activation. (Zhang, B. B.; et al., 2009)
AMPK's extensive regulatory roles in lipid and glucose metabolism render it a highly attractive therapeutic target. Numerous pharmaceuticals, natural compounds, and hormones can directly or indirectly activate AMPK, with several (e.g., metformin and thiazolidinediones) currently employed in type 2 diabetes treatment. The development of potent and selective AMPK activators holds significant promise for managing type 2 diabetes and related metabolic disorders.
We elucidate the assembly of AMPK α/β/γ subunits and their allosteric regulatory mechanisms, precisely mapping the binding sites of candidate compounds to facilitate drug design and optimization.
We validate the specific effects of drugs on the AMPK pathway by testing Thr172 phosphorylation level, ACC activity and other key indicators to ensure targeting and efficacy.
We employ both in vitro and in vivo models to evaluate the hypoglycemic and hypolipidemic effects of AMPK agonists. For in vitro studies, we use high glucose-treated hepatocytes and myotubes, while for in vivo validation, we utilize db/db mice.
We provide comprehensive AMPK agonist discovery and optimization services, covering the entire process from high-throughput screening to lead compound optimization, to help accelerate the drug discovery process.
We construct activity detection systems for AMPK α/β/γ subunit combinations based on structural biology analysis to screen potential agonists.
We use biochemical and cellular level high throughput screening (HTS) to rapidly identify candidate molecules with AMPK activation activity.
We optimize the molecular structure based on ADMET (absorption, distribution, metabolism, excretion, toxicity) properties to improve drugability.
We screen low-toxicity and high-stability drug candidates through in vitro liver microsomal stability, CYP450 inhibition assay and cytotoxicity testing.
We utilize humanized AMPKα2 knock-in mice on HFD/STZ-induced insulin resistance models and high-fat diet (HFD) models to help clients validate the glucose-lowering, lipid-reducing, and insulin-sensitizing effects of AMPK activators.
We provide comprehensive PK/PD (pharmacokinetics/pharmacodynamics) analysis to optimize dosing regimens.
We provide comprehensive preclinical pharmacodynamics (PD) and safety evaluation services during the development of AMPK-targeted antidiabetic drugs. Our services cover in vitro, ex vivo and in vivo evaluations at multiple levels, helping our clients accelerate the drug development process.
If you are developing AMPK-targeted antidiabetic therapeutics, Ace Therapeutics invites you to collaborate with us. Please contact us and we will provide end-to-end solutions, from target discovery to preclinical studies, tailored to your specific needs.
Ace Therapeutics has a team of experts in the field of endocrine and metabolic research, aiming to provide innovative preclinical contract research solutions to cope with diabetes and its complications. We provide customized solutions and technical support, enabling the transformation of promising concepts into innovative treatments, thus accelerating the drug development process of diabetes.
