We identified small molecule NTS1R agonist compounds through virtual screening of the corporate database using a ROCS approach that searches multi-conformer representations efficiently. As a starting point for the ROCS search, we used the known NTS1R selective antagonist, SR-48527, based on the hypothesis that NT agonists and antagonists might share similar binding regions. Conformations were expanded and selected as database search queries based on a cluster analysis. The search provided us with virtual hits that were tested in intracellular calcium mobilization assays of NTS1R agonist and antagonist activities measured in FLIPR format as well as in [(3)H]NT competition binding studies. The results indicated that two initial hits produced partial agonist activity with potency in the moderate micromolar range.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2008.09.075DOI Listing

Publication Analysis

Top Keywords

virtual screening
8
nts1r agonist
8
identification neurotensin
4
neurotensin nts1
4
nts1 receptor
4
receptor partial
4
partial agonists
4
agonists ligand-based
4
ligand-based virtual
4
screening approach
4

Similar Publications

There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment.

View Article and Find Full Text PDF

Objectives: To investigate the image quality and diagnostic performance with ultra-low dose dual-layer detector spectral CT (DLSCT) by various reconstruction techniques for evaluation of pulmonary nodules.

Materials And Methods: Between April 2023 and December 2023, patients with suspected pulmonary nodules were prospectively enrolled and underwent regular-dose chest CT (RDCT; 120 kVp/automatic tube current) and ultra-low dose CT (ULDCT; 100 kVp/10 mAs) on a DLSCT scanner. ULDCT was reconstructed with hybrid iterative reconstruction (HIR), electron density map (EDM), and virtual monoenergetic images at 40 keV and 70 keV.

View Article and Find Full Text PDF

Management of mass casualty incidents: a systematic review and clinical practice guideline update.

Eur J Trauma Emerg Surg

January 2025

Institute for Research in Operative Medicine (IFOM), Faculty of Health, School of Medicine, Witten/Herdecke University, Ostmerheimer Str. 200, 51109, Cologne, Germany.

Purpose: Our aim was to generate evidence- and consensus-based recommendations for the management of mass casualty incidents (MCIs) based on current evidence. This guideline topic is part of the 2022 update of the German guideline on the treatment of patients with severe/multiple injuries.

Methods: MEDLINE and Embase were systematically searched to August 2021.

View Article and Find Full Text PDF

Robotic-assisted thoracic surgery has become increasingly utilized in recent years. Complex lung cancer resection surgery can be performed using a robotic approach. It facilitates 3-dimentional visualization of structures, enhanced manipulation of tissues and precise movements.

View Article and Find Full Text PDF

Introduction: Upper limb (UL) impairment is common in people with multiple sclerosis (pwMS), and functional recovery of the UL is a key rehabilitation goal. Technology-based approaches, like virtual reality (VR), are increasingly promising. While most VR environments are task-oriented, our clinical approach integrates neuroproprioceptive 'facilitation and inhibition' (NFI) principles.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!