Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: The son of sevenless (SOS) proteins are rat sarcoma virus nucleotide exchange factors that act as regulatory switches of the rat sarcoma virus (RAS) system through the conversion of the inactive guanosine diphosphate (GDP) bound RAS to the GTP-bound active form, thereby modulating numerous biological events. SOSs contribute in disease incidence and progression in numerous cancers. Currently, SOSs inhibiting strategies deemed a substantial interest in the fight against cancer.
Materials And Methods: To date, there are various SOS1 inhibitors in the clinical trials, however there are no reported SOS2 inhibitors so far. In this study, we explored the Enamine fragments library against SOS2 through the multidisciplinary computational analysis. Pharmacophore modelling based on the previously published SOS2 inhibitory fragments has shed light on the influential pharmacophoric features. Subsequently, molecular docking and molecular mechanics/generalized born surface area (MM-GBSA) calculations rescored these findings, while molecular dynamics (MD) simulation examined the durability of SOS2-ligand intersections.
Results: As a result, three Enamine fragments (Z284596, Z501753, and Z481369) postulated superior docking scores and binding free energies than the crystalized reference bound to SOS2 protein.
Conclusion: Furthermore, they postulated a reasonable MD profile. Overall, this study suggested three potential hit fragments with SOS2 inhibitory activity and can be experimentally verified.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244847 | PMC |
| http://dx.doi.org/10.4103/jpbs.jpbs_534_25 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ-Iodane-Mediated Cross-Nucleophile Coupling Cascade.
Org Lett
August 2025
Department of Medicinal Chemistry, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[]indolo[3,2-][2,6]naphthyridines and azepino[4,5-]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids.
View Article and Find Full Text PDFDiversity-Oriented Method Development: Multifunctional Homoallylic Amines and Azabicyclooctanes Bearing a Bridgehead Enamine.
J Am Chem Soc
August 2025
Department of Chemistry, Boston College, Merkert Chemistry Center, Chestnut Hill, Massachusetts 02467, United States.
Two methods, designed primarily for applications in diversity-oriented synthesis (DOS), are introduced. The first is a Cu-H-catalyzed multicomponent process that involves a nitrile and a trisubstituted allenyl boronate. The first set of products are homoallylic α-secondary NH-amines, containing a trisubstituted alkenyl boronate, formed with >98% enantiospecificity, in up to >98:2 dr and as a single alkene isomer (>98% ).
View Article and Find Full Text PDFA generative deep learning approach to de novo antibiotic design.
Cell
August 2025
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Eng
The antimicrobial resistance crisis necessitates structurally distinct antibiotics. While deep learning approaches can identify antibacterial compounds from existing libraries, structural novelty remains limited. Here, we developed a generative artificial intelligence framework for designing de novo antibiotics through two approaches: a fragment-based method to comprehensively screen >10 chemical fragments in silico against Neisseria gonorrhoeae or Staphylococcus aureus, subsequently expanding promising fragments, and an unconstrained de novo compound generation, each using genetic algorithms and variational autoencoders.
View Article and Find Full Text PDFA bottom-up approach to find lead compounds in expansive chemical spaces.
Commun Chem
August 2025
Unitat de Fisicoquímica, Departament de Farmàcia i Tecnologia Farmacéutica, i Fisicoquímica. Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona (UB), Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
Drug discovery starts with the identification of a "hit" compound that, following a long and expensive optimization process, evolves into a drug candidate. Bigger screening collections increase the odds of finding more and better hits. For this reason, large pharmaceutical companies have invested heavily in high-throughput screening (HTS) collections that can contain several million compounds.
View Article and Find Full Text PDFDiscovery of orally bioavailable Zika and West Nile Virus antiviral compounds targeting the NS2B-NS3 protease.
bioRxiv
June 2025
PostEra Inc, 1 Broadway, Cambridge MA 02142, USA.
Flaviviruses are a class of pathogenic viruses with pandemic potential which are typically transmitted via infected arthropods. In particular, Zika virus is sexually transmissible and causes congenital malformations if infection occurs during pregnancy. Although over 1.
View Article and Find Full Text PDF