Semapimod  (Synonyms: CNI-1493 free base; CPSI-2364)

Semapimod, an inhibitor of proinflammatory cytokine production, can inhibit TNF-α, IL-1β, and IL-6. Semapimod inhibits TLR4 signaling (IC₅₀≈0.3 μM). Semapimod inhibits p38 MAPK and nitric oxide production in macrophages. Semapimod has potential in a variety of inflammatory and autoimmune disorders^[1][2][3].

Semapimod 导致巨噬细胞中 p38-MAPK 磷酸化、巨噬细胞炎症蛋白-1alpha、白细胞介素-6、单核细胞趋化蛋白-1 和细胞间粘附分子-1 的促炎基因表达以及中性粒细胞浸润显著降低。Semapimod 完全消除了肌层内一氧化氮的产生^[2]。
Semapimod 通过其对 TLR 伴侣蛋白 gp96 的影响使 TLR 信号脱敏。Semapimod tetrahydrochloride 在体外抑制 gp96 的 ATP 结合和 ATPase 活性 (IC₅₀≈0.2-0.4 μM)。Semapimod 通过其对 TLR 分子伴侣 gp96 的影响使 TLR 信号脱敏^[3]。
Semapimod (0-500 nM) 抑制小胶质细胞刺激的 GL261 侵袭^[4]。
Semapimod (0-10 µM) 不会影响血清刺激的胶质母细胞瘤细胞侵袭，即使浓度为 10 µM，这强调了 Semapimod 对单核细胞谱系细胞的选择性^[4]。
Semapimod (200 nM) 不会影响小胶质细胞刺激的胶质母细胞瘤细胞增殖^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Semapimod (5 mg/kg；腹腔注射；每天一次，持续 2 周) 改善 Obese Zucker (OZ) 大鼠的内皮功能障碍^[1]。
Semapimod 恢复 AM 诱导的 akt 磷酸化和 cGMP OZ 大鼠的生产^[1]。
Semapimod（6 mg/kg/天，颅内注射 1 周）抑制体内胶质母细胞瘤细胞侵袭^[4]。
Semapimod（颅内给药，2 周）semapimos 与放疗联合使用可显着提高 GL261 荷瘤动物的存活率，但在没有放疗的情况下没有显着益处^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

744.90

C₃₄H₅₂N₁₈O₂

352513-83-8

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Nishimatsu H, et al. Blockade of endogenous proinflammatory cytokines ameliorates endothelial dysfunction in obese Zucker rats. Hypertens Res. 2008;31(4):737‐743.  [Content Brief]

  [2]. Wehner S, Set al. Inhibition of p38 mitogen-activated protein kinase pathway as prophylaxis of postoperative ileus in mice. Gastroenterology. 2009;136(2):619‐629.  [Content Brief]

  [3]. Wang J, et al. Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96. J Immunol. 2016;196(12):5130‐5137.  [Content Brief]

  [4]. Miller IS, et al. Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia. PLoS One. 2014 May 9;9(5):e95885.  [Content Brief]