Structural insights into melatonin receptors

Stauch, Benjamin; Johansson, Lars Gunnar; Cherezov, Vadim

doi:10.1111/febs.15128

Cited by 40 publications

(25 citation statements)

References 87 publications

(142 reference statements)

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“…These oncostatic functions of melatonin are known to be exerted through specific receptors [ 100 ]. Melatonin exhibits its actions by activating its two high-affinity receptors, MT1 and MT2, throughout the tissues of the body [ 101 , 102 ]. These two melatonin receptors are the most well-characterized melatonin targets, belonging to the G protein-coupled receptor (GPCR) superfamily [ 102 ].…”

Section: Aromatase-inhibitory Role Of Melatoninmentioning

confidence: 99%

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

Jin¹,

Choi²,

Heo³

et al. 2021

IJMS

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Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule’s efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer.

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Section: Aromatase-inhibitory Role Of Melatoninmentioning

confidence: 99%

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

Jin¹,

Choi²,

Heo³

et al. 2021

IJMS

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“…The difficulties in finding MT 1 ‐selective agonists can be explained, in part, by differences in the geometry of the orthosteric binding pockets in MT 1 and MT 2 crystal structures recently discussed in two commentary articles 137,138 . Despite high degree of conservation between the agonist binding pockets of MT 1 and MT 2 , the structural differences reveal why MT 2 ‐selective ligands were much more easily discovered.…”

Section: The Pharmacophores (Bicycles Figure 4)mentioning

confidence: 99%

Melatonin receptor ligands: A pharmaco‐chemical perspective

Boutin

Witt‐Enderby

Sotriffer

et al. 2020

Journal of Pineal Research

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Melatonin MT1 and MT2 receptor ligands have been vigorously explored for the last 4 decades. Inspection of approximately 80 publications in the field revealed that most melatonergic ligands were structural analogues of melatonin combining three essential features of the parent compound: an aromatic ring bearing a methoxy group and an amide side chain in a relative arrangement similar to that present in melatonin. While several series of MT2‐selective agents—agonists, antagonists, or partial agonists—were reported, the field was lacking MT1‐selective agents. Herein, we describe various approaches toward the development of melatonergic ligands, keeping in mind that most of the molecules/pharmacophores obtained were essentially melatonin copies, even though diverse tri‐ or tetra‐cyclic compounds were explored. In addition to lack of structural diversity, only few studies examined the activity of the reported melatonergic ligands in vivo. Moreover, an extensive pharmacological characterization including biopharmaceutical stability, pharmacokinetic properties, specificity toward other major receptors to name a few remained scarce. For example, many of the antagonists described were not stable in vivo, were not selective for the melatonin receptor subtype of interest, and were not fully characterized from a pharmacological standpoint. Indeed, virtual screening of large compound libraries has led to the recent discovery of potent and selective melatonin receptor agonists and partial agonists of new chemotypes. Having said this, the melatonergic field is still lacking subtype‐selective melatonin receptor antagonists “active” in vivo, which are critical to our understanding of melatonin and melatonin receptors’ role in basic physiology and disease.

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“…LCP-FRAP operates in an automated HTP mode to determine the diffusion rate of an MP in LCP. MPs with a low diffusion rate in LCP-FRAP are less likely to crystallise [14,[196][197][198].…”

Section: Membrane Protein Crystallisation and Data Collectionmentioning

confidence: 99%

Changes in Membrane Protein Structural Biology

Birch

Cheruvara

Gamage

et al. 2020

Biology

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Membrane proteins are essential components of many biochemical processes and are important pharmaceutical targets. Membrane protein structural biology provides the molecular rationale for these biochemical process as well as being a highly useful tool for drug discovery. Unfortunately, membrane protein structural biology is a difficult area of study due to low protein yields and high levels of instability especially when membrane proteins are removed from their native environments. Despite this instability, membrane protein structural biology has made great leaps over the last fifteen years. Today, the landscape is almost unrecognisable. The numbers of available atomic resolution structures have increased 10-fold though advances in crystallography and more recently by cryo-electron microscopy. These advances in structural biology were achieved through the efforts of many researchers around the world as well as initiatives such as the Membrane Protein Laboratory (MPL) at Diamond Light Source. The MPL has helped, provided access to and contributed to advances in protein production, sample preparation and data collection. Together, these advances have enabled higher resolution structures, from less material, at a greater rate, from a more diverse range of membrane protein targets. Despite this success, significant challenges remain. Here, we review the progress made and highlight current and future challenges that will be overcome.

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Structural insights into melatonin receptors

Cited by 40 publications

References 87 publications

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

Melatonin receptor ligands: A pharmaco‐chemical perspective

Changes in Membrane Protein Structural Biology

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