5-Ht

Alexander, S P H; Mathie, Alistair; Peters, John A.

doi:10.1038/sj.bjp.0706512

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…In 2003, the Human Genome Project has identified 800 receptors with a structure of seven transmembrane α-helices. [1,2] These heptahelical transmembrane regions are the structural feature of all G-protein-coupled receptors (GPCRs). [2,3] Each GPCR shows a selectivity to G-proteins that trigger an intracellular pathway after the receptor's activation.…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] These heptahelical transmembrane regions are the structural feature of all G-protein-coupled receptors (GPCRs). [2,3] Each GPCR shows a selectivity to G-proteins that trigger an intracellular pathway after the receptor's activation. [4] More than 300 of the GPCRs are non-olfactory receptors and the target for more than 50% of the drugs currently on the market that act directly or indirectly on GPCRs.…”

Section: Introductionmentioning

confidence: 99%

“…In 2003, the Human Genome Project has identified 800 receptors with a structure of seven transmembrane α‐helices …”

Section: Introductionmentioning

confidence: 99%

“…These heptahelical transmembrane regions are the structural feature of all G‐protein‐coupled receptors (GPCRs) . Each GPCR shows a selectivity to G‐proteins that trigger an intracellular pathway after the receptor's activation .…”

Section: Introductionmentioning

confidence: 99%

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Expression of proton‐sensing G‐protein‐coupled receptors in selected skin tumors

Nassios

Wallner

Haferkamp

et al. 2018

Experimental Dermatology

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Background In humans, there are four known proton‐sensing G‐Protein‐coupled receptors (pH‐GPCRs): GPR4 (GPR19), TDAG8 (GPR65, T‐cell death‐associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1) and G2A (GPR132, G2 accumulation protein). They are known to be involved in sensing changes of extracellular proton concentrations in the acidic microenvironment of tumors, which leads to altered cell proliferation, migration, metastasis, immune cell function and inflammation. However, little is known about the expression of pH‐GPCRs in the skin and especially skin cancers. Aim We studied the expression of pH‐GPCRs in selected skin cancers, that is Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Methods We did immunohistochemistry and immunofluorescence to analyse the expression of GPR4, TDAG8, OGR1 and G2A using paraffin‐embedded tissue samples (n = 4, exceptions: PDS GPR4/GPR65 n = 5, AFX GPR132 n = 3) from patients suffering from MCC, DFSP, AFX and PDS. Results (a) GPR4 was expressed on all AFX and PDS specimens. All AFX and MCC showed a positive expression of G2A. All PDS exhibited a strong positive expression of G2A. (b) MCCs neither expressed GPR4 nor TDAG8. All DFSP showed no expression of TDAG8. (c) For any other combination of GPCR and skin disease, we found positive/negative mixed results. Conclusions These are the first results on pH‐GPCRs in selected skin cancers. We provide evidence that these GPCRs are differentially expressed on the various types of skin cancers and that they can potentially be addressed as a therapeutic target in extensive disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In 2003, the Human Genome Project has identified 800 receptors with a structure of seven transmembrane α‐helices …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of proton‐sensing G‐protein‐coupled receptors in selected skin tumors

Nassios

Wallner

Haferkamp

et al. 2018

Experimental Dermatology

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7-Sulfonamido-3-benzazepines as potent and selective 5-HT2C receptor agonists: Hit-to-lead optimization

Fish

Brown

et al. 2009

Bioorganic & Medicinal Chemistry Letters

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A Case History on the Challenges of Central Nervous System and Dual Pharmacology Drug Discovery

Fish

Harrison

Wakenhut

et al. 2010

Accounts in Drug Discovery

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This chapter describes the case history of a drug discovery project targeting a centrally penetrant, dual serotonin/noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence, and highlights how key drug-like properties required for the discovery, and progression of a candidate molecule to clinical studies were successfully addressed. In particular, the medicinal chemistry strategies associated with balancing dual pharmacology with the required level of selectivity, BBB penetration, minimal CYP2D6 metabolism and pharmacokinetics are described. The use of a high confidence in vivo model and a bulk-sparing preclinical toxicology package to allow rapid determination of human pharmacokinetics were particularly important in the successful prosecution of this project.

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5-Ht

Cited by 4 publications

References 28 publications

Expression of proton‐sensing G‐protein‐coupled receptors in selected skin tumors

Expression of proton‐sensing G‐protein‐coupled receptors in selected skin tumors

7-Sulfonamido-3-benzazepines as potent and selective 5-HT2C receptor agonists: Hit-to-lead optimization

A Case History on the Challenges of Central Nervous System and Dual Pharmacology Drug Discovery

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