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Inflammation is a complex and multifaceted biological response of the body's immune system to various stimuli. Chronic inflammation has been associated with a wide range of debilitating conditions, including autoimmune disorders, cardiovascular disease, and cancer. Alfa Cytology has dedicated significant resources to provides PARP inhibitor development services for combating inflammation.
PARP is a family of enzymes that play a crucial part in various cellular processes, including DNA repair, gene expression, and cell death. Importantly, PARP has been shown to be a key mediator of the inflammatory response, with its hyperactivation leading to a unique form of cell death known as parthanatos. This form of cell death is characterized by the depletion of cellular NAD+ and ATP, ultimately resulting in cell dysfunction and tissue damage.
Fig. 1 Effect of pro-inflammatory signals on PARP-1 activity. (Giansanti V., et al. 2010)
Researchers have been exploring the efficacy of PARP inhibitors in animal models of various inflammation. Through rigorous in vitro and in vivo studies, researchers have demonstrated the efficacy of these inhibitors in attenuating inflammatory responses and mitigating disease progression in various preclinical models of inflammatory disorders. The following clinically approved PARP inhibitors are used in various inflammation models.
| Experimental Model | Disease Modelled | PARP Inhibitor | Effects |
| Human CD4+ T cells stimulated with anti-CD3 and anti-CD28 | Inflammation | Olaparib | Beneficial modulation of cytokine responses and T cell subpopulations |
| HPDE cells subjected to oxidative stress | Pancreatitis | Olaparib | Protection against cell death and maintenance of cellular bioenergetics |
| Cerulein-injected mice | Acute pancreatitis | Olaparib | Improved organ function and reduced proinflammatory mediator production |
At Alfa Cytology, we offer a comprehensive suite of services to support the development of PARP inhibitors for the treatment of inflammation. Our team of experienced scientists and experts is dedicated to providing innovative solutions and tailored support to our clients throughout the drug development process.
Target Validation
We utilize cutting-edge techniques, such as high-throughput screening and computational biology, to identify novel PARP-related targets and validate their relevance in the context of inflammation. Our in-depth understanding of PARP biology and its role in the inflammatory response allows us to efficiently pinpoint key targets and investigate their therapeutic potential.
Lead Compound Optimization
Leveraging our expertise in structure-based drug design, medicinal chemistry, and advanced in silico modeling, our team works diligently to optimize the potency, selectivity, and pharmacokinetic properties of PARP inhibitor candidates. By iteratively refining the chemical structures, we strive to develop highly potent and selective PARP inhibitors with favorable drug-like characteristics.
Preclinical Evaluation
Our comprehensive preclinical evaluation capabilities include:
To support the development of innovative therapies targeting inflammatory pathways, we offer comprehensive inflammation modeling services that leverage our expertise in cellular and animal models, as well as advanced analytical techniques. At Alfa Cytology, we offer a range of inflammation models:
| Pancreas | Neuroimmunology |
In Vivo Models
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In Vivo Models
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At Alfa Cytology, we believe in fostering strong partnerships with our clients. We take a collaborative approach, working closely with our partners to understand their unique needs and challenges. By leveraging our extensive expertise in PARP biology, inflammation, and drug development, we strive to develop customized solutions that accelerate the progress of PARP inhibitor programs. To learn more about our services, please don't hesitate to contact us.
Reference
For research use only. Not intended for any clinical use.