1-(3-Chloro­phen­yl)-3-(1-p-tolyl­imidazolidin-2-yl­idene)urea

In the crystal structure of the title compound, C17H17ClN4O, the existence of only one 2-imino–oxo of the five possible N-amino–imino/O-keto–hydr­oxy tautomers is observed and the dihedral angle between the aromatic rings is 29.78 (11)°. The mol­ecular conformation is stabilized by intra­molecular C—H⋯N, N—H⋯O and C—H⋯O hydrogen bonds, in each case generating a six-membered ring. In the crystal structure, the glide-plane-related mol­ecules are linked into C(4) amide chains by inter­molecular N—H⋯O hydrogen bonds, and an inter­molecular C—H⋯O link also occurs

Influence of hormonal menopausal changes on the clinical course of psoriasis : psoriasis and menopause : part 2

Hormony płciowe znane są ze swojego wielokierunkowego wpływu na fizjologię skóry. Powszechnie kojarzy się hormony płciowe z procesem starzenia skóry, jednak przybywa także dowodów na ich wpływ na odpowiedź układu immunologicznego. Obserwacje kliniczne dotyczące wpływu cyklu miesiączkowego, ciąży czy okresu okołomenopauzalnego na przebieg wielu przewlekłych chorób zapalnych skóry sugerują wpływ hormonów na równowagę układu immunologicznego. W niniejszym doniesieniu przedstawiono najnowszą wiedzę dotyczącą epidemiologii i przebiegu łuszczycy w okresie pomenopauzalnym w kontekście zmian hormonalnych.Sex hormones are known to influence cutaneous physiology in many different ways. Although hormonal balance is probably best known for its commitment in skin ageing, there is a growing body of evidence that both estrogens and androgens may also have a significant effect on immune response. Modification of the natural course of many chronic inflammatory disorders during pregnancy, menstrual cycle or perimenopausal period suggest a hormonally induced shift in immune balance. In this paper we present and discuss current medical literature about epidemiology and course of psoriasis in the postmenopausal period with respect to hormonal changes

Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors

In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and being modulated by various factors. Some recent reports provide not only the data on ligands/modulators and resultant signals induced by them, but also deeper insights into exact pathways of signal migration and mechanisms of signal transmission through receptor structure. Combination of these computational and experimental data sheds more light on underlying mechanisms of signal transmission and signaling bias in GPCRs. In this review we focus on available clues on allosteric pathways responsible for complex signal processing within GPCRs structures, with particular emphasis on linking compatible in silico- and in vitro-derived data on the most probable allosteric connections

Overcoming Depression with 5-HT_2A Receptor Ligands

Depression is a multifactorial disorder that affects millions of people worldwide, and none of the currently available therapeutics can completely cure it. Thus, there is a need for developing novel, potent, and safer agents. Recent medicinal chemistry findings on the structure and function of the serotonin 2A (5-HT2A) receptor facilitated design and discovery of novel compounds with antidepressant action. Eligible papers highlighting the importance of 5-HT2A receptors in the pathomechanism of the disorder were identified in the content-screening performed on the popular databases (PubMed, Google Scholar). Articles were critically assessed based on their titles and abstracts. The most accurate papers were chosen to be read and presented in the manuscript. The review summarizes current knowledge on the applicability of 5-HT2A receptor signaling modulators in the treatment of depression. It provides an insight into the structural and physiological features of this receptor. Moreover, it presents an overview of recently conducted virtual screening campaigns aiming to identify novel, potent 5-HT2A receptor ligands and additional data on currently synthesized ligands acting through this protein

Interplay between Two Allosteric Sites and Their Influence on Agonist Binding in Human μ Opioid Receptor

Allostery is a widespread mechanism that allows for precise protein tuning. Its underlying mechanisms are elusive, particularly when there are multiple allosteric sites at the protein. This concerns also G-protein-coupled receptors (GPCRs), which are targets for a vast part of currently used drugs. To address this issue, we performed molecular dynamics simulations of a GPCR–human μ opioid receptor (MOR) in a native-like environment, with full agonist (R)-methadone, Na⁺ ions, and a positive modulator BMS986122 in various configurations. We found that MOR’s seventh transmembrane helix (TM VII) is central for allosteric signal transmission, and modulators affect its bending and rotation. The PAM stabilizes favorable agonist interactions, while Na⁺ tends to disrupt agonist binding. We identified two residues involved in allosteric signal transmission: Trp 7.35 at the top and Tyr 7.53 at the bottom of TM VII