Metabolic Diseases

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.

Introduction to PARP Inhibitor for Metabolic Diseases

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.

PARP Inhibitor Development for Metabolic Diseases

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

Our Services

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.

Fatty Liver Disease

Obesity

Diabetes

Skin Pathologies

By Services

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

Cell Line Development
3D Tumor Model
Genetically Engineered Animal Models
PDX Models

Preclinical Research

Cell-Based Assays
Mechanistic Studies
Efficacy Evaluation
ADME Evaluation
Toxicological Profiling

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

Szántó M., Gupte R., and et al. PARPs in lipid metabolism and related diseases. Prog Lipid Res. 2021, 84: 101117.

For research use only. Not intended for any clinical use.