Drug Discovery Today

The Allotrope Foundation (AF) started as a group of pharmaceutical companies, instrument, and software vendors that set out to simplify the exchange of data in the laboratory. After a decade of work, they released products that have found adoption in various companies. Most recently, the Allotrope Simple Model (ASM) was developed to speed up and widen the adoption. As a result, the Foundation has recently added chemical companies and, importantly, is reworking its business model to lower the entry barrier for smaller companies...

Human-centric methodologies like microphysiological systems and in silico methods have shown promise in addressing the limitations of animal models in understanding human biology and responding to public health priorities. However, the prevailing paradigm based on animal research persists. The article proposes a systemic thinking approach, endorsed by the OECD and the EU, as a tool to leverage innovation to reframe the issue and achieve transformative policies. By identifying the complex factors shaping method selection in basic and biomedical research, a simplified model is presented to illuminate the systemic nature of this decision-making process...

Design-Make-Test-Analyse (DMTA) is the discovery cycle through which molecules are designed, synthesised, and assayed to produce data that in turn are analysed to inform the next iteration. The process is repeated until viable drug candidates are identified, often requiring many cycles before reaching a sweet spot. The advent of artificial intelligence (AI) and cloud computing presents an opportunity to innovate drug discovery to reduce the number of cycles needed to yield a candidate. Here, we present the Predictive Insight Platform (PIP), a cloud-native modelling platform developed at AstraZeneca...

Master protocol designs such as umbrella and basket studies allow multiple compounds or multiple target populations to be evaluated simultaneously within a single protocol, and THEY have been widely adopted in oncology clinical trials. These novel designs can also be applied in other therapeutic areas, where they could have several benefits over conducting traditional randomized controlled trials. Here, we detail Pfizer's recent implementations of master protocol designs in inflammation and immunology clinical studies, focusing on the opportunities for cost and resource savings and how these designs can expedite the time required to bring new treatments to patients in need...

Liver cancer, the sixth most common cancer globally and the second-leading cause of cancer-related deaths, presents a critical public health threat. Diagnosis often occurs in advanced stages of the disease, aligning incidence with fatality rates. Given that established treatments, such as stereotactic body radiation therapy and transarterial radioembolization, face accessibility and affordability challenges, the emerging focus on cancer cell metabolism, particularly arginine (Arg) depletion, offers a promising research avenue...

The drug discovery and development process encompasses the interrogation of metabolites arising from the biotransformation of drugs. Here we look at why, when and how metabolites of small-molecule drugs are synthesised from the perspective of a specialist contract research organisation, with particular attention paid to projects for which regulatory oversight is relevant during this journey. To illustrate important aspects, we look at recent case studies, trends and learnings from our experience of making and identifying metabolites over the past ten years, along with with selected examples from the literature...

Despite successes with new drug approvals over the past two decades through conventional drug development approaches, many human diseases remain intractable to current therapeutic interventions. Possible barriers may be that the complexity of the target, and disease biology, are impervious to such conventional drug development approaches. The US National Institutes of Health hosted a workshop with the goal of identifying challenges and opportunities with alternative modalities for developing treatments across diseases associated with historically undruggable targets...

Drug-induced renal injury (DIRI) causes >1.5 million adverse events annually in the USA alone. Although standard biomarkers exist for DIRI, they lack the sensitivity or specificity to detect nephrotoxicity before the significant loss of renal function. In this study, we describe the creation of DIRIL - a list of drugs associated with DIRI and nephrotoxicity - from two literature datasets with DIRI annotation, confirmed using FDA drug labeling. DIRIL comprises 317 orally administered drugs covering all 14 anatomical, therapeutic and chemical (ATC) classification categories...

No abstract text is available yet for this article.

Pharmaceutical managers have been encouraged to look to acquisitions and alliances for innovation. However, the literature warns that the capacity of a company to 'absorb' new knowledge is limited. Here, we introduce corporate divestitures as a tool for freeing up managerial attention. We build a sample of 349 companies, which announced 1784 divestitures and filed 63523 patents, over a 15-year period. We show that innovating companies that divest more produce more and improved patents, and those that divest to create corporate focus also produce more breakthroughs...

