Scaffold hopping has emerged as a practical tactic to enrich the synthetic bank of small molecule antitumor agents. Specifically, it enables the chemist to refine the lead compound's pharmacodynamic, pharmacokinetic, and physiochemical properties. Scaffold hopping opens up fresh molecular territory beyond established patented chemical domains.

G-quadruplexes (G4s) are secondary structures formed in guanine-rich regions of nucleic acids (both DNA and RNA). G4s are significantly enriched at regulatory genomic regions and are associated with important biological processes ranging from telomere homeostasis and genome instability to transcription and translation. Importantly, G4s are related to health and diseases such as cancer, neurological diseases, as well as infections with viruses and microbial pathogens. Increasing evidence suggests the potential of G4s for designing new diagnostic and therapeutic strategies although in vivo studies are still at early stages.

Mapping the interactions between pharmaceutical compounds and their molecular targets is a fundamental aspect of drug discovery and repurposing. Drug-target interactions are important for elucidating mechanisms of action and optimizing drug efficacy and safety profiles. Several computational methods have been developed to systematically predict drug-target interactions. However, computational and experimental validation of the drug-target predictions greatly vary across the studies.

Neuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions.

The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored.

Artificial intelligence (AI) is exhibiting tremendous potential to reduce the massive costs and long timescales of drug discovery. There are however important challenges currently limiting the impact and scope of AI models.

Targeting the enzyme L-Arginine:glycine amidinotransferase (AGAT) to reduce the formation of guanidinoacetate (GAA) in patients with guanidinoacetate methyltransferase (GAMT) deficiency, we attempted to identify drugs for repurposing that reduce the expression of AGAT via transcriptional inhibition.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.

For the past two decades, virtual screening (VS) has been an efficient hit finding approach for drug discovery. Today, billions of commercially accessible compounds are routinely screened, and many successful examples of VS have been reported. VS methods continue to evolve, including machine learning and physics-based methods.

Gefapixant, a P2X 3 receptor antagonist, shows considerable potential in managing refractory or unexplained chronic cough. Clinical trials have consistently demonstrated its efficacy in significantly reducing cough frequency and alleviating associated symptoms. However, its adverse effect profile, particularly taste disturbances such as dysgeusia and hypogeusia, the incidence of which is dose-dependent, poses a significant challenge to patient compliance and overall treatment satisfaction.

Targeted protein degradation (TPD) has emerged as an innovative therapeutic strategy through selective degradation of specific proteins by harnessing the cellular ubiquitin-proteasome system (UPS), which involves over 600 E3 ubiquitin ligases. Recent proteome profiling reported tumor-specific E3 ligases in human. Development of those tumor-specific E3 ligase ligands would provide a solution for tumor-specific TPD for effective cancer treatment.

Aptamers refer to short ssDNA/RNA sequences that target small molecules, proteins, or cells. Aptamers have significantly advanced diagnostic applications, including biosensors for detecting specific biomarkers, state-of-the-art imaging, and point-of-care technology. Molecular computation helps identify aptamers with high-binding affinity, enabling high-throughput screening, predicting 3D structures, optimizing aptamers for improved stability, specificity, and complex target interactions.

This review encapsulates the recent strides in the development of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, focusing on the novel structural designs that promise to overcome limitations of existing therapies, such as drug resistance and toxicity.

Cinnamic acid is a privileged scaffold for the design of biologically active compounds with putative anticancer potential, following different synthetic methodologies and procedures. Since there is a need for the production of potent anticancer, cinnamate moiety can significantly contribute in the design of new and more active anticancer agents.

Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD.

Myeloproliferative neoplasms (MPNs) are rare hematopoietic disorders driven by mutations in the JAK-STAT signaling pathway genes. While JAK2 inhibitors have transformed MPN treatment, they do not eliminate the malignant clone or prevent disease progression in most patients. This limitation underscores the need for more effective therapies.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness.