(R)-IL-17 modulator 4
目录号 : GC65373
(R)-IL-17 modulator 4 是 IL-17 modulator 4 的 R 构型形式。 IL-17 modulator 4 是一种 IL-17 modulator 1 的前药。IL-IL-17 modulator 1是一种具有口服活性的，高效的 IL-17 调节剂。
Cas No.:2446804-29-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(R)-IL-17 modulator 4 is the R-configure of IL-17 modulator 4 . IL-17 modulator 4 is a prodrug of IL-17 modulator 1 . IL-17 modulator 1 is an orally active, highly efficacious IL-17 modulator[1].
[1]. Kevin Neil Dack, et al. Amino-acid anilides as small molecule modulators of il-17. WO2020127685A1.
| Cas No. | 2446804-29-9 | SDF | Download SDF |
| 分子式 | C27H34N6O2 | 分子量 | 474.6 |
| 溶解度 | DMSO : 100 mg/mL (210.70 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.107 mL | 10.5352 mL | 21.0704 mL |
| 5 mM | 0.4214 mL | 2.107 mL | 4.2141 mL |
| 10 mM | 0.2107 mL | 1.0535 mL | 2.107 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
S100A gene family: immune-related prognostic biomarkers and therapeutic targets for low-grade glioma
Aging (Albany NY) 2021 Jun 8;13(11):15459-15478.PMID:34148033DOI:10.18632/aging.203103.
Background: Despite the better prognosis given by surgical resection and chemotherapy in low-grade glioma (LGG), progressive transformation is still a huge concern. In this case, the S100A gene family, being capable of regulating inflammatory responses, can promote tumor development. Methods: The analysis was carried out via ONCOMINE, GEPIA, cBioPortal, String, GeneMANIA, WebGestalt, LinkedOmics, TIMER, CGGA, R 4.0.2 and immunohistochemistry. Results: S100A2, S100A6, S100A10, S100A11, and S100A16 were up-regulated and S100A1 and S100A13 were down-regulated in LGG compared to normal tissues. S100A3, S100A4, S100A8, and S100A9 expression was up-regulated during the progression of glioma grade. In addition, genetic variation of the S100A family was high in LGG, and the S100A family genes mostly function through IL-17 signaling pathway, S100 binding protein, and inflammatory responses. The TIMER database also revealed a relationship between gene expression and immune cell infiltration. High expression of S100A2, S100A3, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, S100A13, and S100A16 was significantly associated with poor prognosis in LGG patients. S100A family genes S100A2, S100A3, S100A6, S100A10, and S100A11 may be prognosis-related genes in LGG, and were significantly associated with IDH mutation and 1p19q codeletion. The immunohistochemical staining results also confirmed that S100A2, S100A3, S100A6, S100A10, and S100A11 expression was upregulated in LGG. Conclusion: The S100A family plays a vital role in LGG pathogenesis, presumably facilitating LGG progression via modulating inflammatory state and immune cell infiltration.
Homeostatic (IL-7) and effector (IL-17) cytokines as distinct but complementary target for an optimal therapeutic strategy in inflammatory bowel disease
Curr Opin Gastroenterol 2009 Jul;25(4):306-13.PMID:19448533DOI:10.1097/MOG.0b013e32832bc627.
Purpose of review: This review focuses on CD4+ T cells involved in the mediation of inflammatory tissue damage in murine models of inflammatory bowel diseases (IBDs). In particular, we describe the distinct roles of the homeostatic cytokine IL-7, which is essential to the maintenance of colitogenic memory CD4+ cells, and the newly discovered effector cytokine IL-17. We also discuss the close correlation between colitogenic Th17-type CD4+ T cells and inducible CD4+CD25+Foxp3+ regulatory T cells. Recent findings: IBDs are characterized by wasting and chronic intestinal inflammation induced by many different cytokine-mediated pathways. It is clearly recognized that medical and surgical interventions do not cure Crohn's disease because relapse is the rule after remission. Until a few years ago, IBD was classified into Th1-dependent, that is, Crohn's disease, and Th2-dependent, that is, ulcerative colitis, phenotypes. However, in recent years, it has been shown that new T-cell subclasses, that is, Th17 and regulatory T cells (T(R)), exist independently of Th1 and Th2 and that they play a central role in modulating IBD. Summary: The persistence of IL-7-dependent colitogenic memory CD4+ T cells is critical to the maintenance of experimental colitis. On the other hand, though Th1 and Th2 colitogenic memory CD4+ cells exist, in recent years the central role of IL-17-producing Th17-type cells in IBD has attracted renewed interest. The development of molecularly targeted therapies aimed at a variety of different Th-dependent pathogenic mechanisms may represent a novel approach to IBD therapy.
Predictive role of IL-17A/IL-10 ratio in persistent asthmatic patients on vitamin D supplement
Immunobiology 2019 Nov;224(6):721-727.PMID:31570180DOI:10.1016/j.imbio.2019.09.005.
