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 leads to a significant decrease of p38-MAPK phosphorylation in macrophages, proinflammatory gene expression of macrophage inflammatory protein-1alpha, interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1, and neutrophil infiltration. Semapimod completely abrogated nitric oxide production within the tunica muscularis^[2].
Semapimod desensitizes TLR signaling via its effect on the TLR chaperone gp96. Semapimod tetrahydrochloride inhibits ATP-binding and ATPase activities of gp96 in vitro (IC₅₀≈0.2-0.4 μM). Semapimod desensitizes TLR signaling via its effect on the TLR chaperone gp96^[3].
Semapimod (0-500 nM) inhibits microglia-stimulated GL261 invasion^[4].
Semapimod (0-10 µM) dose not affect serum-stimulated glioblastoma cell invasion, even at 10 µM, underlining the selectivity of semapimod for cells from the monocytic lineage^[4].
Semapimod (200 nM) does not affect microglia-stimulated glioblastoma cell proliferation^[4].

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

Semapimod (5 mg/kg; i.p; daily for 2 weeks) ameliorates endothelial dysfunction in Obese Zucker (OZ) rats^[1].
Semapimod restores AM-induced akt phosphorylation and cGMP production in OZ rats^[1].
Semapimod (6 mg/kg/day, Intracranially for 1 week) inhibits glioblastoma cell invasion in vivo^[4].
Semapimod (intracranially administered, 2 weeks) semapimos strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation^[4].

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

744.90

C₃₄H₅₂N₁₈O₂

352513-83-8

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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]