Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were −7.7, −6.3 and −5.7 kcal/mol, respectively. Collectively, 4k, 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k, 4m and 7x providing a promising treatment option for chemoresistant NSCLC.
Psychosis is a psychological disorder that causes an imbalance in social functioning, perception, and thought. Several genetic and environmental factors are in accordance with the progression of psychosis. Schizophrenia, severe depression, and bipolar disorder causes severe mental illness psychosis. Schizophrenia is a multisystem disorder that causes several immune dysfunctions such as abnormal levels of circulating cytokines. Bipolar disorder is associated with immune dysfunctions and increases the rate of inflammatory medical comorbidities, including cardiovascular disease, chronic infections, autoimmune disorders, and metabolic disorders. In psychosis, a single relapse occurs that causes the disability of facial expressions. Emotion processing deficit persists in the acute phase of schizophrenia and the symptomatic recovery. Furthermore, psychosis acts like an autoimmune disease that leads to CNS autoimmune and inflammatory diseases, like grave's diseases, multiple sclerosis, diabetes, systemic lupus erythematosus, autoimmune vasculatures, and sarcoidosis. This review deals with the genetic association in psychosis and the relation between psychosis and autoimmune disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.