Diabetes Drug R&D Services ace

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* Services or Products of Interest 11β-HSD1-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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11β-HSD1-Targeted Drug Development for Diabetes

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme responsible for reducing cortisone to its active form cortisol, which can lead to metabolic changes such as insulin resistance and hyperglycemia. Therefore, inhibition of 11β-HSD1 provides a novel therapeutic approach for type 2 diabetes mellitus. Ace Therapeutics is focused on helping our clients develop innovative anti-diabetic therapies targeting 11β-HSD1. Our comprehensive services encompass the entire R & D process, from target validation and high-throughput compound screening to lead compound optimization and preclinical efficacy and safety evaluation. With in-depth mechanistic studies and customized development platforms, we help our clients accelerate the development of novel 11β-HSD1 inhibitors, driving breakthroughs in diabetes therapy.

Overview of 11β-HSD1 and 11β-HSD1 Inhibitors

11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme in the regulation of glucocorticoid metabolism and is responsible for converting inactive cortisone to active cortisol. In type 2 diabetes mellitus (T2DM), cortisol exerts pathogenic effects by enhancing hepatic gluconeogenesis, decreasing insulin sensitivity, and promoting metabolic syndrome-related pathologies (e.g., hyperglycemia, obesity), making 11β-HSD1 an important target for antidiabetic drug discovery.

11β-HSD1 inhibitors for type 2 diabetes mellitus (T2DM) therapy. Fig. 1 11β-HSD1 inhibitors as type 2 antidiabetic agents. (Almeida, C.; et al., 2021)

11β-HSD1 inhibitors reduce hepatic gluconeogenesis and improve insulin resistance by blocking cortisol production and may provide additional clinical benefits such as weight loss and promotion of wound healing. Inhibitors that have reached the clinical stage (e.g., INCB13739) have shown significant reductions in fasting glucose, postprandial glucose, and glycosylated hemoglobin (HbA1c), as well as targeted inhibition of hepatic and adipose tissues, with an overall favorable safety profile. However, no phase III clinical trials have yet been conducted and there are several challenges to be addressed. Nevertheless, 11β-HSD1 remains a promising target for drug development and future studies can be expected in this field.

Ace Therapeutics' Preclinical 11β-HSD1 Inhibitor Development Services

Services	Introduction
Target validation and mechanistic studies of 11β-HSD1	Tissue-specific expression analysis: Assess 11β-HSD1 expression in target organs (e.g., liver, adipose tissue) via qPCR/Western blot to determine its link to metabolic disorders. Glucocorticoid metabolism kinetics: quantifying target inhibition by tracking cortisol/cortisone conversion using isotopic labeling.
11β-HSD1 inhibitor screening and optimization services	High-selectivity inhibitor screening: Utilizing enzyme activity assays (e.g., fluorescent substrates) and cellular models (e.g., 3T3-L1 adipocytes) to identify 11β-HSD1-selective candidates while minimizing off-target effects on 11β-HSD2 or other dehydrogenases. Structure-Activity Relationship (SAR) Optimization: Employing molecular docking and other techniques to optimize compound pharmacophores, enhancing tissue targeting and metabolic stability.
Pharmacodynamic evaluation services	Animal models of diabetes mellitus: We evaluate the effects of antidiabetic candidates on blood glucose levels, insulin sensitivity, body weight, and lipid profiles in diabetic mouse and rat models.
Safety assessment services	HPA Axis Disruption Risk Assessment: Employing dynamic monitoring of plasma ACTH and cortisol levels to evaluate the effects of long-term 11β-HSD1 inhibition on the hypothalamic-pituitary-adrenal (HPA) axis. Tissue selectivity validation: The employment of gene knockouts or tissue-specific inhibitors ensures drug targeting to liver/fat tissues and reduces systemic side effects.

Advantages of Our 11β-HSD1 Inhibitor Development Services

In vivo and in vitro models to accelerate preclinical development of antidiabetic drugs.
In-depth analysis of target inhibition mechanisms and metabolic regulatory networks.
Comprehensive and reliable toxicology and pharmacokinetic data.

Ace Therapeutics is committed to helping clients accelerate the development of antidiabetic drugs targeting 11β-HSD1 through innovative technology platforms and deep mechanistic understanding. Please feel free to contact us for further details of our services or customized development solutions.

Reference

Almeida, C.; et al. Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 as potential drugs for type 2 diabetes mellitus-a systematic review of clinical and in vivo preclinical studies. Scientia Pharmaceutica. 89.1 (2021): 5.

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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