Targeting Neurokinin Receptor for Developing Anti-Obesity Therapeutics
InquiryOverview
The global obesity epidemic continues to surge, posing a major public health challenge affecting hundreds of millions worldwide. While GLP-1 agonists and other incretin therapies have revolutionized weight management, significant limitations persist in clinical practice. There is an urgent need to explore targets with superior therapeutic indices and develop novel therapeutic agents to achieve weight reduction and effectively address the cascade of associated complications. Neurokinin receptors (NKRs), a class of Gq-coupled receptors, are emerging as frontier targets in drug development for metabolic disorders (diabetes, obesity). Among these, NK2R has garnered particular attention. Research has demonstrated that NK2R activation modulates appetite and energy expenditure, improves insulin sensitivity, and significantly reduces body weight, blood glucose, triglycerides, and cholesterol levels in obese animals. Therapies targeting NKRs offer a novel therapeutic pathway for obesity treatment with potential high tolerability, low side effects, and complementary mechanisms of action.
Your Most Trusted Research Partner in Anti-obesity Therapies
Protheragen possesses extensive research experience in Anti-obesity Studies and leverages specialized technical platforms to support the development of high-quality anti-obesity therapies targeting NKRs, particularly NK2R. Our strategy is built upon a deep scientific understanding of relevant pharmacology and energy homeostasis regulation, offering end-to-end services from therapeutic design to preclinical research.
Anti-Obesity Drug Development
We employ advanced computational structural biology and molecular docking studies to design molecules with high affinity and functional bias, or identify potential leads with good specificity through high-throughput screening of compound libraries. We then analyze these drug candidates' properties (functional bias, bioavailability, druggability, ADMET analysis, etc.) and optimize them to meet requirements for targeting and efficacy. Through iterative cycles of chemical synthesis, structural analysis, and multi-assay testing, we refine lead compounds and select highly specific, well-characterized anti-obesity drug candidates for subsequent preclinical studies.
Preclinical Studies
We evaluate the anti-obesity potential of potential NK2R modulators using diverse obesity models, including:
We systematically monitor candidate drug efficacy in relevant animal models, with core metrics including body weight, body fat percentage, suppression of food intake, etc.
We systematically evaluate drug absorption, distribution, metabolism, and excretion processes, conducting detailed analyses of metabolic stability, drug interactions, bioavailability, etc.
Bioanalysis serves as the analytical foundation throughout all preclinical stages, ensuring quantitative accuracy of drugs, metabolites, and biomarkers in biological samples. We employ highly sensitive and specific analytical methods (e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS)) to determine concentrations of candidate drugs and metabolites in plasma, tissues, and urine. This supports pharmacokinetic parameter calculations and provides data for analyzing drug utilization and efficacy.
We conduct comprehensive safety and toxicity evaluations of drug candidates to maximize therapeutic benefits while mitigating risks. These studies encompass acute toxicity testing, subchronic toxicity studies, target organ toxicity assessments aligned with drug characteristics (particularly for the liver, kidneys, and cardiovascular system), etc.
Workflow
We focus on developing highly promising anti-obesity therapeutic strategies with well-defined mechanisms. Leveraging cutting-edge technologies—such as cryo-EM structural analysis and functionally biased screening—alongside deep scientific expertise, we rationally design and synthesize specific agonists (small molecules or peptides) that target and activate NK2R, or other highly effective therapeutic approaches. A mature, multi-stage workflow ensures efficient advancement of anti-obesity therapeutic candidates from concept to validation lead compounds. Each step is meticulously designed to provide clients with a clear and efficient R&D pathway.
Applications
Targeting NK2R represents a core strategic direction for developing next-generation anti-obesity drugs, offering a novel and more competitive therapeutic option.
The discovery and research of NK2R agonists provide novel molecular tools for delving into the complex mechanisms of obesity.
Potential anti-obesity therapies targeting NK2R may also hold therapeutic promise for treating a range of core cardiovascular and metabolic dysfunctions associated with obesity.
Advantages
Focus on Complex GPCRs and Function-Directed Approach
Leveraging years of expertise in complex metabolic targets, we utilize advanced function-directed screening technologies and high-resolution structural biology platforms to precisely guide the development of highly selective agonists.
Efficient Therapeutic Development
Leveraging our deep expertise in the field of NK2R agonists, we excel at efficient drug structure design and optimization to ensure that the developed compounds not only exhibit potent activity but also possess excellent bioavailability and favorable pharmacokinetic properties.
Comprehensive Early-Stage Evaluation
We systematically integrate ADMET predictions, pharmacokinetics, and critical specificity/safety assessments during early lead optimization. This holistic approach efficiently eliminates poorly druggable or potentially unsafe molecules, significantly reducing late-stage preclinical risks and costs.
Protheragen provides core NK2R-targeted therapy development services while also focusing on building integrated, high-translation multidimensional analytical solutions. We aim to comprehensively empower our clients' obesity research through precise testing and analysis, utilizing cutting-edge omics technologies to thoroughly investigate the complex biological mechanisms of obesity and provide reliable support for diverse research endeavors.
Publication Data
Title: Beyond incretins: targeting neurokinin receptors for obesity treatment
Journal: Signal Transduction and Targeted Therapy, 2025
DOI: https://doi.org/10.1038/s41392-024-02100-y
Summary: Researchers have developed a potential novel anti-obesity therapeutic strategy: an obesity treatment targeting NK2R. NK2R has been identified as a novel regulator of food intake and energy expenditure. NK2R selective agonists effectively activate NK2R to reduce food intake, body weight, and white adipose tissue mass while improving insulin sensitivity and demonstrating significant weight loss effects. Furthermore, combining the positive effects of NK2R with incretin receptor agonists may further enhance the therapeutic potential for obesity treatment.
Customer Review
Unparalleled Scientific Depth
"Protheragen's scientific depth in drug prediction is unmatched. They conduct detailed assessments of our compounds' ADMET properties and provide reliable data. This enables us to identify potential drugability risks early and reduce trial-and-error costs in subsequent R&D."— L. M., Research Fellow
Stringent Screening
"Protheragen's high-standard specificity and functional bias screening proved crucial, enabling us to rapidly select a specific and safe lead candidate for seamless progression into subsequent studies. They are an exceptionally reliable service provider."— M. T., Medicinal Chemist
Frequently Asked Questions
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How does Protheragen ensure subtype selectivity?
We employ an advanced approach combining multi-functional assays based on the mature NK2R structure with computational modeling. This system enables simultaneous determination of functional activity and binding affinity for all three vasopressin receptor subtypes during early discovery stages. This rigorous screening process eliminates cross-reactive compounds, ensuring exceptional selectivity.
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How do we initiate discussions with Protheragen regarding the NK2R project collaboration?
We recommend contacting our scientific business development team to schedule a confidential consultation. We will tailor proof-of-concept studies leveraging our core technologies or establish a comprehensive exploratory collaboration framework to perfectly align with your strategic objectives in the anti-obesity drug field.
Protheragen is your ideal partner for developing next-generation anti-obesity therapies. Leveraging deep insights into NK2R-specific screening and advanced technologies, we ensure your innovative candidates overcome challenges to deliver dual therapeutic benefits: appetite suppression and enhanced energy expenditure. Welcome to contact us to explore your targeted research projects in depth.
Reference
- Thor, D.; Prömel, S. Beyond incretins: targeting neurokinin receptors for obesity treatment. Signal Transduction and Targeted Therapy. 2025, 10(1): 21. (CC BY 4.0)
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
