Current drug targets最新文献

B-cell lymphoma-2 (BCL-2) plays a key role in regulating apoptosis. Venetoclax (VEN), a BCL-2 inhibitor, has been approved for the treatment of a variety of haematologic malignancies. VEN is primarily metabolized by CYP3A, and a variety of factors (such as CYP3A inhibitors, as well as food and hepatic functions) have been reported to significantly influence the metabolic process. There is significant interindividual variability in VEN plasma concentrations, and studies have shown that its exposure levels are correlated with efficacy, although the relationship with adverse effects remains controversial. The value of applying of therapeutic drug monitoring (TDM) in individualized VEN therapy has been confirmed by some studies, but the optimal therapeutic window for different malignancies is still unclear. This review summarizes the pharmacokinetic characteristics, along with the factors influencing VEN pharmacokinetics, drug-drug interactions, and advancements in TDM research on VEN, aiming to provide a theoretical basis for TDM-guided individualized therapy.

Introduction/objective: Heterocyclic molecules, a mainstay of contemporary medicinal chemistry, are essential in developing antibacterial and anticancer treatments. Their distinct structural features-one or more heteroatoms within the ring-allow for a wide range of biological activities. With a focus on their modes of action and insights into the structure-activity relationship (SAR), this study examines the therapeutic uses of heterocyclic compounds in antibacterial, antifungal, antiviral, and anticancer treatments.

Methods: The review uses search engines like PubMed and Google Scholar, with a preference for English as the major language, to gather and analyse recent research on the antibacterial and anticancer applications of diverse heterocyclic compounds.

Results: It has been discovered that heterocyclic chemicals are useful in blocking microbial enzymes, including DNA gyrase and the machinery involved in protein synthesis. Heterocyclic compounds such as benzimidazoles, quinolines, and acridines have demonstrated noteworthy efficacy in cancer therapy through their targeting of tubulin inhibition, DNA intercalation, and signalling pathways like PI3K/Akt/mTOR and MAPK. The pharmacological characteristics of these compounds were improved by the addition of electron-withdrawing groups, halogenation, and heteroatom replacements, according to SAR investigations.

Conclusion: Heterocyclic compounds have great promise for antibacterial and anticancer treatments. They are crucial in drug development because of their structural flexibility, which enables the targeted suppression of vital biological processes. The effectiveness of heterocyclic compounds will continue to be improved by ongoing advancements in drug design and SAR optimization, opening new possibilities for the creation of more potent and selective medicinal treatments.

Matrix metalloproteinase-9, also known as MMP-9, gelatinase B, or 92 kDa type IV collagenase, is an enzyme that belongs to the matrix metalloproteinase (MMP) family. It is involved in the remodeling of the extracellular matrix in various physiological and pathological processes. MMPs are expressed in low, tightly regulated concentrations; their overexpression or dysregulation can lead to diseases, including cancer. MMP-9 is increasingly recognized as a significant drug target in cancer therapy due to its involvement in tumorigenesis, including processes like cell migration, angiogenesis, and pro-apoptotic and anti-apoptotic activities. Despite MMP-9's significance as a cancer target, developing effective inhibitors remains challenging due to MMP structural similarities. Utilizing MMP-9 as a cancer biomarker could advance cancer diagnosis, prognosis, disease monitoring, recurrence prediction, and other procedures. Biosensors are emerging as pivotal tools in cancer diagnosis and treatment, leveraging their ability to detect specific biomarkers associated with various cancers. Recent advancements have led to the development of both cleavage-based and non-cleavage-based biosensors that enable rapid and sensitive analysis at clinically relevant concentrations of biomarkers while allowing specificity and low detection limits, enhancing point-of-care diagnostics. The cleavage-based biosensors leverage the enzymatic activity of MMP-9, utilizing substrates that are specifically cleaved by MMP-9, while the non-cleavage- based biosensors employ affinity methods, such as antibodies and aptamers for detection. The present review aims to evaluate the role of MMP-9 as a significant biomarker in cancer and its detection through innovative biosensor technologies, while exploring its involvement in various cancer- related processes. This review discusses the significance of MMP-9 in cancer progression, highlighting clinical trials that assess MMP-9 inhibitors as potential therapeutic agents to halt metastatic spread. Furthermore, MMP-9 is detected via biosensors, and insights into the translational potential of MMP-9 both as a biomarker for early cancer detection and a viable target for therapeutic intervention are provided, ultimately contributing to improved patient outcomes in oncology.