Asthma is an airway inflammatory disorder. Vitamin (Vit) D is a potent immuno-modulator. It suppresses Interleukin (IL)-17 and induces IL-10. This study aims to investigate the role of IL-17A and IL-10 in predicting asthma control in case of Vit D supplementation. Seventy-nine patients enrolled in this study (42 patients received Vit D supplement and 37 patients did not receive the supplement). The enrolled patients were assessed at the beginning of this study and after 3 months. At the end of the study, there was a significant improvement in pulmonary function parameters in the Vit D supplemented group when compared to both the baseline values and the non-supplemented group. There was a significant decrease in serum IL-17A levels and a significant increase in serum IL-10 levels in comparison with the baseline values (p < 0.0001). The highest correlation of FEV1% improvement percentage was associated with the baseline IL-17A/IL-10 ratio (R = 0.65; p < 0.0001). The IL-17A/IL-10 ratio at a cutoff ≥ 2.66 had a sensitivity of 72.2% and a specificity of 83.3%. The IL-17A/IL-10 ratio had an adjusted odds ratio = 4.66 (p = 0.04). Vit D supplementation reduces the serum IL-17A levels and elevates the serum IL-10 levels in persistent asthmatic patients. So, Vitamin D can be used as an adjunct therapy side by side with the conventional asthma therapy. The IL-17A/IL-10 ratio seems to be a possible predictive biomarker for asthma improvement in patients depending on Vit D supplementation.
Galectin-3 mediated risk of inflammation in stable schizophrenia, with only possible secondary consequences for cognition
World J Psychiatry 2022 Sep 19;12(9):1183-1193.PMID:36186503DOI:10.5498/wjp.v12.i9.1183.
Background: Evidence suggests that cytokines cause immune disturbances, shape immunological sequelae later in life, and modulate the risk of schizophrenia (SC). Galectin-3 (Gal-3), a multifaceted molecule of the glycan family, is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes, which are major producers of cytokines. We have previously reported elevated serum Gal-3 levels in stable SC patients. However, Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC. Aim: To investigate the relationship between serum Gal-3 levels and cognitive performance, serum cytokines, and white blood cell count in three-month stably treated SC patients. Methods: Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this case-control and correlational study. Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment. The results of previously measured serum levels of Gal-3, interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), tumor necrosis factor-alpha (TNF-α), IL-6 and IL-17 were used for further statistical analyses, and IL-4, IL-23, IL-1β and transforming growth factor-beta (TGF-β) were now additionally measured with a sensitive enzyme-linked immunosorbent assay. The number of leukocytes in the blood and the percentage of neutrophils, lymphocytes, and monocytes were determined with a standardized routine measurement procedure (Sysmex Technology). Statistical analyses were performed using SPSS 20.0 software. Results: We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients. A positive correlation was found between the levels of Gal-3 and TNF-α (R = 0.476; P = 0.012), Gal-3 and IL-23 (R = 0.417; P = 0.031), and Gal-3 and sST2 (R = 0.402; P = 0.038). The binary logistic model, which included all nine cytokines measured in this patient sample, indicated the particular role of Gal-3 and TGF-β in the duration of SC. In the stabilization phase of SC, we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes (R = -0.449; P < 0.019). Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose (F: 4.467; P < 0.045; R 2 = 0.396). Conclusion: The combined activity of Gal-3 and proinflammatory cytokines, TGF-β downregulation and lower counts of leukocytes influence the SC duration. Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.
Maternal fatty acid desaturase genotype correlates with infant immune responses at 6 months
Br J Nutr 2015 Sep 28;114(6):891-8.PMID:26283408DOI:10.1017/S0007114515002561.
Breast milk long-chain PUFA (LCPUFA) have been associated with changes in early life immune responses and may modulate T-cell function in infancy. We studied the effect of maternal fatty acid desaturase (FADS) genotype and breast milk LCPUFA levels on infants' blood T-cell profiles and ex vivo-produced cytokines after anti-CD3/CD28 stimulation of peripheral blood mononuclear cells in 6-month-old infants from the Copenhagen Prospective Study of Asthma in Childhood birth cohort. LCPUFA concentrations of breast milk were assessed at 4 weeks of age, and FADS SNP were determined in both mothers and infants (n 109). In general, breast milk arachidonic acid (AA) levels were inversely correlated with the production of IL-10 (R -0.25; P=0.004), IL-17 (R -0.24; P=0.005), IL-5 (R -0.21; P=0.014) and IL-13 (R -0.17; P=0.047), whereas EPA was positively correlated with the counts of blood regulatory T-cells and cytotoxic T-cells and decreased T-helper cell counts. The minor FADS alleles were associated with lower breast milk AA and EPA, and infants of mothers carrying the minor allele of FADS SNP rs174556 had higher production of IL-10 (R -0.23; P=0.018), IL-17 (R -0.25; P=0.009) and IL-5 (R -0.21; P=0.038) from ex vivo-activated immune cells. We observed no association between T-cell distribution and maternal or infant FADS gene variants. We conclude that increased maternal LCPUFA synthesis and breast milk AA are associated with decreased levels of IL-5, IL-13 (type-2 related), IL-17 (type-17 related) and IL-10 (regulatory immune responses), but not with interferon-γ and TNF-α, which could be due to an effect of the maternal FADS variants on the offspring immune response transferred via breast milk LCPUFA.