GSK121 (trifluoroacetate salt)
目录号 : GC43788
A PAD4 inhibitor
Cas No.:1652591-80-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Protein arginine deiminase 4 (PAD4) mediates the transformation of protein arginine into citrulline. Citrullination of proteins has normal roles in gene regulation and pathological roles in immunological and inflammatory diseases. GSK121 is the initial compound identified in a screen for PAD4 inhibitors and was optimized to produce the more potent PAD4 inhibitors, GSK484 and GSK199 . GSK121 was shown to inhibit the citrullination of PAD4 target proteins in a functional assay with an IC50 value of 3.2 µM.
| Cas No. | 1652591-80-4 | SDF | |
| Canonical SMILES | NC1CN(C(C2=CC(N=C(C3=CC(C=CC=C4)=C4N3C)N5C)=C5C=C2)=O)CCC1.FC(F)(C(O)=O)F | ||
| 分子式 | C23H25N5O•CF3COOH | 分子量 | 501.5 |
| 溶解度 | DMF: 30 mg/ml,DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol: 30 mg/ml,PBS (pH 7.2): 10 mg/ml,PBS (pH 7.2): 10 mg/ml | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.994 mL | 9.9701 mL | 19.9402 mL |
| 5 mM | 0.3988 mL | 1.994 mL | 3.988 mL |
| 10 mM | 0.1994 mL | 0.997 mL | 1.994 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。
Critical Neurotransmitters in the Neuroimmune Network
Front Immunol 2020 Aug 21;11:1869.PMID:32973771DOI:10.3389/fimmu.2020.01869.
Immune cells rely on cell-cell communication to specify and fine-tune their responses. They express an extensive network of cell communication modes, including a vast repertoire of cell surface and transmembrane receptors and ligands, membrane vesicles, junctions, ligand and voltage-gated ion channels, and transporters. During a crosstalk between the nervous system and the immune system these modes of cellular communication and the downstream signal transduction events are influenced by neurotransmitters present in the local tissue environments in an autocrine or paracrine fashion. Neurotransmitters thus influence innate and adaptive immune responses. In addition, immune cells send signals to the brain through cytokines, and are present in the brain to influence neural responses. Altered communication between the nervous and immune systems is emerging as a common feature in neurodegenerative and immunopathological diseases. Here, we present the mechanistic frameworks of immunostimulatory and immunosuppressive effects critical neurotransmitters - dopamine (3,4-dihydroxyphenethylamine), serotonin (5-hydroxytryptamine), substance P (trifluoroacetate salt powder), and L-glutamate - exert on lymphocytes and non-lymphoid immune cells. Furthermore, we discuss the possible roles neurotransmitter-driven neuroimmune networks play in the pathogenesis of neurodegenerative disorders, autoimmune diseases, cancer, and outline potential clinical implications of balancing neuroimmune crosstalk by therapeutic modulation.
PAR2 promotes M1 macrophage polarization and inflammation via FOXO1 pathway
J Cell Biochem 2019 Jun;120(6):9799-9809.PMID:30552714DOI:10.1002/jcb.28260.
Macrophages polarization plays essential but different roles in most diseases such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Our previous study revealed that protease-activated receptor 2 (PAR2), a G-protein coupled receptor influenced macrophage function, but little is known regarding the regulation of macrophage polarization process and its potential mechanisms. In the present study, bone marrow-derived macrophages (BMDM) isolated from C57/BL6 mice and cultured with L929-conditional medium and murine macrophage cell line RAW264.7 were used to study the function of PAR2 activation in vitro. BMDM was stimulated by the small molecular PAR2 agonist, 2-furoyl-LIGRLO-amide trifluoroacetate salt, followed by transcription factor microarray to screen the significantly activated signaling pathways under PAR2 activation. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression of targeted genes and transcription factors. Immunofluorescence was used to observe the subcellular distribution of transcription factors. Our results demonstrated that M1-like polarization was presented by PAR2 agonist treatment with significant upregulation of interleukin-1β, interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α in BMDM and RAW264.7. Microarray identified forkhead box protein O1 (FOXO1) was significantly increased under PAR2 agonist stimulation, which was confirmed by qPCR and Western blot analysis. Immunofluorescence demonstrated that increased FOXO1 accumulated in the nucleus, which is necessary to promote transcription for targeted genes. We further knocked down FOXO1 expression using small interfering RNA, which alleviated PAR2-induced proinflammatory gene expression. The PAR2/FOXO1 pathway mediated stimulation of proinflammatory genes was further confirmed by tryptase, an endogenous ligand of PAR2. In conclusion, this study demonstrated that PAR2 activation-induced M1 polarization and inflammation through the FOXO1-dependent pathway.
