NASH Target Development Service for Inflammation Resolution Factor

Creative Biolabs is a global company which focuses on NASH treatment development. With our extensive experience and advanced platform, we have won a good reputation among our worldwide customers for successfully accomplishing numerous challenging projects of service targeting the inflammation resolution for the treatment of NASH. We guarantee the finest results for our customers all over the world.

Introduction of Inflammation in NASH

NASH, also known as nonalcoholic steatohepatitis, is a progressive disease state that usually found in patients of nonalcoholic fatty liver disease (NAFLD). The studies have demonstrated that the incidence of NAFLD is associated with a number of unhealthy living habits, such as high alcohol intake, overweight, over-nutrition as well as obesity. Meanwhile, pilot studies have revealed that NASH is often characterized by fatty degeneration, inflammation and hepatocellular injury. The research of NASH usually focuses on the innate immune response and anti-inflammatory effect of NASH in patients, which is important for discovering novel therapies. Furthermore, many NAFLD patients are almost related to metabolic syndrome, which is a chronic inflammatory state caused by the low activation of NF-kB. More recent researches have illustrated that a range of cytokines and transcription factors play a critical role in the development of inflammation, including IL-6, TNF-α, IL-1β and NF-kB. At present, a wide variety of targets have been identified in various animal models of NASH, such as ANXA1, pentoxifylline (PTX), RvD1, which are considered to be the key factors for developing novel therapeutic strategies for NASH treatments. As a result, their analogues, including CR-AnxA12-50, polymer-AnxA1 and lipo-RvD1, have been evaluated and widely used in a large scale of preclinical trials in NASH therapy.

Fig.1 Triggering and resolution of NASH. (Schuster, 2018)

AnxA1 Analogues

AnxA1 (also known as annexin A1 or lipocortin I) has been considered as an attractive target for NASH treatment. Recent studies have shown that AnxA1 can mediate immune response and anti-inflammatory in macrophages. The data have highlighted that AnxAL can enhance inflammation caused by the increase of macrophages and the deterioration of M1 phenotypes. Therefore, a collection of AnxA1 analogues, inhibitors, or agonists for NASH treatment have been developed in our company, including CR-AnxA12-50, Ac2-26, polymer-AnxA1 and ALX-FPR2 agonists. We also offer a panel of assays for drug development services targeting any form of AnxA1 services, including but not limited to target identification, verification and safety profiling.

Pentoxifylline (PTX) Analogues

Pentoxifylline (PTX) has shown its efficacy in patients with NASH by inhibiting the expression of tumour necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), which suggests that it is a perfect target candidate for NASH treatment. As a consequence, Creative Biolabs has developed a comprehensive platform for discovering NASH treatment by focusing on PTX or its analogues and inhibitors. We have successfully accomplished a variety of projects on evaluating the anti-TNFαagent PTX on NASH treatment. Based on our platform, TNF-α gene transcription, expression level, as well as the associated cytokine/chemokine pathways, will be analyzed. Meanwhile, we will summarize the efficacy and safety of PTX from different perspectives, which range from cytokines, liver histopathology to toxicity assessment.

RvD1 Analogues

RvD1 (resolvin D1) has been regarded as a proinflammatory facilitator in the process of the hepatic resolution by mediating the inflammatory response of patients with NASH. Currently, RvD1 or its analogues have been developed and widely used for NASH therapy. The mechanism of using RvD1 analogues for NASH treatment is based on the regulation of the transcription factors (NF-κB/AP-1 activity), the balance of cell metabolism, as well as the modification of lipoprotein toxicity and oxidative stress. Therefore, Creative Biolabs has established a panel of platforms specialized in discovering pharmacological strategies for NASH therapy. In this platform, we are focused on developing RvD1 analogues, inhibitors and agonists, such as BDA-RvD1 and lipo-RvD1 and then help our worldwide customers to assess the effectiveness and safety of drug candidates.

Fig.2 The self-resolving inflammatory process in the liver. (Musso, 2016)

Creative Biolabs is recognized as the world leader for providing the most diverse portfolio of NASH-associated target discovery solutions for worldwide customers. We are always dedicated to assisting our clients with the most satisfactory data to meet any requirement of your projects. For more information, please feel free to contact us or send us an inquiry.

References

1. Schuster, S.; et al. Triggering and resolution of inflammation in NASH. Nat Rev Gastroenterol Hepatol. 2018, 15(6): 349-364.
2. Musso, G.; et al. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nature Reviews Drug Discovery, 2016, 15(4): 249.