Identification of novel allosteric modulators for the G-protein coupled US28 receptor of human cytomegalovirus

Kralj, Ana; Wetzel, Alexander; Mahmoudian, Shohreh; Stamminger, Thomas; Tschammer, Nuška; Heinrich, Markus R.

doi:10.1016/j.bmcl.2011.06.120

Cited by 27 publications

(37 citation statements)

References 26 publications

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“…VUF2274 and its derivatives abrogate PLCβ activation induced by US28. Di- and tetra-hydro-isoquinolines were identified as promising lead structures as allosteric inverse agonists of US28 and several derivatives have been shown to reduce US28 signaling [106]. Recently, flavonoid-based compounds were shown to inhibit US28 as inverse agonists [107].…”

Section: Hcmv Us28mentioning

confidence: 99%

Hijacking GPCRs by viral pathogens and tumor

Zhang

Feng

et al. 2016

Biochemical Pharmacology

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G protein-coupled receptors (GPCRs) constitute the largest family of molecules that transduce signal across the plasma membrane. Herpesviruses are successful pathogens that evolved diverse mechanisms to benefit their infection. Several human herpesviruses express GPCRs to exploit cellular signaling cascades during infection. These viral GPCRs demonstrate distinct biochemical and biophysical properties that result in the activation of a broad spectrum of signaling pathways. In immune-deficient individuals, human herpesvirus infection and the expression of their GPCRs are implicated in virus-associated diseases and pathologies. Emerging studies also uncover diverse mutations in components, particularly GPCRs and small G proteins, of GPCR signaling pathways that render the constitutive activation of proliferative and survival signal, which contributes to the oncogenesis of various human cancers. Hijacking GPCR-mediated signaling is a signature shared by diseases associated with constitutively active viral GPCRs and cellular mutations activating GPCR signaling, exposing key molecules that can be targeted for anti-viral and anti-tumor therapy.

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Section: Hcmv Us28mentioning

confidence: 99%

Hijacking GPCRs by viral pathogens and tumor

Zhang

Feng

et al. 2016

Biochemical Pharmacology

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“…If oxygen-containing nitric oxide, as present in streams of waste gas, could be used to form oximes in Meerwein arylations, this might provide a new technique for recycling nitric oxide. Closer investigations showed that a nitric oxide content of at least 10 vol% in air 61 was necessary to obtain desired oximes, such as 41, in reasonable yields (Scheme 13) from diazonium salt 42 and methyl acrylate (39). 62 During this follow-up study on the new type of Meerwein arylation, we also showed that a …”

Section: Carbonitrosation Reactionsmentioning

confidence: 93%

How the Structural Elucidation of the Natural Product Stephanosporin Led to New Developments in Aryl Radical and Medicinal Chemistry

Fehler

Heinrich

2015

Synlett

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The intent of this account is to provide a focused overview of recent developments in aryl radical chemistry, especially extensions and applications of the Meerwein arylation and the Gomberg-Bachmann reaction. Although most of the reactions and methods described were discovered on the basis of earlier findings made by our group or logically depend on newly discovered reactivities or mechanistic principles, the rapid evolution of radical chemistry can nevertheless be traced back to the behavior of the natural product stephanosporin, which is capable of liberating 2-chloro-4-nitrophenol via an aryl radical intermediate.

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“…The "molecular switches," which are responsible for the switching between positive and negative efficacy of allosteric modulators, are so far unpredictable as the path from an agonist to an inverse agonist could be as short as a methyl group [56,126] (Fig. 11).…”

Section: "Molecular Switches"mentioning

confidence: 99%

Allosteric Modulation of Chemokine Receptors

Tschammer

Christopoulos

Kenakin

2014

Topics in Medicinal Chemistry

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A central role of chemokines and their receptors in inflammatory processes has spurred numerous screening campaigns dedicated to the search for chemokine-receptor antagonists, which largely failed to deliver drugs for the treatment of inflammatory diseases. The quest for effective chemokine-receptor drug candidates thus continues, and the concept of allosteric targeting of the receptors may be the way forward. In this review, the complex allosteric mechanisms by which the functions of chemokines and their receptors are fine-tuned will be discussed and their impact on preclinical drug discovery presented. The opportunities and challenges of bench-to-clinic approaches are elucidated. We propose that while allosteric modulation of chemokine receptors adds a level of complexity to analyses and approaches to drug discovery, it also introduces a tremendous capacity for pharmacologic control of this physiological system for therapeutic advantage.

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Identification of novel allosteric modulators for the G-protein coupled US28 receptor of human cytomegalovirus

Cited by 27 publications

References 26 publications

Hijacking GPCRs by viral pathogens and tumor

Hijacking GPCRs by viral pathogens and tumor

How the Structural Elucidation of the Natural Product Stephanosporin Led to New Developments in Aryl Radical and Medicinal Chemistry

Allosteric Modulation of Chemokine Receptors

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