Antifungal Activity of Amphiphilic Perylene Bisimides
Molecules 2022 Oct 14;27(20):6890.PMID:36296485DOI:10.3390/molecules27206890.
Perylene-based compounds, either naturally occurring or synthetic, have shown interesting biological activities. In this study, we report on the broad-spectrum antifungal properties of two lead amphiphilic perylene bisimides, compounds 4 and 5, which were synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride by condensation with spermine and an ammonium salt formation. The antifungal activity was evaluated using a collection of fungal strains and clinical isolates from patients with onychomycosis or sporotrichosis. Both molecules displayed an interesting antifungal profile with MIC values in the range of 2-25 μM, being as active as several reference drugs, even more potent in some particular strains. The ammonium trifluoroacetate salt 5 showed the highest activity with a MIC value of 2.1 μM for all tested Candida spp., two Cryptococcus spp., two Fusarium spp., and one Neoscytalidium spp. strain. Therefore, these amphiphilic molecules with the perylene moiety and cationic ammonium side chains represent important structural features for the development of novel antifungals.
L-arginine trifluoroacetate salt bridges in its solid state compound: the low-temperature three dimensional structural determination of L-arginine bis(trifluoroacetate) crystal and its vibrational spectral analysis
Spectrochim Acta A Mol Biomol Spectrosc 2011 Dec;83(1):39-45.PMID:21893427DOI:10.1016/j.saa.2011.07.008.
Structural varieties of L-arginine trifluoroacetate (abbreviated as LATF) and L-arginine bis(trifluoroacetate), LABTF, in the solid state compounds were observed and analyzed by the nuclear magnetic resonance (NMR) spectroscopy. The guanidinium-carboxylate interaction plays an important role involving in the crystal structure construction. Conformational changes of L-Arg(+) and L-Arg(2+) cations result from the intrinsic structural difference by hydrogen bonding and electrostatic interactions. The low-temperature structure of its crystalline salt, L-arginine bis(trifluoroacetate), was determined to describe the hydrogen bonding interactions. In comparison with the crystal structure at room temperature, the low-temperature L-Arg(2+) cations present tiny conformational difference and the rotational disorder of CF(3) group disappears. FT-IR and Raman spectra were investigated and hydrogen bonding interactions were analyzed on the basis of its vibrational spectra. Results indicate that this type interaction is greatly contributive to the structural features and vibrational spectral properties.
Peptide nanotube nematic phase
Langmuir 2009 Apr 21;25(8):4262-5.PMID:19275132DOI:10.1021/la804175h.
The self-assembly of the trifluoroacetate salt of the short peptide (ala)6-lys (A6K) in water has been investigated by cryo-transmission electron microscopy and small-angle X-ray scattering. For concentrations below ca. 12%, the peptide does not self-assemble but forms a molecularly dispersed solution. Above this critical concentration, however, A6K self-assembles into several-micrometer-long hollow nanotubes with a monodisperse cross-sectional radius of 26 nm. Because the peptides carry a positive charge, the nanotubes are charge-stabilized. Because of the very large aspect ratio, the tubes form an ordered phase that presumably is nematic.