Drug-drug cocrystals: Opportunities and challenges.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC8261079 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Drug repositioning is defined as a process to identify a new application for drugs. This approach is critical as it takes advantage of well-known pharmacokinetics, pharmacodynamics, and toxicity profiles of the drugs; thus, the chance of their future failure decreases, and the cost of their development and the required time for their approval are reduced. Anthelmintics, which are antiparasitic drugs, have recently demonstrated promising anticancer effects in vitro and in vivo. This literature review focuses on the potential of anthelmintics for repositioning in the treatment of cancers. It also discusses their pharmacokinetics and pharmacodynamics as antiparasitic drugs, proposed anticancer mechanisms, present development conditions, challenges in cancer therapy, and strategies to overcome these challenges.
| S-EPMC8180459 | biostudies-literature
Project description:Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be "cured" of their disease, and 5-year event-free survival exceeds 80%. However, for patients surviving their malignancy, therapy-related long-term adverse effects are severe, with an estimated 50% having chronic life-threatening toxicities related to therapy in their fourth or fifth decade of life. While overall intensive therapy with cytotoxic agents continues to reduce cancer-related mortality, new understanding of the molecular etiology of many childhood cancers offers an opportunity to redirect efforts to develop effective, less genotoxic therapeutic options, including agents that target oncogenic drivers directly, and the potential for use of agents that target the tumor microenvironment and immune-directed therapies. However, for many high-risk cancers, significant challenges remain.
| S-EPMC6768308 | biostudies-literature
Project description:Significance: Chronic wounds remain a significant public health problem. Alterations in normal physiological processes caused by aging or diabetes lead to impaired tissue repair and the development of chronic and nonhealing wounds. Understanding the unique features of the wound environment will be required to develop new therapeutics that impact these disabling conditions. New drug-delivery systems (DDSs) may enhance current and future therapies for this challenging clinical problem. Recent Advances: Historically, physical barriers and biological degradation limited the efficacy of DDSs in wound healing. In aiming at improving and optimizing drug delivery, recent data suggest that combinations of delivery mechanisms, such as hydrogels, small molecules, RNA interference (RNAi), as well as growth factor and stem cell-based therapies (biologics), could offer exciting new opportunities for improving tissue repair. Critical Issues: The lack of effective therapeutic approaches to combat the significant disability associated with chronic wounds has become an area of increasing clinical concern. However, the unique challenges of the wound environment have limited the development of effective therapeutic options for clinical use. Future Directions: New platforms presented in this review may provide clinicians and scientists with an improved understanding of the alternatives for drug delivery in wound care, which may facilitate the development of new therapeutic approaches for patients.
| S-EPMC4742986 | biostudies-other
Project description:Macromolecules (proteins/peptides) have the potential for the development of new therapeutics. Due to their specific mechanism of action, macromolecules can be administered at relatively low doses compared with small-molecule drugs. Unfortunately, the therapeutic potential and clinical application of macromolecules is hampered by various obstacles including their large size, short in vivo half-life, phagocytic clearance, poor membrane permeability and structural instability. These challenges have encouraged researchers to develop novel strategies for effective delivery of macromolecules. In this review, various routes of macromolecule administration (invasive/noninvasive) are discussed. The advantages/limitations of novel delivery systems and the potential role of nanotechnology for the delivery of macromolecules are elaborated. In addition, fabrication approaches to make nanoformulations in different shapes and sizes are also summarized.
| S-EPMC5565796 | biostudies-other
Project description:Despite many advances in medical therapy for pulmonary arterial hypertension (PAH) over the past 20 years, long-term survival is still poor. Novel therapies which target the underlying pathology of PAH and which could be added to current vasodilatory therapies to halt disease progression and potentially reverse pulmonary vascular remodeling are highly sought after. Given the high attrition rates, substantial costs, and slow pace of new drug development, repositioning of "old" drugs is increasingly becoming an attractive path to identify novel treatment options, especially for a rare disease such as PAH. We here summarize the limitations of current PAH therapy, the general concept of repurposing and repositioning, success stories of approved repositioned drugs in PAH as well as novel repositioned drugs that show promise in preclinical models of pulmonary hypertension (PH) and are currently tested in clinical trials. We furthermore discuss various data-driven as well as experimental approaches currently used to identify repurposed drug candidates and review challenges for the "repositioning community" with regards to funding and patent and regulatory considerations, and to illustrate opportunities for collaborative solutions for drug repositioning relevant to PAH.