Delayed diagnosis and limited treatment options make ovarian cancer difficult to treat. This paper examines the growing role of Carbon Dots (CDs) in ovarian cancer diagnosis and treatment. Photoluminescence and biocompatibility make CDs ideal for biomedical use. We emphasize their ability to improve fluorescence and molecular imaging in imaging and diagnostics. We also demonstrate the efficacy of carbon dots in targeted drug delivery systems in overcoming drug resistance and improving therapeutic outcomes. Photodynamic and photothermal therapies are used to show that CDs can treat hypoxic ovarian cancer tumours. We also discuss CD safety issues and constraints, emphasising the need for thorough assessments and fine-tuning. Future research focuses on personalised medicine and CD integration with other therapies. This text concludes by discussing CDs' clinical use and the challenges of production and regulatory approval. CDs can improve ovarian cancer diagnosis and treatment, improving patient outcomes and survival.

Treating neurological illnesses is challenging because the blood-brain barrier hinders therapeutic medications from reaching the brain. Recent advances in polymeric nanocarriers (PNCs), which improve medication permeability across the blood-brain barrier, may influence therapy strategies for neurological diseases. PNCs have several ways to deliver medications to the nervous system. This review article provides a summary of the parts and manufacturing methods involved in making PNCs. Additionally, it highlights the elements that result in PNCs having enhanced blood-brain barrier penetration. A combination of passive and active targeting strategies is used by PNCs intended to overcome the blood-brain barrier. Among these are micellar structures, nanogels, nanoparticles, cubosomes, and dendrimers. These nanocarriers, which are functionalized with certain ligands that target BBB transporters, enable the direct delivery of drugs to the brain. Mainly, the BBB prevents medications from entering the brain. Understanding the BBB's physiological and anatomical characteristics is necessary to get over this obstacle. Preclinical and clinical research demonstrates the safety and effectiveness of these PNCs, and their potential use in the treatment of neurological illnesses, including brain tumors, Parkinson's disease, and Alzheimer's disease, is discussed. Concerns that PNCs may have about their biocompatibility and possible toxicity are also covered in this review article. This study examines the revolutionary potential of PNCs in CNS drug delivery, potential roadblocks, ongoing research, and future opportunities for PNC design progress. PNCs open the door to more focused and efficient treatment for neurological illnesses by comprehending the subtleties of BBB penetration.

Background: In organ-specific therapy, artificial intelligence (AI) is primarily used to improve surgical planning through image analysis, predict post-transplant outcomes, personalize treatment plans based on patient data, optimize organ allocation logistics, and donor-recipient precision mapping for organs to improve transplants. Furthermore, all these applications ultimately lead to better patient outcomes and enhanced organ therapy.

Objective: This review aims to examine the revolutionary effects of AI in some key healthcare fields, such as nanomedicine, cancer treatment, clinical applications, and organ-specific delivery.

Methods: This review article discusses in detail the role of AI in nanomedicine, cancer therapy, clinical applications, organ-specific delivery (e.g., cardiovascular, gastroenterology, kidney, liver, lung, ophthalmology, skin, etc.), diagnosis, and radiotherapy. In addition, it also discusses limitations and challenges of AI in healthcare.

Results: AI-based clinical translation has potential but faces challenges like artifact vulnerability, ethical and legal considerations, and security measures. Restrictive data-use policies may hinder accurate analysis. Regulations and collaboration with data-sharing mechanisms could overcome barriers.

Conclusion: AI is being utilized in organ-specific therapy to enhance donor-recipient matching, surgical planning, post-transplant outcomes prediction, and personalized treatment plans by analyzing patient data.

Lipidomics, a cutting-edge branch of metabolomics provides a comprehensive understanding of the lipidome and its alterations in cellular and systemic processes. In Breast Cancer (BC), a highly heterogeneous disease, lipidomics has emerged as a pivotal tool for exploring metabolic reprogramming, tumor progression, and therapeutic resistance. This review highlights the intricate relationship between lipid metabolism and breast cancer, with a focus on subtype-specific lipid dependencies, oxidative stress, and ferroptosis. Technological advancements, such as mass spectrometry and chromatography, have enabled precise profiling of lipid alterations, revealing distinct lipid signatures across breast cancer subtypes. Key enzymes like acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), along with lipid regulators like PPARγ, have been identified as central players in lipid-driven tumorigenesis. Lipidomic studies offer the potential for biomarker discovery and the development of lipid-targeted therapies. Despite challenges in standardization and integration with other omics approaches, lipidomics is poised to revolutionize breast cancer diagnostics and therapeutics, providing novel insights into the metabolic underpinnings of this complex disease.

