Tag: M.W=300-400

Niculescu, A. B.; Le-Niculescu, H.; Roseberry, K.; Wang, S.; Hart, J.; Kaur, A.; Robertson, H.; Jones, T.; Strasburger, A.; Williams, A.; Kurian, S. M.; Lamb, B.; Shekhar, A.; Lahiri, D. K.; Saykin, A. J. published the artcile< Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs>, COA of Formula: C22H21N3O2, the main research area is Alzheimer disease blood biomarker memory pharmacogenomics.

We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Addnl. top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto pos. controls for our whole-genome gene expression discovery approach. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a mol. basis for clin. co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin).

Molecular Psychiatry published new progress about Alzheimer disease. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, COA of Formula: C22H21N3O2.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Antczak, Christophe; Wee, Boyoung; Radu, Constantin; Bhinder, Bhavneet; Holland, Eric C.; Djaballah, Hakim published the artcile< A High-Content Assay Strategy for the Identification and Profiling of ABCG2 Modulators in Live Cells>, Name: YM-90709, the main research area is ABCG2 protein ABC transporter glioblastoma.

ABCG2 is a member of the ATP-binding cassette (ABC) family of transporters, the overexpression of which has been implicated in resistance to various chemotherapeutic agents. Though a number of cell-based assays to screen for inhibitors have been reported, they do not provide a content-rich platform to discriminate toxic and autofluorescent compounds To fill this gap, we developed a live high-content cell-based assay to identify inhibitors of ABCG2-mediated transport and, at the same time, assess their cytotoxic effect and potential optical interference. We used a pair of isogenic U87MG human glioblastoma cell lines, with one stably overexpressing the ABCG2 transporter. JC-1 (J-aggregate-forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol carbocyanine iodide) was selected as the optimal reporter substrate for ABCG2 activity, and the resulting assay was characterized by a Z’ value of 0.50 and a signal-to-noise (S/N) ratio of 14 in a pilot screen of ∼7,000 diverse chems. The screen led to the identification of 64 unique nontoxic positives, yielding an initial hit rate of 1%, with 58 of them being confirmed activity. In addition, treatment with two selected confirmed positives suppressed the side population of U87MG-ABCG2 cells that was able to efflux the Hoechst dye as measured by flow cytometry, confirming that they constitute potent new ABCG2 transporter inhibitors. Our results demonstrate that our live cell and content-rich platform enables the rapid identification and profiling of ABCG2 modulators, and this new strategy opens the door to the discovery of compounds targeting the expression and/or trafficking of ABC transporters as an alternative to functional inhibitors that failed in the clinic.

Assay and Drug Development Technologies published new progress about Antioxidants. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Name: YM-90709.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Jo, Hakryul; Patterson, Victoria; Stoessel, Sean; Kuan, Chia-Yi; Hoh, Josephine published the artcile< Protoporphyrins enhance oligomerization and enzymatic activity of HtrA1 serine protease>, Related Products of 163769-88-8, the main research area is protoporphyrin oligomerization HtrA1 serine protease protoporphyria hemin.

High temperature requirement protein A1 (HtrA1), a secreted serine protease of the HtrA family, is associated with a multitude of human diseases. However, the exact functions of HtrA1 in these diseases remain poorly understood. We seek to unravel the mechanisms of HtrA1 by elucidating its interactions with chem. or biol. modulators. To this end, we screened a small mol. library of 500 bioactive compounds to identify those that alter the formation of extracellular HtrA1 complexes in the cell culture medium. An initial characterization of two novel hits from this screen showed that protoporphyrin IX (PPP-IX), a precursor in the heme biosynthetic pathway, and its metalloporphyrin (MPP) derivatives fostered the oligomerization of HtrA1 by binding to the protease domain. As a result of the interaction with MPPs, the proteolytic activity of HtrA1 against Fibulin-5, a specific HtrA1 substrate in age-related macular degeneration (AMD), was increased. This phys. interaction could be abolished by the missense mutations of HtrA1 found in patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Furthermore, knockdown of HtrA1 attenuated apoptosis induced by PPP-IX. These results suggest that PPP-IX, or its derivatives, and HtrA1 may function as co-factors whereby porphyrins enhance oligomerization and the protease activity of HtrA1, while active HtrA1 elevates the pro-apoptotic actions of porphyrin derivatives Further anal. of this interplay may shed insights into the pathogenesis of diseases such as AMD, CARASIL and protoporphyria, as well as effective therapeutic development.

PLoS One published new progress about Age-related macular degeneration. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Related Products of 163769-88-8.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Morokata, Tatsuaki; Suzuki, Keiko; Ida, Kenji; Yamada, Toshimitsu published the artcile< Effect of a novel interleukin-5 receptor antagonist, YM-90709, on antigen-induced eosinophil infiltration into the airway of BDF1 mice>, Recommanded Product: YM-90709, the main research area is YM90709 antiinflammatory IL5 receptor antagonist eosinophil inflammation respiratory tract.

