Search results for "Drug repositioning"
showing 10 items of 26 documents
β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project
2016
β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changin…
Cancer therapy and treatments during COVID-19 era
2020
The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disea…
From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy.
2017
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteeth…
Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology.
2019
Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, a…
Repurposing of artemisinin-type drugs for the treatment of acute leukemia.
2020
Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold …
Repurposing of Drugs Targeting YAP-TEAD Functions
2018
Drug repurposing is a fast and consolidated approach for the research of new active compounds bypassing the long streamline of the drug discovery process. Several drugs in clinical practice have been reported for modulating the major Hippo pathway’s terminal effectors, namely YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional enhanced associate domains), which are directly involved in the regulation of cell growth and tissue homeostasis. Since this pathway is known to have many cross-talking phenomena with cell signaling pathways, many efforts have been made to understand its importance in oncology. Moreover, this could be rele…
Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells
2017
AbstractWe have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin’s effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding…
Drugs Polypharmacology by in Silico Methods: New Opportunities in Drug Discovery
2016
Background Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug dis…
Myotonic dystrophy type 1 drug development: A pipeline toward the market
2021
Highlights • Myotonic dystrophy, a neuromuscular disease, affects at least around half a million people worldwide. • Close to two dozen preclinical and clinical drug development programs active. • Drugs encompass new chemical entities, repurposing, oligonucleotide, and gene therapy. • Tideglusib, mexiletine, and metformin are close to reaching marketing authorization.
Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma
2021
A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…