Current Drug Targets - Volume 24, Issue 15, 2023

Syndecan-1 (SDC-1), known as a coreceptor of various growth factors or an integrin binding partner, regulates various cell behaviours. Under certain pathological conditions, SDC-1 is shed from the cell surface and plays a protective or pathogenic role in various diseases. In the liver, SDC-1 is highly expressed in hepatocytes, where it is localized on the basolateral surface. It is critical to the cellular and molecular functions of hepatocytes, including their attachment to hepatitis viruses. Previous studies have reported that SDC-1 may function as a novel and promising diagnostic and therapeutic marker for various liver diseases, such as drug-induced liver injury, liver fibrosis, and liver cancer. In this review, we summarize related research and highlight the mechanisms by which SDC-1 participates in the pathogenesis of liver diseases, as well as its potential diagnostic and therapeutic applications. This review is expected to lay the foundation for further therapeutic strategies to target SDC-1 in liver diseases.

Pyroptosis has become a noteworthy area of focus in recent years due to its association with inflammatory diseases. Pyroptosis is a type of programmed cell death accompanied by an inflammatory response, and the discovery of the gasdermin family has expanded the study of pyroptosis. The primary characteristics of pyroptosis include cell expansion, membrane penetration, and the ejection of cell contents. In healthy physiology, pyroptosis is an essential part of the host's defence against pathogen infection. Excessive Pyroptosis, however, can lead to unchecked and persistent inflammatory responses, including the emergence of inflammatory diseases. More precisely, gasdermin family members have a role in the creation of membrane holes during pyroptosis, which leads to cell lysis. It is also related to how pro-inflammatory intracellular substances, including IL-1, IL-18, and High mobility group box 1 (HMGB1), are used. Two different signalling pathways, one of which is regulated by caspase-1 and the other by caspase-4/5/11, are the primary causes of pyroptosis. Cardiovascular diseases are often associated with cell death and acute or chronic inflammation, making this area of research particularly relevant. In this review, we first systematically summarize recent findings related to Pyroptosis, exploring its characteristics and the signalling pathway mechanisms, as well as various treatment strategies based on its modulation that has emerged from the studies. Some of these strategies are currently undergoing clinical trials. Additionally, the article elaborates on the scientific evidence indicating the role of Pyroptosis in various cardiovascular diseases. As a whole, this should shed insight into future paths and present innovative ideas for employing Pyroptosis as a strong disease-fighting weapon.

Proteolysis Targeting Chimeras (PROTACs) technology has emerged as a promising strategy for the treatment of undruggable therapeutic targets. Researchers have invested a great effort in developing druggable PROTACs; however, the problems associated with PROTACs, including poor solubility, metabolic stability, cell permeability, and pharmacokinetic profile, restrict their clinical utility. Thus, there is a pressing need to expand the size of the armory of PROTACs which will escalate the chances of pinpointing new PROTACs with optimum pharmacokinetic and pharmacodynamics properties. N- heterocycle is a class of organic frameworks that have been widely explored to construct new and novel PROTACs. This review provides an overview of recent efforts of medicinal chemists to develop N-heterocycle-based PROTACs as effective cancer therapeutics. Specifically, the recent endeavors centred on the discovery of PROTACs have been delved into various classes based on the E3 ligase they target (MDM2, IAP, CRBN, and other E3 ligases). Mechanistic insights revealed during the biological assessment of recently furnished Nheterocyclic- based PROTACs constructed via the utilization of ligands for various E3 ligases have been discussed.

Despite recent treatment advancements, breast cancer remains a life-threatening disease. Although treatment is successful in the early stages, a significant proportion of individuals with breast cancer eventually experience a recurrence of the disease. Breast tumour recurrence poses a significant medical issue. Despite tumours being a primary cause of mortality, there remains a limited understanding of the fundamental mechanisms underlying tumour recurrence. The majority of the time, after surgery or medical treatment, this metastatic disease manifests itself after the disease is undiagnosed for a considerable amount of time. This phenomenon is commonly referred to as a relapse or recurrence. Metastatic breast cancer has the potential to recur at varying intervals, ranging from a few months to several decades following the initial diagnosis and treatment. This article aimed to summarise the primary causes of breast cancer recurrence and highlight the key issues that need to be addressed in order to effectively decrease the mortality rate among breast cancer patients. This article discusses various therapeutic approaches currently employed and emerging treatment strategies that hold the potential for the complete cure of cancer.