A newly synthesized compound, YM-90709, 2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline, was previously reported to specifically inhibit the binding of interleukin-5 (IL-5) to its receptor (R) on human eosinophils. In this study, the i.v. injection of YM-90709 inhibited antigen-induced infiltration of eosinophils into the bronchoalveolar lavage fluid (BALF) of BDF1 mice, with an ED50 value of 0.050 mg/kg. Anti-murine IL-5 monoclonal antibody (mAb) also inhibited the infiltration of eosinophils with an ED50 value of 0.035 mg/kg. These results indicate that YM-90709, which is a novel IL-5R antagonist, inhibits antigen-induced eosinophil recruitment into the airway, the same as anti-IL-5 mAb does.

Immunology Letters published new progress about Allergic inflammation. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Recommanded Product: YM-90709.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Reinhart, Peter H.; Kaltenbach, Linda S.; Essrich, Christian; Dunn, Denise E.; Eudailey, Joshua A.; DeMarco, C. Todd; Turmel, Gregory J.; Whaley, Jennifer C.; Wood, Andrew; Cho, Seongeun; Lo, Donald C. published the artcile< Identification of anti-inflammatory targets for Huntington's disease using a brain slice-based screening assay>, Synthetic Route of 163769-88-8, the main research area is Huntington disease antiinflammatory target brain slice screening assay.

Huntington’s disease (HD) is a late-onset, neurodegenerative disease for which there are currently no cures nor disease-modifying treatments. Here we report the identification of several potential anti-inflammatory targets for HD using an ex vivo model of HD that involves the acute transfection of human mutant huntington-based constructs into rat brain slices. This model recapitulates key components of the human disease, including the formation of intracellular huntington protein (HTT)-containing inclusions and the progressive neurodegeneration of striatal neurons-both occurring within the native tissue context of these neurons. Using this “”high-throughput biol.”” screening platform, we conducted a hypothesis-neutral screen of a collection of drug-like compounds which identified several anti-inflammatory targets that provided neuroprotection against HTT fragment-induced neurodegeneration. The nature of these targets provide further support for non-cell autonomous mechanisms mediating significant aspects of neuropathogenesis induced by mutant HTT fragment proteins.

Neurobiology of Disease published new progress about Adenosine A2A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Synthetic Route of 163769-88-8.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Gut, Philipp; Stainier, Didier Y. R. published the artcile< Whole-Organism Screening for Modulators of Fasting Metabolism Using Transgenic Zebrafish>, COA of Formula: C22H21N3O2, the main research area is small mol high throughput screening fasting metabolism zebrafish review.

A review. Organismal energy homeostasis is maintained by complex interorgan communications making the discovery of novel drugs against metabolic diseases challenging using traditional high-throughput approaches in vitro. Here, we describe a method that rapidly identifies small mols. with an impact on organismal energy balance in vivo. Specifically, we developed a whole-organism screen for modulators of fasting metabolism using transgenic bioluminescence-reporter zebrafish for the gluconeogenic gene phosphoenolpyruvate-carboxykinase 1 (pck1).

Methods in Molecular Biology (New York, NY, United States) published new progress about Bioluminescence. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, COA of Formula: C22H21N3O2.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Morokata, Tatsuaki; Suzuki, Keiko; Ida, Kenji; Tsuchiyama, Hirotaka; Ishikawa, Jun; Yamada, Toshimitsu published the artcile< Effect of a novel interleukin-5 receptor antagonist, YM-90709 (2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline), on antigen-induced airway inflammation in BN rats>, Category: quinoxaline, the main research area is interleukin receptor antagonist YM90709 dimethoxydimethyldihydrobenzoindolizinoquinoxaline antigen airway inflammation.

Interleukin-5 (IL-5) plays an important role in the activation of eosinophils in the allergic inflammation in conditions such as asthma, rhinitis, and atopic dermatitis. A newly synthesized compound, YM-90709 (2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline), was previously reported to inhibit the binding of IL-5 to its receptor (R) on human eosinophils and eosinophilic HL-60 clone 15 cells. However, it did not inhibit the binding of granulocyte-macrophage colony-stimulating factor (GM-CSF) to its receptor on the same cells. In this study, the i.v. injection of YM-90709 resulted in the inhibition of antigen-induced infiltration of eosinophils and lymphocytes, but not neutrophils or monocytes, into the bronchoalveolar lavage fluid (BALF) of Brown-Norway (BN) rats, with ED50 values of 0.32 mg/kg and 0.12 mg/kg, resp. Two glucocorticoids, dexamethasone and prednisolone, inhibited neutrophil, eosinophil, and lymphocyte infiltration into the BALF. However, both significantly reduced the number of peripheral blood leukocytes and bone marrow leukocytes. In contrast, YM-90709 did not affect the peripheral blood leukocytes or the bone marrow leukocytes. These results indicate that, in this model, YM-90709, which is a novel IL-5 R antagonist, inhibits antigen-induced eosinophil and lymphocyte recruitment into the airway, without any suppressive effects on peripheral blood leukocytes or bone marrow leukocytes, in contrast to the glucocorticoids.

