As a high-metabolic-rate organ, the kidney exhibits metabolic reprogramming (MR) in various disease states. Given the 860.8 million cases of kidney disease worldwide in 2017, understanding the specific bioenergetic pathways involved and developing targeted interventions are vital needs. The reprogramming of metabolic pathways (glucose metabolism, amino acid metabolism, etc.) has been observed in kidney disease. Therapies targeting these specific pathways have proven to be an efficient approach for retarding kidney disease progression. In this review, we focus on potential pharmacological interventions targeting MR that have advanced through Phase III/IV clinical trials for the management of kidney disease and promising preclinical studies laying the groundwork for future clinical investigations.

Cryptides are a subfamily of bioactive peptides embedded latently in their parent proteins and have multiple biological functions. Cationic cryptides could be used as modern drugs in both infectious diseases and cancers because their mechanism of action is less likely to be affected by genetic mutations in the treated cells, therefore addressing a current unmet need in these two areas of medicine. In this review, we present the current understanding of cryptides, methods to mine them sustainably using available online databases and prediction tools, with a particular focus on their antimicrobial and anticancer potential, and their potential applicability in a clinical setting.

Pharmaceutical co-crystals represent a growing class of crystal forms in the context of pharmaceutical science. They are attractive to pharmaceutical scientists because they significantly expand the number of crystal forms that exist for an active pharmaceutical ingredient and can lead to improvements in physicochemical properties of clinical relevance. At the same time, machine learning is finding its way into all areas of drug discovery and delivers impressive results. In this review, we attempt to provide an overview of machine learning, deep learning and network-based recommendation approaches applied to pharmaceutical co-crystallization. We also present crystal structure prediction as an alternative to machine learning approaches.

The suitability of small molecules as oral drugs is often assessed by simple physicochemical rules, the application of ligand efficiency scores or by composite scores based on physicochemical compound properties. These rules and scores are empirical and typically lack mechanistic background, such as information on pharmacokinetics (PK). We introduce new types of Compound Quality Scores (CQS, specifically called dose scores and cmax scores), which explicitly include predicted or, when available, experimental PK parameters and combine these with on-target potency. These CQS scores are surrogates for an estimated dose and corresponding cmax and allow prioritizing of compounds within test cascades as well as synthesis. We demonstrate the complementarity and, in most cases, superior performance relative to existing efficiency metrics by project examples.

Medication adherence in pediatric patients is a key factor in drug development and dosage form design. High medication adherence is not only important to achieve the expected treatment effects but can also effectively reduce medical costs. It is an ongoing task to accurately identify differences in medication adherence between children and adults and analyze the factors related to pediatric medication adherence. This is necessary to guide the development of pediatric drugs. This review focuses on factors that influence medication adherence as well as pharmaceutical design strategies to improve adherence. Current and new dosage forms, new technologies, and new devices are comprehensively summarized in terms of their advantages and limitations.

Recently, targeted protein degradation technologies based on lysosomal pathways have been developed. Lysosome-based targeted protein degradation technology has a broad range of substrates and the potential to degrade intracellular and extracellular proteins, protein aggregates, damaged organelles and non-protein molecules. Thus, they hold great promise for drug R&D. This study has focused on the biogenesis of lysosomes, their basic functions, lysosome-associated diseases and targeted protein degradation technologies through the lysosomal pathway. In addition, we thoroughly examine the potential applications and limitations of this technology and engage in insightful discussions on potential avenues for future research. Our primary objective is to foster preclinical research on this technology and facilitate its successful clinical implementation.

Affinity selection mass spectrometry (AS-MS) has gained momentum in drug discovery. This review summarizes how this technology has slowly risen as a new paradigm in hit identification and its potential synergy with DNA encoded library technology. It presents an overview of the recent results on challenging targets and perspectives on new areas of research, such as RNA targeting with small molecules. The versatility of the approach is illustrated and strategic drivers discussed in terms of the experience of a small-medium CRO and a big pharma organization.

Current treatment strategies for triple-negative breast cancer (TNBC) are based upon conventional chemotherapy, immunotherapy, or a combination of both. The treatment regimen for chemotherapy is often a combination of two or more drugs, either dose dense or low dose for synergy. Anthracyclines, alkylating agents, antimicrotubule agents, and antimetabolites for early-stage TNBC; and antimetabolites, non-taxane microtubule inhibitors, and cross-linker platinums for late-stage TNBC are usually administered in the clinical setting. Newer options for patients with advanced TNBC, such as poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, have recently emerged for cases where surgery is not a viable option and the disease has metastasized. This review outlines the current trends in hypoxia-inspired treatment strategies for TNBC with a focus on clinical trials.

In the pharmaceutical industry, it is essential to ensure the safety and efficacy of medicinal products. Therefore a robust quality assurance framework is needed. This manuscript examines the impact of GAMP 5 and data integrity (DI) on quality assurance, while also highlighting the role of quality by design (QbD) principles. GAMP 5 is a widely used framework for validating automated systems that establishes quality assurance practices. DI guarantees the reliability of data collected throughout various stages of drug development. The integration of QbD principles promotes a systematic approach to development that emphasizes a deep understanding of critical quality attributes, risk management, and continuous improvement. With their implementation, organizations are able to meet regulatory requirements and provide safe medications to patients worldwide.

Certain mono-infections of influenza viruses and novel coronaviruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are significant threats to human health. Concurrent infections by influenza viruses and coronaviruses increases their danger. Influenza viruses have eight manipulations capable of assisting SARS-CoV-2 and other coronaviruses, and several of these manipulations, which are not specific to viruses, can also directly or indirectly boost dangerous secondary bacterial pneumonias. The influenza virus manipulations include: inhibiting transcription factors and cytokine expression; impairing defensive protein expression; increasing RNA viral replication; inhibiting defenses by manipulating cellular sensors and signaling pathways; inhibiting defenses by secreting exosomes; stimulating cholesterol production to increase synthesized virion infectivities; increasing cellular autophagy to assist viral replication; and stimulating glucocorticoid synthesis to suppress innate and adaptive immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. Teaser: Rapidly spreading multidrug-resistant respiratory bacteria, combined with influenza virus's far-reaching cellular defense manipulations benefiting evolving SARS-CoV-2 or other coronaviruses and/or respiratory bacteria, can enable more severe pandemics or co-pandemics.