Category: 321673-30-7

Wang, Lei published the artcileStructures of the Human PGD₂ Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition, Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Molecular Cell (2018), 72(1), 48-59.e4, database is CAplus and MEDLINE.

The signaling of prostaglandin D₂ (PGD₂) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clin. investigation, and one compound, fevipiprant, has advanced to phase 3 clin. trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chem. diverse CRTH2 antagonists. Structural anal. suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD₂, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.

Molecular Cell published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C25H47NO8, Safety of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Saeki, Kazuko published the artcileIdentification, signaling, and functions of LTB₄ receptors, Formula: C12H23N3S, the publication is Seminars in Immunology (2017), 30-36, database is CAplus and MEDLINE.

Leukotriene B₄ (LTB₄), a lipid mediator produced from arachidonic acid, is a chemoattractant for inflammatory leukocytes. We identified two receptors for LTB₄, the high-affinity receptor BLT1 and the low-affinity receptor BLT2. BLT1 is expressed in various subsets of leukocytes, and analyses of BLT1-deficient mice revealed that the LTB₄/BLT1 axis enhances leukocyte recruitment to infected sites, and is involved in the elimination of pathogens. Hyperactivation of the LTB₄/BLT1 axis induces acute and chronic inflammation, resulting in various inflammatory diseases. BLT2 was originally identified as a low-affinity receptor for LTB₄, and we later identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity ligand for BLT2. BLT2 is highly expressed in epithelial cells in various tissues including intestine and skin. Large quantities of 12-HHT are produced by activated platelets during skin injury, and activation of BLT2 on epidermal keratinocytes accelerates skin wound healing by enhancing cell migration. BLT2 signaling also enhances cell-cell junctions, protectes against transepidermal water loss, and preventes entry of environmental substances into the body.

Seminars in Immunology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Formula: C12H23N3S.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Oi, Naomi published the artcileLTA4H regulates cell cycle and skin carcinogenesis, Quality Control of 321673-30-7, the publication is Carcinogenesis (2017), 38(7), 728-737, database is CAplus and MEDLINE.

Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by neg. regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model. LTA4H depletion dramatically decreased anchorage-dependent and -independent skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase. Moreover, our findings showed that depletion of LTA4H enhanced p27 protein stability, which was associated with decreased phosphorylation of CDK2 at Thr160 and inhibition of the CDK2/cyclin E complex, resulting in down-regulated p27 ubiquitination. These findings indicate that LTA4H is critical for skin carcinogenesis and is an important mediator of cell cycle and the data begin to clarify the mechanisms of LTA4H’s role in cancer development.

Carcinogenesis published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Quality Control of 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Li, Dan published the artcileSLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors, HPLC of Formula: 321673-30-7, the publication is Science Immunology (2022), 7(67), eabj5501, database is CAplus and MEDLINE.

The interaction of SIRPα with CD47 represents a major mechanism for preventing macrophage phagocytosis. However, CD47-independent mechanisms are poorly defined. Here, we report a critical role of SLAM family receptors (SFRs), ubiquitously expressed on hematopoietic cells and forming homotypic interactions, in constraining macrophage phagocytosis. We found that SFR deficiency triggered macrophage phagocytosis of hematopoietic cells, leading to severe rejection of donor hematopoietic graft in recipient mice. Specific SFR members, mainly SLAMF3 and SLAMF4, were identified as “don’t eat me” receptors on macrophages. These receptors inhibited “eat me” signals, such as LRP1-mediated activation of mTOR and Syk, through SH2 domain-containing phosphatases. SFRs combined with, but were independent of, CD47 to mitigate macrophage phagocytosis, and the combined deletion of SFRs and CD47 resulted in hematopoietic cytopenia in mice. This SFR-mediated tolerance was compromised in patients with hemophagocytic lymphohistiocytosis, a syndrome characterized by inappropriate phagocytosis toward hematopoietic cells. Loss of SFRs potently elicited macrophage rejection of hematopoietic tumors. Deletion of SFRs also significantly enhanced the phagocytosis of CD19-pos. hematopoietic targets by the macrophages expressing the chimeric CD19 antigen receptor. Therefore, SFR-mediated inhibition of macrophage phagocytosis is critical to hematopoietic homeostasis, and SFRs may represent previously unknown targets for tumor immunotherapy.

