Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant rep...
Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal...
Published in Chemmedchem
A successful screen performed within the European Lead Factory program, followed by docking studies, has resulted in compound 32 , a potent and selective N ‐(4‐benzamidino)‐oxazolidinone inhibitor of kallikrein‐related peptidase 6 (KLK6). Aberrant levels of this serine protease have been found in different malignancies and in neurodegenerative dise...
An increasing aging population poses a significant challenge to societies worldwide. A better understanding of the molecular, cellular, organ, tissue, physiological, psychological, and even sociological changes that occur with aging is needed in order to treat age-associated diseases. The field of aging research is rapidly expanding with multiple a...
Published in Current drug discovery technologies
In the presented work we successfully discovered several novel NQO1 inducers using the computational approaches. The phytochemical sulforaphane (SFN) is a potent inducer of carcinogen detoxication enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1) through the Kelch-like erythroid cell-derived protein with CNC homology[ECH]-associated protein 1 (K...
Published in ACS infectious diseases
The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will require compounds that can broadly inhibit these resistance-conferring isoforms. Using a structure-based approa...
Published in Seminars in cancer biology
A pre-eminent subtype of lung carcinoma, Non-small cell lung cancer accounts for paramount causes of cancer-associated mortality worldwide. Undeterred by the endeavour in the treatment strategies, the overall cure and survival rates for NSCLC remain substandard, particularly in metastatic diseases. Moreover, the emergence of resistance to classic a...
As antiviral drug resistance develops and new viruses emerge there is a pressing need to develop strategies to rapidly develop antiviral therapeutics. Here we use phospho-specific flow cytometry to assess perturbations of many different cellular signaling pathways during treatment with drug combinations that are highly effective in blocking Herpes ...
BACKGROUND:Over the past five years, as a public service to encourage and accelerate drug discovery for diseases of poverty, the Medicines for Malaria Venture (MMV) has released box sets of 400 compounds named the Malaria, Pathogen and Stasis Boxes. Here, we screened the Pathogen Box against the post-infective larvae (schistosomula) of Schistosoma ...
Published in Medicinal chemistry (Shariqah (United Arab Emirates))
New chemical agents that could combat increasing antibiotic resistance are urgently needed. In this mini-review, an old but highly relevant RNA sequence which is crucial for the continuation of bacterial life-cycle is covered. Some of the most significant advances of the last decade in sensing and targeting the bacterial rRNA A-site: a well-validat...
