NASH Target Development Service for CYR61 Analogues

Nonalcoholic steatohepatitis (NASH) remains a major cause of liver-related morbidity and mortality worldwide. The CYR61 has been proved to be involved in the NASH process. Hence, the CYR61 obtains much attention due to its therapeutic potential ability for the treatment of NASH as a target. As one of the most competitive biotechnology companies in the world, Creative Biolabs has extensive expertise and experience to provide you target identification for drug discovery and drug development services. In terms of sophisticated equipment, advanced technologies, and highly experienced staff, we can provide you with the most affordable and high-quality CYR61 analogues for the treatment of NASH to ensure your satisfaction in a timely and professional manner.

Introduction of CYR61

Cysteine-rich angiogenic inducer 61 (CYR61) (also named CCN1) was first identified as a cysteine-rich (CYR) protein encoded by a serum-inducible immediate-early gene product in mouse fibroblasts. CCN1 and other highly conserved homologs consist of the CCN protein family, which has six members in mammals. CYR61 is a dynamically expressed, multifunctional matricellular protein that presents versatile functions. It can promote cell survival and trigger apoptosis, enhance cell proliferation but also induce cell-cycle arrest, and promote tumor growth and suppress tumorigenesis in a variety of contexts. These diverse activities of CCN1 can in large parts depend on its interaction with distinct integrins and heparan sulfate proteoglycans (HSPGs) in a cell-type and context-dependent manner. Current data have confirmed that CCN1 is essential for cardiovascular development during embryogenesis, and important for modulating inflammation, wound healing, and tissue repair in many tissues of the adult. Aberrant CCN1 expression is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation, indicating that targeting CCN1 expression and signaling may harbor promise in the development of diagnostic markers and therapeutics.

Fig.1 Structure of CCN family members. (Leask, 2006)

CYR61 Analogues for NASH Treatment

Recent studies show that CYR61 plays a role in limiting fibrosis in liver models. It expresses in primary profibrogenic liver cells and was found an increase expression during early activation of hepatic stellate cells while expression declined during prolonged phases of fibrogenesis. CYR61 has been shown to activate the NF-κB signaling pathway in macrophages, resulting in the expression of various pro-inflammatory cytokines and chemokines, characterized by classically activated M1 macrophages. Moreover, CYR61 further induces production of reactive oxygen species (ROS) and can also attenuate TGF-β signaling resulting in cellular senescence and apoptosis as well as mitigating liver fibrogenesis. Furthermore, it was shown that endotoxins and free fatty acids (FFAs) induce expression of the matricellular signaling molecule CYR61 in hepatocytes of mice models. CYR61 can drive macrophage recruitment into the steatotic liver, inducing the inflammatory process and macrophage infiltration. The potential role of CYR61 in the transition from simple steatosis to NASH in humans will be worth exploring in future studies. Thus, CYR61 or its analogues may become potential therapeutic targets for NASH prevention.

Fig.2 Schematic of CCN1 functions in ER-stress-induced hepatic stellate cells (HSC) apoptosis. (Borkham-Kamphorst, 2016)

Features

• Various available methods for selective analysis of novel drugs
• Years of experience in target development and drug discovery
• Rapid turnaround time
• Strict quality control and competitive price

Creative Biolabs is an innovative and reliable partner for your research. We are dedicated to ensuring that our services on CYR61 analogues are at the highest level of quality. Our experienced scientists are committed to identifying the compounds with the greatest chance to succeed. Meantime, based on the commitment of prompt communication and on-time reporting, our staff will ensure a high-efficiency service to meet the strict project timelines. Please feel free to contact us.

References

1. Leask, A.; Abraham, D.J. All in the CCN family: essential matricellular signaling modulators emerge from the bunker. Journal of cell science. 2006, 119(23): 4803-4810.
2. Borkham-Kamphorst, E.; et al. CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis. Cellular signaling. 2016, 28(1): 34-42.