This review highlights the transformative impact of microfluidic technology on personalized drug delivery. Microfluidics addresses issues in traditional drug synthesis, providing precise control and scalability in nanoparticle fabrication, and microfluidic platforms show high potential for versatility, offering patient-specific dosing and real-time monitoring capabilities, all integrated into wearable technology. Covalent conjugation of antibodies to nanoparticles improves bioactivity, driving innovations in drug targeting...

The objectives of drug R&D in China have shifted toward innovation and globalization, highlighting the ecological imperative to involve innovative partner-like academic research organizations (AROs). AROs are led by academic institutions and, when compared to contract research organizations (CROs), their strengths lie in promoting academic excellence, knowledge sharing, independence, collaborative networks and industry partnerships. Our desk-based analysis shows that although the service scope of Chinese AROs is similar to that of AROs in the US, they lack experience in broad service provision for innovative drugs, institution-institutional platforms and industry partnerships...

Cancer remains one of the most devastating diseases, necessitating innovative and precise therapeutic solutions. The emergence of 3D bioprinting has revolutionized the platform of cancer therapy by offering bespoke solutions for drug screening, tumor modeling, and personalized medicine. The utilization of 3D bioprinting enables the fabrication of complex tumor models that closely mimic the in vivo microenvironment, facilitating more accurate drug testing and personalized treatment strategies. Moreover, 3D bioprinting also provides a platform for the development of implantable scaffolds as a therapeutic solution to cancer...

The shortcomings of current approaches to treating cancer are driving the need for novel, innovative strategies that reduce the toxicity associated with chemotherapy and improve on the limited efficacy of immunotherapy. We believe that dual delivery of small interfering RNA (siRNA) via a suitable delivery system, with or without a relevant, additional, small-molecule therapeutic agent, will herald new era of treatment efficiency in cancer.

GPR52 is a highly conserved, brain-enriched, Gs/olf -coupled orphan G protein-coupled receptor (GPCR) that controls various cyclic AMP (cAMP)-dependent physiological and pathological processes. Stimulation of GPR52 activity might be beneficial for the treatment of schizophrenia, psychiatric disorders and other human neurological diseases, whereas inhibition of its activity might provide a potential therapeutic approach for Huntington's disease. Excitingly, HTL0048149 (HTL'149), an orally available GPR52 agonist, has been advanced into phase I human clinical trials for the treatment of schizophrenia...

Cell death plays a crucial part in the process of age-related macular degeneration (AMD), but its mechanisms remain elusive. Accumulating evidence suggests that ferroptosis, a novel form of regulatory cell death characterized by iron-dependent accumulation of lipid hydroperoxides, has a crucial role in the pathogenesis of AMD. Numerous studies have suggested that ferroptosis participates in the degradation of retinal cells and accelerates the progression of AMD. Furthermore, inhibitors of ferroptosis exhibit notable protective effects in AMD, underscoring the significance of ferroptosis as a pivotal mechanism in the death of retinal cells during the process of AMD...

Biotechnology and small pharma companies must recognize the opportunity presented by FDA Breakthrough Therapy Designation (BTD) to expedite drug development for serious conditions. This paper evaluates BTD economic and developmental impacts on such companies. Analysis of 29 BTD events from 2017 to 2022 revealed immediate share price boosts and improved drug approval rates, alongside faster development times. Yet, long-term share prices underperformed relative to the broader market, underscoring the persistent risks in pharma investments...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

There are many different approaches to drug discovery in academia, some of which are based broadly on the industrial model of discovering novel targets and then conducting screening within academic drug discovery centres to identify hit molecules. Here we describe our approach to drug discovery, which makes more efficient use of the capabilities and resources of the different stakeholders. Specifically, we have created a large portfolio of drug projects and conducted small amounts of derisking work to ensure projects are investment ready...