Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

Using Data to Improve Healthcare: A Case Study of Pancreatic Enzyme Replacement in Pancreatic Cancer.

Objectives: In the UK, guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. In 2023, we published a national audit of PERT which showed suboptimal prescribing and wide regional variation in England. The aim of this manuscript was to describe how we used the PERT audit to drive improvements in healthcare.

Effective management of Colles fracture using Murivenna and Abha Guggulu - A case report.

Colles fracture is the commonest fracture encountered in orthopedic practice that demands prompt therapeutic intervention, and adequate follow-up to ensure complete healing. Various types of fractures, methods of reduction, and healing have been explained in the classical Ayurveda texts. These techniques are scientific and time-tested.

Optimization of a High-Throughput Cell-Based Screening Strategy to Identify Small-Molecule Inhibitors of IL-23 Signaling.

Interleukin-23 (IL-23) is a key cytokine implicated in the pathogenesis of autoimmune disorders, including psoriasis and ulcerative colitis. Although targeted IL-23 antibody therapeutics are used clinically, there are no small-molecule therapeutics that selectively inhibit IL-23 signaling. To address this gap, we developed a high-throughput screening strategy employing an IL-23-responsive cell-based luciferase reporter gene assay as the primary screen, with cellular cytotoxicity and off-target counter screening assays to identify IL-23 pathway-specific inhibitors.

An Analysis of Different Components of a High-Throughput Screening Library.

Since many projects at pharmaceutical organizations get their start from a high-throughput screening (HTS) campaign, improving the quality of the HTS deck can improve the likelihood of discovering a high-quality lead molecule that can be progressed to a drug candidate. Over the past decade, Janssen has implemented several strategies for external compound acquisition to augment the screening deck beyond the chemical space and number of molecules synthesized for internal projects. In this report, we analyzed the performance of each of those compound collections in the screening campaigns performed internally within Janssen during the last five years.