Digital twin technology has emerged as a breakthrough development in healthcare, providing personalised transdermal drug delivery systems for chronic pain treatment. Digital twins provide accurate, customised therapy to enhance therapeutic outcomes and reduce risks by combining patient-specific computational models. This article aims to explore the applicability of digital twin technology in improving the transdermal delivery of drugs for successful chronic pain management. It is enabling personalised treatment through patient-specific simulations. By integrating physiological data with computational models, digital twins optimise drug absorption, patch application, and dosage adjustments in real-time, enhancing therapeutic outcomes while minimising side effects. Recent advancements highlight improvements in fentanyl patch optimisation, site-specific drug delivery, and thermally controlled systems. However, challenges such as ethical concerns, data security, and standardisation need to be addressed. Future research should focus on integrating AI and IoT to refine digital twin applications in precision medicine. It can be concluded from the findings of various studies that digital twin technology offers a promising future for precise and individualised transdermal drug delivery in chronic pain, paving the way for safer and more effective therapeutic interventions.

Introduction: Parkinson's disease (PD) is a persistent neurodegenerative condition marked by rising global rates of disability and mortality, warranting the need for new treatment options. The present investigation evaluated the protective effects of novel glitazones C7 and C25 against rotenone-induced PD in a mouse model.

Methods: Molecular docking using Discovery Studio and molecular dynamics simulations were employed to evaluate the binding ability of C7 and C25 to the PGC-1α target protein. Pharmacokinetic evaluations of C7 and C25 were performed against the standard pioglitazone in the rats model, and acute toxicity assessments were conducted following OECD guidelines 423. The neuroprotective effects of C7 were tested in a rotenone-induced mouse model of PD at doses of 10, 20, and 30 mg/kg body weight. Behavioral studies, including locomotor activity, grip strength, and catalepsy, as well as biochemical analyses such as endogenous antioxidant levels and AChE levels, were assessed.

Results: The novel compound C7 demonstrated good binding and simulation at the PGC-1α target protein. The kinetic profile of C7 was found to be good when compared to C25. Both the novel glitazones were safe at 300 mg/kg body weight when tested for oral acute toxicity. The novel compound C7 effectively alleviated symptoms related to rotenone-induced PD, demonstrating its promise as a therapeutic candidate.

Discussion: In the rotenone-induced mouse model, compound C7 exhibited a promising anti-PD effect by attenuating oxidative stress and increasing muscular activity, which merits further investigations.

Conclusion: Additional research using various induction models, along with further investigation of cellular and molecular markers in larger animal studies, is needed to validate these findings.

Despite their hazardous nature, snake venoms hold immense potential for the development of novel therapies. This summary delves into the key aspects of snake venom research, focusing on their significance as targets for neutralization, their utility as novel drugs, the application of in silico studies, and future prospects with nanotechnology. Significance of Snake Venom: Snake venom harbors a rich diversity of toxic proteins with a wide range of biological activities. Its importance lies in the possibility of neutralizing its detrimental effects and exploring its therapeutic potential for diverse ailments. Venom Neutralization: The development of more effective and specific antivenoms is crucial for treating snakebites, particularly in regions with a high prevalence of accidents. Molecular-level venom studies are essential for identifying novel targets for the development of more efficacious antivenoms. Venom as a Source of Novel Drugs: Proteins present in snake venom exhibit diverse pharmacological activities, including antithrombotic, anti-inflammatory, analgesic, and antimicrobial properties. Investigating these proteins can lead to the development of novel medications for various diseases. In silico Studies: Bioinformatics tools and molecular modelling can aid in the discovery of novel molecular targets in snake venom, accelerating the process of developing new drugs and therapies. Nanotechnology for Drug Delivery: Nanotechnology offers new possibilities for developing more efficient and targeted drug delivery systems, enhancing the safety and effectiveness of snake venom- based treatments. Snake venom research represents a promising area of inquiry with immense potential for the development of novel drugs and therapies. The integration of traditional and innovative techniques, such as in silico studies and nanotechnology, can accelerate this process and contribute to the advancement of public health.