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As a leading preclinical CRO, Alfa Cytology has dedicated significant resources to exploring the potential of poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of various metabolic diseases. PARP has emerged as a promising therapeutic target for metabolic disease therapy.
PARP enzymes, a family of 17 proteins, were initially identified as DNA repair factors. However, recent advancements have shed light on their multifaceted involvement in various aspects of lipid metabolism, including lipotoxicity, fatty acid and steroid biosynthesis, lipoprotein homeostasis, and fatty acid oxidation. The activity of PARP enzymes is fine-tuned by a diverse set of lipid-derived molecules, such as oxidized cholesterol derivatives, steroid hormones, and bile acids.
Fig. 1 An overview of the PARP-mediated pathologies of lipid metabolism. (Szántó M., et al. 2021)
Through their interactions with lipid-responsive nuclear receptors and transcription factors, PARPs play a crucial role in regulating lipid metabolism and homeostasis. Dysregulation of PARP-mediated pathways has been implicated in the development of metabolic diseases, including hyperlipidemia, obesity, alcoholic and non-alcoholic fatty liver disease, type II diabetes, atherosclerosis, cardiovascular aging, and various skin pathologies.
Researchers have been exploring the efficacy of PARP inhibitors in animal models of various metabolic disorders. The following clinically approved PARP inhibitors are used in metabolic disease models
| Experimental Model | Disease Modelled | PARP Inhibitor | Effects |
| AML12 hepatocytes | Fatty liver Disease | Olaparib | Increased cellular bioenergetics, induction of mitochondrial biogenesis and induction of lipolysis-related genes |
| Human adipocytes subjected to differentiation | Obesity | Olaparib | Reduced fat uptake and increased mitochondrial biogenesis |
| db/db Mice | Type 2 Diabetes | Veliparib | Improved vascular function ex vivo |
Through innovative research and advanced technology, Alfa Cytology delves into the mechanisms of PARP action and has the ability to help clients develop novel PARP inhibitors, as well as optimize the effectiveness of PARP inhibitors and identify their biomarkers, to accelerate the development of new therapies for metabolic diseases.
Our services leverage cutting-edge technologies and innovative platforms to accelerate PARP inhibitor development. Alfa Cytology's preclinical research platform encompasses a diverse range of in vitro and in vivo models, as well as cutting-edge analytical technologies, to ensure a thorough evaluation of our PARP inhibitor candidates.
Therapeutics Development
Modeling Services
Preclinical Research
As a leading preclinical CRO, Alfa Cytology is committed to advancing the field of metabolic disease research and driving the development of novel PARP inhibitor. To achieve this goal, we actively engage in collaborative efforts with leading academic institutions and pharmaceutical companies. For more information about our PARP inhibitor development program for metabolic disease or to discuss potential collaborations, please don't hesitate to contact us.
Reference
For research use only. Not intended for any clinical use.