Science Immunology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, HPLC of Formula: 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Xu, Shisan published the artcileProlonged neutrophil retention in the wound impairs zebrafish heart regeneration after cryoinjury., Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Fish & Shellfish Immunology (2019), 447-454, database is CAplus and MEDLINE.

Neutrophils are the first line defenders in the innate immune response, and rapidly migrate to an infected or injured area. Recently, bidirectional migration of neutrophils to the wound and the corresponding functions have become popular research pursuits. In zebrafish larvae, CXCR1/CXCL8 is the predominant chemoattractant pathway to recruit neutrophil to wound, while CXCR2/CXCL8 pathway mediate neutrophil dispersal in wound after injury. Here, we found that both CXCR1/CXCL8 and LTB4/BLT1 signals are activated in zebrafish heart after cryoinjury. And with a CXCR1/2 selective inhibitor (SB225002) treatment, the recruitment of neutrophils was not affected, but reverse migration of neutrophils was inhibited after cryoinjury of heart. We suggested that the neutrophil recruitment to cryoinjured area might be mediated by LTB4/BLT1 signals at the presence of SB225002. Therefore, SB225002 treatment resulted more accumulation and long retention of neutrophils in the injured heart. The long retention of neutrophils in the wound promoted revascularization in the injured heart; however, the AKT/mTOR pathway was inhibited and the regeneration was impaired. Our findings suggest that retention of neutrophils is a well-orchestrated process and might regulate regeneration by the AKT/mTOR pathway.

Fish & Shellfish Immunology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C15H10O2, Safety of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Maddaloni, Ernesto published the artcileHigh density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes, HPLC of Formula: 321673-30-7, the publication is Cardiovascular Diabetology (2017), 116/1-116/11, database is CAplus and MEDLINE.

Background: Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN + monocytes in a unique population with ≥50 years of T1D, the 50-Yr Joslin Medalists (J50M). Methods: CD45 bright/CD14 + /OCN + cells in the circulating mononuclear blood cell fraction were quantified by flow cytometry and reported as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN expression in human monocytes in vitro. Results: Subjects without history of CVD (n = 16) showed lower levels of OCN + monocytes than subjects with CVD (n = 14) (13.1 α 8.4% vs 19.9 α 6.4%, p = 0.02). OCN + monocytes level was inversely related to total high d. lipoprotein (HDL) cholesterol levels (r = -0.424, p = 0.02), large (r = -0.413, p = 0.02) and intermediate (r = -0.445, p = 0.01) HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL significantly increased the number of OCN + monocytes (p < 0.01). This action of OxLDL was significantly reduced by the addition of HDL in a concentration dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced the effects of both OxLDL and HDL (p < 0.05). Conclusions: Low OCN + monocytes levels are associated with lack of CVD in people with long duration T1D. A possible mechanism for the increased OCN + monocytes could be the elevated levels of oxidized lipids due to diabetes which may be inhibited by HDL. These findings suggest that circulating OCN + monocytes could be a marker for vascular disease in diabetic patients and possibly modified by HDL elevation.

Cardiovascular Diabetology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, HPLC of Formula: 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wei, Congwen published the artcileHDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry, Application of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Nature Metabolism (2020), 2(12), 1391-1400, database is CAplus and MEDLINE.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-d. lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacol. SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible mol. connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

Nature Metabolism published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H14IN, Application of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Nakanishi, Yoshimitsu published the artcileStepwise phosphorylation of leukotriene B₄ receptor 1 defines cellular responses to leukotriene B₄, Formula: C12H23N3S, the publication is Science Signaling (2018), 11(544), eaao5390/1-eaao5390/15, database is CAplus and MEDLINE.