International Immunopharmacology published new progress about Antigens Role: ADV (Adverse Effect, Including Toxicity), BIOL (Biological Study). 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Category: quinoxaline.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Morokata, Tatsuaki; Ida, Kenji; Yamada, Toshimitsu published the artcile< Characterization of YM-90709 as a novel antagonist which inhibits the binding of interleukin-5 to interleukin-5 receptor>, Recommanded Product: YM-90709, the main research area is YM90709 IL5 receptor eosinophil.

Interleukin-5 (IL-5) plays an important role in the activation of eosinophils in allergic inflammation including asthma and atopic dermatitis. A newly synthesized compound, YM-90709, 2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline, is reported here to inhibit the binding of IL-5 to its receptor on peripheral human eosinophils and butyric acid-treated eosinophilic HL-60 clone 15 cells, with IC50 values of 1.0 and 0.57 μM, resp. In contrast, YM-90709 did not affect the binding of granulocyte-macrophage colony-stimulating factor (GM-CSF) to its receptor on eosinophils and eosinophilic HL-60 clone 15 cells. In functional assays, YM-90709 inhibited IL-5-prolonged eosinophil survival with an IC50 value of 0.45 μM and did not affect the GM-CSF-prolonged eosinophil survival. Furthermore, YM-90709 inhibited the IL-5-induced but not GM-CSF-induced tyrosine phosphorylation of Janus kinase 2 (JAK2) in eosinophilic HL-60 clone 15 cells. These results indicate that YM-90709 is a novel IL-5 inhibitor which selectively blocks the binding of IL-5 to the IL-5 receptor (IL-5R).

International Immunopharmacology published new progress about Eosinophil. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Recommanded Product: YM-90709.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Gut, Philipp; Stainier, Didier Y. R. published the artcile< Whole-Organism Screening for Modulators of Fasting Metabolism Using Transgenic Zebrafish>, Reference of 163769-88-8, the main research area is small mol high throughput screening fasting metabolism zebrafish review.

A review. Organismal energy homeostasis is maintained by complex interorgan communications making the discovery of novel drugs against metabolic diseases challenging using traditional high-throughput approaches in vitro. Here, we describe a method that rapidly identifies small mols. with an impact on organismal energy balance in vivo. Specifically, we developed a whole-organism screen for modulators of fasting metabolism using transgenic bioluminescence-reporter zebrafish for the gluconeogenic gene phosphoenolpyruvate-carboxykinase 1 (pck1).

Methods in Molecular Biology (New York, NY, United States) published new progress about Bioluminescence. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Reference of 163769-88-8.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Morokata, Tatsuaki; Suzuki, Keiko; Ida, Kenji; Tsuchiyama, Hirotaka; Ishikawa, Jun; Yamada, Toshimitsu published the artcile< Effect of a novel interleukin-5 receptor antagonist, YM-90709 (2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline), on antigen-induced airway inflammation in BN rats>, Recommanded Product: YM-90709, the main research area is interleukin receptor antagonist YM90709 dimethoxydimethyldihydrobenzoindolizinoquinoxaline antigen airway inflammation.

Interleukin-5 (IL-5) plays an important role in the activation of eosinophils in the allergic inflammation in conditions such as asthma, rhinitis, and atopic dermatitis. A newly synthesized compound, YM-90709 (2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline), was previously reported to inhibit the binding of IL-5 to its receptor (R) on human eosinophils and eosinophilic HL-60 clone 15 cells. However, it did not inhibit the binding of granulocyte-macrophage colony-stimulating factor (GM-CSF) to its receptor on the same cells. In this study, the i.v. injection of YM-90709 resulted in the inhibition of antigen-induced infiltration of eosinophils and lymphocytes, but not neutrophils or monocytes, into the bronchoalveolar lavage fluid (BALF) of Brown-Norway (BN) rats, with ED50 values of 0.32 mg/kg and 0.12 mg/kg, resp. Two glucocorticoids, dexamethasone and prednisolone, inhibited neutrophil, eosinophil, and lymphocyte infiltration into the BALF. However, both significantly reduced the number of peripheral blood leukocytes and bone marrow leukocytes. In contrast, YM-90709 did not affect the peripheral blood leukocytes or the bone marrow leukocytes. These results indicate that, in this model, YM-90709, which is a novel IL-5 R antagonist, inhibits antigen-induced eosinophil and lymphocyte recruitment into the airway, without any suppressive effects on peripheral blood leukocytes or bone marrow leukocytes, in contrast to the glucocorticoids.

International Immunopharmacology published new progress about Antigens Role: ADV (Adverse Effect, Including Toxicity), BIOL (Biological Study). 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Recommanded Product: YM-90709.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider