Paquinimod (ABR 25757)
(Synonyms: 帕奎莫德; ABR 25757) 目录号 : GC31346Paquinimod (ABR-215757) 结合 S100A9 并抑制其与 TLR4/MD2 和 RAGE 的相互作用。
Cas No.:248282-01-1
Sample solution is provided at 25 µL, 10mM.
Paquinimod (ABR-215757) binds S100A9 and inhibits its interaction with TLR4/MD2 and RAGE[1-2].
The addition of paquinimod(350 μM paquinimod;30 min preincubated) significantly inhibited the up-regulated levels of IL-6 and IL-8 protein in synovium due to S100A9, but had no inhibitory effect on TNF-α[7].
Mice prophylactically treated with paquinimod(10 mg/kg/day;14days;added into the drinking water) exhibited detectable but mitigated signs of colitis, as determined by a reduced trend in weight loss, reduced colonic shortening and inflammation in the colons compared to DSS-only treated mice. Paquinimod treatment also prevented the upregulation of Lcn2 and S100A8/A9 in the brain in DSS-treated mice[3]. In a meningitis model, MRP14-deficient mice showed a better resolution of inflammation during antibiotic therapy. Treatment with the MRP14 antagonist paquinimod(10 mg/kg) reduced inflammation and disease severity significantly, reaching levels comparable to those achieved after genetic depletion of MRP14[4]. Preventive treatment with the paquinimod (ABR-215757) (25 mg/kg;5days;added into the drinking water) during the first 5 days after induction of experimental autoimmune encephalomyelitis is sufficient to significantly ameliorate disease symptoms[5]. Paquinimod treatment can significantly inhibit progression of insulitis to T1D in the NOD mouse[6].
References:
[1]. Bj?rk P, Bj?rk A,et,al. Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol. 2009 Apr 28;7(4):e97. doi: 10.1371/journal.pbio.1000097. PMID: 19402754; PMCID: PMC2671563.
[2]. Gong H, Su WJ, et,al.Hippocampal Mrp8/14 signaling plays a critical role in the manifestation of depressive-like behaviors in mice. J Neuroinflammation. 2018 Sep 4;15(1):252. doi: 10.1186/s12974-018-1296-0. PMID: 30180864; PMCID: PMC6122683.
[3]. Talley S, Valiauga R, et,al.DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod. J Neuroinflammation. 2021 Nov 10;18(1):263. doi: 10.1186/s12974-021-02317-6. PMID: 34758843; PMCID: PMC8578918.
[4]. Wache C, Klein M, et,al.Myeloid-related protein 14 promotes inflammation and injury in meningitis. J Infect Dis. 2015 Jul 15;212(2):247-57. doi: 10.1093/infdis/jiv028. Epub 2015 Jan 20. PMID: 25605866.
[5]. Helmersson S, Sundstedt A, et,al.Amelioration of experimental autoimmune encephalomyelitis by the quinoline-3-carboxamide paquinimod: reduced priming of proinflammatory effector CD4(+) T cells. Am J Pathol. 2013 May;182(5):1671-80. doi: 10.1016/j.ajpath.2013.01.032. Epub 2013 Mar 16. PMID: 23506849.
[6]. Tahvili S, T?rngren M, et,al. Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse. PLoS One. 2018 May 9;13(5):e0196598. doi: 10.1371/journal.pone.0196598. PMID: 29742113; PMCID: PMC5942776.
[7]. Schelbergen RF, Geven EJ, et,al.Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in experimental collagenase-induced osteoarthritis. Ann Rheum Dis. 2015 Dec;74(12):2254-8. doi: 10.1136/annrheumdis-2014-206517. Epub 2015 May 12. PMID: 25969431.
Paquinimod (ABR-215757) 结合 S100A9 并抑制其与 TLR4/MD2 和 RAGE 的相互作用[1-2]。
添加帕喹莫德(350 μM 帕喹莫德;30 分钟预孵育)可显着抑制 S100A9 引起的滑膜中 IL-6 和 IL-8 蛋白水平上调,但对 TNF-α 无抑制作用 [7].
用帕喹莫德(10 毫克/千克/天;14 天;添加到饮用水中)进行预防性治疗的小鼠表现出可检测到但减轻的结肠炎迹象,这是由体重减轻趋势减少、结肠缩短和结肠炎症减少来确定的与仅接受 DSS 治疗的小鼠相比。 Paquinimod 治疗还阻止了 DSS 治疗小鼠大脑中 Lcn2 和 S100A8/A9 的上调[3]。在脑膜炎模型中,MRP14 缺陷小鼠在抗生素治疗期间表现出更好的炎症消退。使用 MRP14 拮抗剂帕喹莫德 (10 mg/kg) 治疗可显着降低炎症和疾病严重程度,达到与 MRP14 基因缺失后达到的水平相当[4]。在诱导实验性自身免疫性脑脊髓炎后的前 5 天内,使用帕喹莫德 (ABR-215757)(25 mg/kg;5 天;添加到饮用水中)进行预防性治疗足以显着改善疾病症状[5]。帕喹莫德治疗可显着抑制 NOD 小鼠胰岛炎进展为 T1D[6]。
Tissue experiment [1]: | |
Tissue |
Human synovium |
Preparation Method |
Incubated osteoarthritis (OA) synovium with human S100A916 and paquinimod and measured the protein release. |
Reaction Conditions |
350 µM paquinimod;30 min preincubated |
Applications |
S100A9 clearly upregulated IL-6, IL-8 and TNF-α protein levels in OA synovia, and addition of paquinimodsignificantly inhibited this upregulation for IL-6 and IL-8, but not TNF-α. |
Animal experiment [2]: | |
Animal models |
IQAD Tg C57Bl/6 mice |
Preparation Method |
Mice were treated with 10 mg/kg/day paquinimod, added into the drinking water starting 7 days prior to the addition of DSS and continued during the DSS regimen. Control mice received the same dose of paquinimod for 14 days. In all experiments, water was changed twice a week. |
Dosage form |
10 mg/kg/day paquinimod;14days;added into the drinking water |
Applications |
Mice prophylactically treated with paquinimod exhibited detectable but mitigated signs of colitis, as determined by a reduced trend in weight loss, reduced colonic shortening and inflammation in the colons compared to DSS-only treated mice. Paquinimod treatment also prevented the upregulation of Lcn2 and S100A8/A9 in the brain in DSS-treated mice. |
References: [1].Schelbergen RF, Geven EJ, et,al.Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in experimental collagenase-induced osteoarthritis. Ann Rheum Dis. 2015 Dec;74(12):2254-8. doi: 10.1136/annrheumdis-2014-206517. Epub 2015 May 12. PMID: 25969431. [2]. Talley S, Valiauga R, et,al.DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod. J Neuroinflammation. 2021 Nov 10;18(1):263. doi: 10.1186/s12974-021-02317-6. PMID: 34758843; PMCID: PMC8578918. |
Cas No. | 248282-01-1 | SDF | |
别名 | 帕奎莫德; ABR 25757 | ||
Canonical SMILES | O=C(C1=C(O)C2=C(C=CC=C2CC)N(C)C1=O)N(CC)C3=CC=CC=C3 | ||
分子式 | C21H22N2O3 | 分子量 | 350.41 |
溶解度 | DMSO : ≥ 125 mg/mL (356.72 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.8538 mL | 14.269 mL | 28.538 mL |
5 mM | 0.5708 mL | 2.8538 mL | 5.7076 mL |
10 mM | 0.2854 mL | 1.4269 mL | 2.8538 mL |
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2.
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