Leukotriene B₄ (LTB₄) receptor type 1 (BLT1) is abundant in phagocytic and immune cells and plays crucial roles in various inflammatory diseases. BLT1 is phosphorylated at several serine and threonine residues upon stimulation with the inflammatory lipid LTB₄. Using Phos-tag gel electrophoresis to sep. differentially phosphorylated forms of BLT1, we identified two distinct types of phosphorylation, basal and ligand-induced, in the carboxyl terminus of human BLT1. In the absence of LTB₄, the basal phosphorylation sites were modified to various degrees, giving rise to many different phosphorylated forms of BLT1. Different concentrations of LTB₄ induced distinct phosphorylation events, and these ligand-induced modifications facilitated addnl. phosphorylation events at the basal phosphorylation sites. Because neutrophils migrate toward inflammatory sites along a gradient of LTB₄, the degree of BLT1 phosphorylation likely increases in parallel with the increase in LTB₄ concentration as the cells migrate. At high concentrations of LTB₄, deficiencies in these two types of phosphorylation events impaired chemotaxis and β-hexosaminidase release, a proxy for degranulation, in Chinese hamster ovary (CHO-K1) and rat basophilic leukemia (RBL-2H3) cells, resp. These results suggest that an LTB₄ gradient around inflammatory sites enhances BLT1 phosphorylation in a stepwise manner to facilitate the precise migration of phagocytic and immune cells and the initiation of local responses, including degranulation.

Science Signaling published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Formula: C12H23N3S.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Khairullina, V. R. published the artcileStructural Analysis of Leukotriene B4 (LBT₄) Receptor (BLT₁ AND BLT₂) Antagonists, Application of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Pharmaceutical Chemistry Journal (2014), 48(5), 317-322, database is CAplus.

The structural characteristics typical of highly and moderately effective antagonists of BLT₁ and BLT₂ receptors were identified and the extents of their influences on the target property were evaluated. Two models for predicting inhibitory activity were constructed for series of sulfur-, nitrogen- and oxygen-containing heterocyclic compounds with significant prognostic levels of greater than 80% using two methods based on sample recognition theory. These structural patterns can be used for virtual screening of potential drugs for antiallergic activity associated with blockade of leukotriene LTB₄-sensitive BLT₁ and BLT₂ receptors.

Pharmaceutical Chemistry Journal published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Application of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Sato, Yuki published the artcileInvolvement of cholesterol membrane transporter Niemann-Pick C1-like 1 in the intestinal absorption of lutein, Quality Control of 321673-30-7, the publication is Journal of Pharmacy & Pharmaceutical Sciences (2012), 15(2), 256-264, database is CAplus and MEDLINE.

Purpose: Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. The physiol. importance of an orally administered compound depends on its interaction with target tissues. It is therefore important to clarify the absorption mechanism in the intestine. Cholesterol membrane transporters Niemann-Pick C1 Like 1 (NPC1L1) and scavenger receptor class B type 1 (SR-B1) are involved in the intestinal absorption of highly lipophilic compounds including cholesterol. Ezetimibe, a selective inhibitor of intestinal NPC1L1, is the widespread lipid-lowering agent. It is important to investigate the possibility of food-drug interactions in order to prevent undesirable and harmful clin. consequences. The aim of this work was to determine whether NPC1L1, SR-B1 and other transporters are involved in absorption of lutein. Methods: Caco-2 cells were used for accumulation and permeability study of lutein. Lutein concentration was determined by an HPLC system. The cDNA of transporters was isolated from total RNA of Caco-2 cells and the expression of these transporters was confirmed by RT-PCR (reverse transcription – polymerase chain reaction). Results: Ezetimibe inhibited up to 40% of lutein accumulation by Caco-2 cell monolayers. Block lipid transport 1 (BLT-1), a selective chem. inhibitor of SR-B1, also inhibited lutein accumulation by Caco-2 cells. On the other hand, ATP-depletion reagents (sodium fluoride and sodium azide or carbonyl cyanide m-chlorophenylhydrazone) did not influence the accumulation or permeation of lutein significantly. Conclusions: The results show that lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters.

Journal of Pharmacy & Pharmaceutical Sciences published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Quality Control of 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics