Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples.
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PMID:A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals. 2527 May 11

It is known that in human lung cancer samples, both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cells express the neurokinin-1 (NK-1) receptor; that after binding to the NK-1 receptor the peptide substance P (SP) elicits tumour cell proliferation and an antiapoptotic effect. By contrast, it has been demonstrated that non-peptide NK-1 receptor antagonists, after binding to the NK-1 receptor and hence by blocking the SP action in SCLC/NSCLC, exert an antiproliferative action (inhibit lung cancer cell proliferation and induce the death of tumour cells by apoptosis). It is also known that SP peptide NK-1 receptor antagonists also called SP analogue antagonists (broad-spectrum GPCR antagonists, broad-spectrum neuropeptide antagonists or synthetic analogues of SP), also exert antiproliferative actions against SCLC/NSCLC. However, the underlying mechanisms involved in this antiproliferative action remain unknown. By using competition assays with SP, here we demonstrate that the antiproliferative action exerted by the [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)] SP analogue on human H-69 SCLC and COR-L23 NSCLC cell lines, occurs at least through the NK-1 receptor.
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PMID:The antiproliferative action of [D-Arg(1), D-Phe(5), D-Trp(7,9), LEU(11)] substance P analogue antagonist against small-cell- and non-small-cell lung cancer cells could be due to the pharmacological profile of its tachykinin receptor antagonist. 2608 24

A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists. Interestingly, the acylation of the 2-amino position causes a switch from antagonist to agonist activity. The 5-phenylsulfonyl-2-amino derivative 17 showed the highest antagonist activity, while the 5-p-tolylsulfenyl-2-trifluoroacetamide derivative 20R showed the highest agonist effect. As expected, in the case of the 5-sulfinylderivatives, there was an enantiomeric discrimination in favor of one of the two enantiomers, specifically those with (SS,RC) configuration. The anticancer activity studies assessed by using human A-549 lung cancer cells and MRC-5 non-malignant lung fibroblasts, revealed a statistically significant selective cytotoxic effect of some of these 2-amino-4H-pyran derivatives toward the lung cancer cells. These studies demonstrated that the newly synthesized 4H-pyran derivatives can be used as a starting point for the synthesis of novel SP-antagonists with higher anticancer activity in the future.
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PMID:Design, synthesis and biological studies of a library of NK1-Receptor Ligands Based on a 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyran core: Switch from antagonist to agonist effect by chemical modification. 2871 Sep 64

Cough is mediated by vagal afferent fibres innervating the larynx and proximal airways. Pre-clinical studies suggest that vagal C fibres produce Substance P, one of the tachykinin family of neuropeptides, which has been shown to enhance cough via the neurokinin-1 (NK-1) receptor and studies in animal models have also shown that NK-1 antagonists are effective at blocking induced cough. In the past, tachykinin receptor antagonists have yielded disappointing results in treating asthma and cough, however most of the activity of the agents tested was restricted to the peripheral nervous system and also the outcomes measures evaluating cough not optimal. More recently a small proof of concept study has suggest that aprepitant, an NK-1 antagonist licensed for the prevention of chemotherapy induced nausea and vomiting, might have beneficial effects on cough frequency in patients with lung cancer. In this review we investigate the current evidence for the anti-tussive effect of these therapies and the clinical trials in progress.
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PMID:Emerging targets for cough therapies; NK1 receptor antagonists. 3162 73


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