H-151
目录号 : GC34610
H-151是STING的低分子量拮抗剂,可阻断激活诱导的STING棕榈酰化,对STING信号传导有显著抑制作用,可用于自身炎症性疾病的研究。
Cas No.:941987-60-6
Sample solution is provided at 25 µL, 10mM.
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H-151 is a low MW antagonist of STING, which blocks the activation-induced palmitoylation of STING, and exhibits significant inhibitory effects on STING signalling H-151 can be used in the study of autoinflammatory diseases[1-2].
H-151(1 µM; 6 h) exerts anti-psoriasis effect through inhibiting STING/NF-κB signalling[3]. H-151(2.5 µM; 24h) improved the inflammation of peripheral blood mononuclear cells and Coatomer complex I (COPI)-deficient cell lines in patients with COPA syndrome[4].
H-151(250 /500 mg/kg; on the shaved back and right ear;5days) displayed anti-inflammatory activity in both keratinocytes and immune cells, and decreased the severity of psoriatic response in vivo[3]. H-151 downregulated the expression of granzymes and the pro-inflammatory cytokines IL-1β, IL-6, IL-15, IL-23A, and IFN-γ, and induced a pro-resolution macrophage phenotypes in ALS patients [5]. Administration of H-151 alleviated pulmonary edema, hemorrhage, thickening of the alveolar septum and infiltration of inflammatory cells; DNA damage in pulmonary tissue; and disruption of intercellular junctions in LPS-induced ALI [6]. H-151(750 nmol; i.p) treatment preserves myocardial function 28 days after myocardial infarction (MI)[7].
References:
[1]. Haag SM, Gulen MF, et,al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018 Jul;559(7713):269-273. doi: 10.1038/s41586-018-0287-8. Epub 2018 Jul 4. PMID: 29973723.
[2]. Li J, Lu Y, et,al. Blocking cGAS/STING signaling protects against sepsis-associated acute liver injury. Int Immunopharmacol. 2022 Dec;113(Pt A):109276. doi: 10.1016/j.intimp.2022.109276. Epub 2022 Oct 15. PMID: 36252490.
[3]. Pan Y, You Y, et,al. The STING antagonist H-151 ameliorates psoriasis via suppression of STING/NF-κB-mediated inflammation. Br J Pharmacol. 2021 Dec;178(24):4907-4922. doi: 10.1111/bph.15673. Epub 2021 Oct 30. PMID: 34460100.
[4]. Steiner A, Hrovat-Schaale K, et,al. Deficiency in coatomer complex I causes aberrant activation of STING signalling. Nat Commun. 2022 Apr 28;13(1):2321. doi: 10.1038/s41467-022-29946-6. PMID: 35484149; PMCID: PMC9051092.
[5]. Zamiri K, Kesari S, et,al. Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: Dimethyl fumarate and H-151 downregulate inflammatory cytokines in the cGAS-STING pathway. FASEB J. 2023 Aug;37(8):e23068. doi: 10.1096/fj.202300573R. PMID: 37436778; PMCID: PMC10619685.
[6]. Zhao J, Zhen N, et,al. NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury. Int J Mol Sci. 2023 Mar 7;24(6):5125. doi: 10.3390/ijms24065125. PMID: 36982193; PMCID: PMC10049640.
[7]. Hu S, Gao Y, et,al. The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction. Int Immunopharmacol. 2022 Jun;107:108658. doi: 10.1016/j.intimp.2022.108658. Epub 2022 Mar 9. PMID: 35278833.
H-151是STING的低分子量拮抗剂,可阻断激活诱导的STING棕榈酰化,对STING信号传导有显著抑制作用,可用于自身炎症性疾病的研究[1-2]。
H-151(1µM;6 h)通过抑制STING/NF-κB信号通路发挥抗银屑病作用[3]。H-151(2.5µM;24h)改善了COPA综合征患者外周血单核细胞和Coatomer complex I (COPI)缺陷细胞系的炎症反应[4]。
H-151(250 /500 mg/kg; on the shaved back and right ear;5days)在角质形成细胞和免疫细胞中均表现出抗炎活性,并在体内降低银屑病反应的严重程度[3]。H-151下调颗粒酶和促炎细胞因子IL-1β、IL-6、IL-15、IL-23A和IFN-γ的表达,诱导ALS患者巨噬细胞出现促溶解表型[5]。H-151可减轻肺水肿、出血、肺泡隔增厚及炎症细胞浸润;肺组织DNA损伤;以及LPS诱导ALI中细胞间连接的破坏[6]。H-151(750 nmol; i.p)治疗可在心肌梗死后28天保持心肌功能[7]。
| Cell experiment [1]: | |
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Cell lines |
THP-1 cells |
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Preparation Method |
Cells were pretreated with H-151 (1 µM) for 6 h, followed by stimulating with 2 ,3 -cGAMP (cGAMP, 10 µg/ml) for 12 h |
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Reaction Conditions |
1 µM; 6 h |
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Applications |
H-151 inhibited the induction of IFN-β mRNA expression triggered by cGAMP in THP-1 cells. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/c mice (model of psoriasis induced by imiquimod) |
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Preparation Method |
Mice were randomly divided into four groups (n = 8): control, model, model with 250 mg/kg H-151 (2.5% H-151 cream) and model with 500 mg/kg H-151 (5% H-151 cream) groups. A topical dose of 62.5 mg of 5% imiquimod cream was applied, once daily, to the shaved back and right ear in a ratio of 4:1 for five consecutive days to induce psoriasis-like skin inflammation. Control group was only treated with control cream (a mixture of wood fat and Vaseline in the ratio of one to one) on the shaved back and right ear in a ratio of 4:1 twice daily, 0.2 g per mice per treatment. The model group was treated with the control cream and imiquimod cream on the shaved back and right ear in a ratio of 4:1. Treatment groups were treated with H-151 creams (2.5% or 5% H-151 creams containing the same components as control cream) and imiquimod cream on the shaved back and right ear in a ratio of 4:1. Before imiquimod administration, the shaved back and right ear were topically treated with control cream or H-151 creams (250 or 500 mg/kg) in a ratio of 4:1, 0.2 g per mice. After imiquimod administration, another treatment with control cream or H-151 creams (250 or 500 mg/kg) was applied in the same manner mentioned above. The interval between all the treatments was 4 h. The body weight was measured every day. |
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Dosage form |
250 /500 mg/kg; on the shaved back and right ear;5days |
|
Applications |
H-151 ameliorates IMQ(imiquimod)-induced psoriasis-like dermatitis. |
|
References: [1]. Pan Y, You Y, et,al. The STING antagonist H-151 ameliorates psoriasis via suppression of STING/NF-κB-mediated inflammation. Br J Pharmacol. 2021 Dec;178(24):4907-4922. doi: 10.1111/bph.15673. Epub 2021 Oct 30. PMID: 34460100. |
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| Cas No. | 941987-60-6 | SDF | |
| Canonical SMILES | O=C(NC1=CNC2=C1C=CC=C2)NC3=CC=C(CC)C=C3 | ||
| 分子式 | C17H17N3O | 分子量 | 279.34 |
| 溶解度 | DMSO : 125 mg/mL (447.48 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 3.5799 mL | 17.8993 mL | 35.7987 mL |
| 5 mM | 0.716 mL | 3.5799 mL | 7.1597 mL |
| 10 mM | 0.358 mL | 1.7899 mL | 3.5799 mL |
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| 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 |
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| % 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，
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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。
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Quality Control & SDS
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- Purity: >98.00%
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