| S-EPMC6852366 | biostudies-literature
Project description:The use of targeted small-molecule therapeutics and immunotherapeutics has been limited to date in pediatric oncology. Recently, the number of pediatric approvals has risen, and regulatory initiatives in the United States and Europe have aimed to increase the study of novel anticancer therapies in children. Challenges of drug development in children include the rarity of individual cancer diagnoses and the high prevalence of difficult-to-drug targets, including transcription factors and epigenetic regulators. Ongoing pediatric adaptation of biomarker-driven trial designs and further exploration of agents targeting non-kinase drivers constitute high-priority objectives for future pediatric oncology drug development. SIGNIFICANCE: Increasing attention to drug development for children with cancer by regulators and pharmaceutical companies holds the promise of accelerating the availability of new therapies for children with cancer, potentially improving survival and decreasing the acute and chronic toxicities of therapy. However, unique approaches are necessary to study novel therapies in children that take into account low patient numbers, the pediatric cancer genomic landscape and tumor microenvironment, and the need for pediatric formulations. It is also critical to evaluate the potential for unique toxicities in growing hosts without affecting the pace of discovery for children with these life-threatening diseases.
| S-EPMC7933059 | biostudies-literature
Project description:Fibrodysplasia ossificans progressiva (FOP) is an ultrarare congenital disease that progresses through intermittent episodes of bone formation at ectopic sites. FOP patients carry heterozygous gene point mutations in activin A receptor type I ACVR1, encoding the bone morphogenetic protein (BMP) type I serine/threonine kinase receptor ALK2, termed activin receptor-like kinase (ALK)2. The mutant ALK2 displays neofunctional responses to activin, a closely related BMP cytokine that normally inhibits regular bone formation. Moreover, the mutant ALK2 becomes hypersensitive to BMPs. Both these activities contribute to enhanced ALK2 signalling and endochondral bone formation in connective tissue. Being a receptor with an extracellular ligand-binding domain and intrinsic intracellular kinase activity, the mutant ALK2 is a druggable target. Although there is no approved cure for FOP yet, a number of clinical trials have been recently initiated, aiming to identify a safe and effective treatment for FOP. Among other targeted approaches, several repurposed drugs have shown promising results. In this review, we describe the molecular mechanisms underlying ALK2 mutation-induced aberrant signalling and ectopic bone formation. In addition, we recapitulate existing in vitro models to screen for novel compounds with a potential application in FOP. We summarize existing therapeutic alternatives and focus on repositioned drugs in FOP, at preclinical and clinical stages.
| S-EPMC7922784 | biostudies-literature
Project description:Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines.We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of 'translational research'. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from 'bench to bedside and back again') with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease.
| S-EPMC4715274 | biostudies-literature
Project description:[Formula: see text] Fundamental processes in living cells are largely controlled by macromolecular interactions and among them, protein-protein interactions (PPIs) have a critical role while their dysregulations can contribute to the pathogenesis of numerous diseases. Although PPIs were considered as attractive pharmaceutical targets already some years ago, they have been thus far largely unexploited for therapeutic interventions with low molecular weight compounds. Several limiting factors, from technological hurdles to conceptual barriers, are known, which, taken together, explain why research in this area has been relatively slow. However, this last decade, the scientific community has challenged the dogma and became more enthusiastic about the modulation of PPIs with small drug-like molecules. In fact, several success stories were reported both, at the preclinical and clinical stages. In this review article, written for the 2014 International Summer School in Chemoinformatics (Strasbourg, France), we discuss in silico tools (essentially post 2012) and databases that can assist the design of low molecular weight PPI modulators (these tools can be found at www.vls3d.com). We first introduce the field of protein-protein interaction research, discuss key challenges and comment recently reported in silico packages, protocols and databases dedicated to PPIs. Then, we illustrate how in silico methods can be used and combined with experimental work to identify PPI modulators.
| S-EPMC4160817 | biostudies-literature
Project description:Cancer is a class of disorder characterized by anomalous growth of cells escalating in an uncontrolled way. Among all the cancers, treatment of cancerous brain tumors has been a tough challenge for the research scientists. Moreover, the absence of early-stage symptoms delays its diagnosis, consequently worsening its severity. Conventional treatments such as surgery, radiation, and chemotherapy are still linked with several limitations. The therapeutic effect of most of the anticancer drugs is highly restricted by their inability to pass the blood-brain barrier, low solubility, limited therapeutic window, and so on. Alarming incidences of brain cases associated with low survival rate across the globe coupled with the inefficiency of current treatment strategies have forced the formulation scientists to investigate nanotechnology-based advanced therapeutic approaches to tackle the disease. Various nanoplatforms such as polymeric nanoparticles (NPs), nanoliposomes, dendrimers, carbon nanotubes, and magnetic NPs have been reported in the past years to improve the drug administration into brain tumor cells and to minimize their off-target distribution for lesser side effects and better treatment outcomes. The review presents updated information on the nanocarrier-based drug delivery systems reported in the past few years for the treatment of brain tumor along with new advancements in this field. It also throws some light on the recent challenges faced in the practical field for the successful clinical translation of such nanodrug carriers along with a discussion on the future prospects.
| S-EPMC8291110 | biostudies-literature