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Targeting Enzymes and Proteins for Developing Anti-Obesity Therapeutics

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Cruciality of Developing Anti-obesity Therapies

Obesity is a multifaceted disease influenced by genetic, environmental, and behavioral factors. It is spreading globally and causes related complications such as cardiovascular disease, type 2 diabetes, cancer, metabolic syndrome, etc. These complications not only reduce an individual's quality of life but also place a significant burden on the healthcare system. Additionally, obesity-related diseases lead to increased mortality and may significantly shorten life expectancy. Obesity is difficult to control through lifestyle changes alone. Effective anti-obesity therapies target underlying biological mechanisms to help regulate appetite, increase metabolism and improve energy expenditure. Given the multifactorial nature of obesity, Protheragen has established a dedicated obesity research team to develop targeted therapies for Hormones and Peptides, Receptors, Enzymes and Proteins, Metabolic Regulators, and Signaling Molecules, providing hope for long-term weight management and improving metabolic health.

Fig.1 Obesity causes complications such as cardiovascular disease and insulin resistance.Fig.1 Complications caused by obesity. (Cai, et al., 2023)

Precision Power: Targeting Enzymes and Proteins for Anti-obesity Breakthroughs!

The roles of enzymes and proteins in metabolic processes, appetite regulation, and energy homeostasis make them ideal targets for treating obesity. By understanding and manipulating these biomolecules, researchers are developing a variety of anti-obesity therapies that inhibit or activate specific proteins and enzymes associated with fat storage, metabolism, and appetite control. Compared to traditional therapies, targeted therapies offer more precise and effective solutions, potentially reducing side effects and improving treatment outcomes. With years of research experience in the field of obesity, we target the following proteins and enzymes to develop safe and effective anti-obesity therapies.

We also target other enzymes and proteins to develop anti-obesity therapies, including but not limited to:

Targets Description
AMP-activated protein kinase (AMPK) A key regulator of energy balance at the cellular level. Activating AMPK enhances energy expenditure and reduces fat accumulation.
Lipoprotein lipase (LPL) An enzyme involved in the breakdown of lipids. Modulating LPL activity affects fat storage and metabolism.
Fat mass and obesity-associated protein (FTO) Genetic variations in FTO are linked to increased obesity risk. Targeting FTO might help in managing obesity.

Our development process for anti-obesity therapeutics targeting enzymes and proteins is as follows:

  • Target Validation

    We use methods such as genomic, proteomic, and bioinformatic analysis to identify potential targets and confirm their relevance and functionality through experimental validation. For example, knockdown or knockout experiments are performed in In Vitro Cell Models and In Vivo Animal Models to observe the phenotypic consequences of inhibiting or enhancing target activity. Biochemical assays and pathway analyses are used to determine the mechanistic rationale for targeting specific enzymes or proteins. In summary, ensuring the validation of the right target helps streamline the subsequent stages of therapeutic development and improve the efficacy and safety of anti-obesity therapies.

  • Preclinical Studies

    We start with in vitro experiments to assess the activity and target specificity of the therapy, whether it is a small molecule, antibody, or gene therapy, followed by in vivo testing in obese animal models such as diet-induced obese mice or transgenic rodents to assess the Pharmacokinetics, Pharmacodynamics, Safety, and more.

Workflow

Strategies for anti-obesity therapy development targeting enzymes and proteins. (Protheragen)

Applications

  • Targeting MetAP2, UCP, RXR, etc., to develop new obesity treatment drugs, which regulate metabolic pathways related to energy balance, reduce fat accumulation, enhance lipid metabolism, and ultimately help lose weight and improve metabolic health.
  • Genes encoding enzymes and proteins related to obesity are encoded through precise gene editing tools to develop gene therapies for obesity treatment.
  • Explore biomarkers associated with these enzymes and proteins to create diagnostic tools for early detection of obesity-related metabolic disorders, and achieve personalized treatment plans and preventive measures.

Advantages

  • We use advanced technologies such as HTS and next-generation sequencing (NGS) to identify and validate key enzymes and proteins associated with obesity and develop potential therapeutics based on them.
  • Our integrated multi-omics platform covers genomics, proteomics, and metabolomics, providing a holistic view of the molecular mechanisms of obesity and facilitating the development of highly specific and effective inhibitors or modulators.
  • We provide comprehensive bioassays to validate the functionality of therapeutic candidates, such as measuring the bioactivity, binding efficiency, and metabolic impact of enzyme and protein inhibitors.
Our Services

We provide comprehensive analytical services to advance obesity-related research to meet the unique needs of our clients. Our team of experts uses cutting-edge methods and analytical tools to conduct in-depth studies and trials to explore the multifaceted issues of obesity, such as obesity causation analysis and obesity prediction services. We customize research protocols, data collection, and analytical services to ensure scientifically sound and actionable insights. Clients benefit from our collaborative approach that combines the latest scientific advances with personalized guidance to provide new insights into the development of therapies to address obesity. Our services include:

Publication Data

DOI: 10.1074/jbc.RA118.007302

Journal: Journal of Biological Chemistry

Published: 2019

IF: 4.0

Results: The authors used MetAP2 inhibitors with different chemical scaffolds to explore the anti-obesity mechanism of MetAP2 inhibition, and the results showed that MetAP2 inhibitors reduced body weight and obesity in obese mice, but not in lean mice. The authors treated brown adipose tissue and brown adipocytes with MetAP2 inhibitors, and norepinephrine-induced lipolysis and energy expenditure were enhanced, and UCP1 gene expression and energy expenditure in norepinephrine-desensitized brown adipocytes were enhanced. In conclusion, MetAP2 inhibitors may mediate brown adipocytes by enhancing β-adrenergic signaling stimulatory activity.

Fig.2 MetAP2 inhibitors increase lipolysis and energy expenditure in brown adipocytes.Fig.2 MetAP2 inhibitors increase norepinephrine-induced lipolysis and energy expenditure in primary brown adipocytes. (Huang, et al., 2019)

Frequently Asked Questions

Why focus on enzymes and proteins to develop anti-obesity therapeutics?

Enzymes and proteins are important regulators of metabolic pathways and physiological processes that regulate energy balance, fat storage, and appetite control. Targeting specific enzymes and proteins controls key biochemical cascades involved in lipid metabolism, lipogenesis, and thermogenesis, providing precise intervention points to reduce excess fat accumulation. For example, MetAP2 has been shown to affect lipid metabolism and nutrient absorption and are promising targets for the development of anti-obesity drugs.

What preclinical approaches are used to ensure the safety and efficacy of therapies targeting enzymes and proteins?

First, extensive in vitro studies are performed to analyze the biological functions of potential molecules on target enzymes and proteins. Then, preclinical trials are conducted using animal models to evaluate the therapeutic potential and pharmacokinetic properties of candidate therapies. These studies are designed to determine the optimal dose, absorption, distribution, metabolism, and excretion profile of the therapy while evaluating its safety through toxicology assessments.

Protheragen uses cutting-edge science and unparalleled expertise to help you explore the future of obesity treatment. For more information on targeted enzyme and protein-related obesity therapy research, please feel free to contact us. Our team is ready to provide detailed insights and solutions on the latest advances in this field.

References

  1. Cai, Y.; et al. Biomarkers of obesity-mediated insulin resistance: focus on microRNAs. Diabetology & Metabolic Syndrome. 2023, 15: 167.
  2. Huang, H.J.; et al. MetAP2 inhibition increases energy expenditure through direct action on brown adipocytes. Journal of Biological Chemistry. 2019, 294(24): 9567-9575.

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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