Results 111 to 120 of about 13,221 (154)

A negative allosteric modulator modulates GABAB-receptor signalling through GB2 subunits

Biochemical Journal, 2016
An γ-aminobutyric acid type B (GABAB)-receptor mediates slow and prolonged synaptic inhibition in the central nervous system, which represents an interesting target for the treatment of various diseases and disorders of the central nervous system.
Bing, Sun, Linhai, Chen, Lei, Liu, Zhixiong, Xia, Jean-Philippe, Pin, Fajun, Nan, Jianfeng, Liu   +6 more
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Extracellular binding sites of positive and negative allosteric P2X4 receptor modulators

Life Sciences, 2022
P2X receptors are ATP-gated ion channels which play a role in many pathophysiological conditions. They are considered as novel drug targets, particularly in the fields of pain, (neuro) inflammation, and cancer. Due to difficulties in developing drug-like orthosteric ligands that bind to the highly polar ATP binding site, the design of positive and ...
Stephanie Weinhausen, Jessica Nagel, Vigneshwaran Namasivayam, Claudia Spanier, Aliaa Abdelrahman, Theodor Hanck, Ralf Hausmann, Christa E. Müller   +7 more
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Negative allosteric modulation of the µ-opioid receptor

2023
AbstractThe µ-opioid receptor (µOR) is a well-established target for analgesia, yet conventional opioid receptor agonists cause serious adverse effects, notably addiction and respiratory depression, which have led to the present opioid overdose epidemic. µOR negative allosteric modulators (NAMs) may serve as powerful tools in preventing opioid overdose
Evan S. O’Brien, Vipin Ashok Rangari, Amal El Daibani, Shainnel O. Eans, Betsy White, Haoqing Wang, Yuki Shiimura, Kaavya Krishna Kumar, Kevin Appourchaux, Weijiao Huang, Chensong Zhang, Jesper M. Mathiesen, Tao Che, Jay P. McLaughlin, Susruta Majumdar, Brian K. Kobilka   +15 more
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PKCε acts as negative allosteric modulator of EGF receptor signalling

Cellular Signalling, 2011
Protein kinase C ε (PKCε) is a transforming oncogene and plays a pivotal role in numerous cellular processes including proliferation, invasion and differentiation. Recently, we described a function of PKCε as a scaffold protein linking PLCγ1 to the EGFR module.
Simona, Weisheit, Claudia, Schäfer, Carmen, Mertens, Alexander, Berndt, Claus, Liebmann   +4 more
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6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2011
A series of 6-aryl-3-pyrrolidinylpyridine analogs was explored as structurally novel negative allosteric modulators of the mGlu5 receptor lacking an alkyne or oxadiazole moiety. Compounds in this series were characterized by tractable SAR, good in vitro potencies and brain penetration in rodents.
Jesse M, Weiss, Hermogenes N, Jimenez, Guiying, Li, Myriam, April, Michelle A, Uberti, Maria D, Bacolod, Robb M, Brodbeck, Darío, Doller   +7 more
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Calcium-Sensing Receptor Negative Allosteric Modulators Oppose Contraction of Mouse Airways

American Journal of Respiratory Cell and Molecular Biology, 2023
Asthma is a heterogeneous chronic airway disease with an unmet need for improved therapeutics in uncontrolled severe disease. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor upregulated in asthma. The CaSR agonist, spermine, is also increased in asthmatic airways and contributes to bronchoconstriction.
Jiayin Diao, Maggie Lam, Karen J. Gregory, Katie Leach, Jane E. Bourke   +4 more
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Structure-Based Virtual Screening to Identify Negative Allosteric Modulators of NMDA

Medicinal Chemistry, 2022
Background:NMDA (N-methyl-D-aspartate) receptor is one of the ionotropic receptor subtypes of glutamate, the most abundant excitatory neurotransmitter in the human brain. Besides physiological roles in learning and memory, neuronal plasticity and somatosensory function NMDAR overstimulation are also implicated in a pathophysiological mechanism of ...
Zaid Anis, Sherwani, Ruqaiya, Khalil, Mohammad, Nur-E-Alam, Sarfaraz, Ahmed, Zaheer, Ul-Haq   +4 more
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In search of negative allosteric modulators of biological targets

Drug Discovery Today, 2009
The value of using negative allosteric modulators of protein function in therapeutic treatment of human diseases is becoming more apparent. Many current screening paradigms, however, are not consciously designed to discover negative allosteric modulators, and those that are serendipitously discovered can be easily overlooked during the hit-picking ...
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The discovery of novel calcium sensing receptor negative allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2009
The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.
Gayatri, Balan, Jonathan, Bauman, Samit, Bhattacharya, Mayda, Castrodad, David R, Healy, Michael, Herr, Paul, Humphries, Sandra, Jennings, Amit S, Kalgutkar, Brendon, Kapinos, Vishal, Khot, Kimberly, Lazarra, Mei, Li, Yan, Li, Constantin, Neagu, Robert, Oliver, David W, Piotrowski, David, Price, Hong, Qi, Holly A, Simmons, James, Southers, Liuqing, Wei, Yan, Zhang, Vishwas M, Paralkar   +23 more
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QSAR Study of Anticonvulsant Negative Allosteric Modulators of the AMPA Receptor

Journal of Medicinal Chemistry, 2004
A quantitative structure-activity relationship (QSAR) study was performed on a set of 49 negative allosteric modulators of AMPA receptor, acting as anticonvulsant agents, using multiple linear regression. The predictive ability of the resulting model was evaluated against a set of 12 compounds; the results showed good statistics in regression and ...
MACCHIARULO, Antonio, De Luca L., Costantino G., BARRECA, MARIA LETIZIA, Gitto R., PELLICCIARI, Roberto, Chimirri A.   +6 more
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