Drug Discovery Today最新文献

The global oncology drug pipeline is characterized by a tension between the diversification of novel targets and a persistent concentration on a few validated ones. Our analysis of 5127 drugs against 1603 targets categorizes entities as 'proven' (10.4%), 'in development' (53.6%), or 'not progressing well' (36.1%). While single-target agents dominate, dual-target strategies, driven by bispecific antibodies, are the fastest-growing approach. The top 20 proven targets attract over 50 drugs each. Small molecules remain prevalent, but novel modalities are expanding. Clinical validation of a novel target requires a median of 8.0 years with a 22.3% success rate. The USA and China drive 62.7% of global development, with the USA leading in first-in-class (FIC) innovation and China's role increasing since 2020.

Target product profiles (TPPs) guide medical product development by defining desired characteristics to address specific diseases or needs. By specifying safety, efficacy, usability, access, and differentiation, TPPs help to prioritize resources, surface challenges early, and reduce failure risk. Although common in drug development, TPPs are less often applied to substance use disorders (SUDs). This article shows how an SUD TPP should balance regulatory feasibility, clinical relevance, and commercial viability. We offer an example TPP for an aspirational opioid use disorder drug to test differentiation and market assumptions against existing therapies. TPPs focus attention beyond mechanistic novelty, clarifying distinct product attributes. Thoughtful TPP design increases the chance that a product will be safe, effective, accessible, reimbursable, and equitably distributable.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections and hospitalizations among vulnerable populations, such as children, older adults, and individuals with weakened immune systems, often causing seasonal epidemics. Although current prophylactics, such as palivizumab, nirsevimab, and clesrovimab, which target the RSV F protein, have enhanced early protection, more effective options with broader impact and longer-lasting efficacy are needed. In response to ongoing research efforts to develop new treatments for RSV, nanobodies have emerged as a promising option. Therefore, in this review, we discuss available therapies and explore the potential of nanobodies in treating RSV, with particular emphasis on the importance of polybodies [polyspecific and polyvalent antibodies (PsAbs and PvAbs)] in managing RSV infections.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease that causes inflammation and scarring around the lung alveoli. This scarring is called fibrosis and leads to breathing difficulties in patients. The treatment for PF is currently limited to two drugs: nintedanib and pirfenidone. Their use is restricted owing to poor bioavailability and a few contraindications. Biotechnological advancements are leading to the investigation of targeted systems aimed at reversing alveolar damage and alleviating PF. This review provides key insights on biotechnology-based advancements for PF, namely monoclonal antibodies, peptides, nucleic acids and stem cell therapy. We also underscore the obstacles and prospective developments in biotechnology-derived therapeutics for PF.

Seizures are the hallmark of treatment-resistant epilepsy and are also a frequent adverse event in drug safety testing. Here we present a critical evaluation of new approach methodologies (NAMs) in epilepsy research and seizure liability. Specifically, recent data have shown that seizure can be profiled using an in vitro seizure liability assay (iSLA) comprising a microelectrode array (MEA) of human induced pluripotent stem cell (iPSC) neurons coupled with a human ion channel panel. Adverse outcome pathways (AOPs) also offer a powerful NAM framework to map how key events can lead to an adverse outcome such as seizure. These NAMs offers an innovative approach to antiseizure medication research as well as to seizure risk testing in drug discovery and development.