Naamidine J

Naamidine J is an imidazole-type alkaloids discovered in a sponge. Naamidine J inhibits inflammation by binding to the protein CSE1L (K_D = 5.41 μM). Namidine J significantly inhibits the expression of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6, and upregulates anti-inflammatory factors such as CD206 and Arg-1. Namidine J inhibits PD-L1 and shows antitumor activity. Namidine J significantly reduces pulmonary tissue edema, inflammatory cell infiltration and cytokine storm in mice. Namidine J can be used for the research on the immune microenvironment of acute lung injury and tumors^[1][2].
Naamidine J (5 μM, 24 h) was cytotoxic to K562 cells with an IC₅₀ of 11.3 μM, but non-toxic to macrophages and RKO cells (IC₅₀ > 40 μM) ^[1][2].

Naamidine J (10 μM, 24 h) reduced PD-L1 expression in RKO cells and PDAC cells ^[1][3].

Naamidine J (1-5 μM, 5 h) inhibited LPS-induced inflammatory responses in RAW264.7 macrophages ^[2].

Naamidine J (5 μM, 5 h) inhibited CSE1L-mediated SP1 nuclear translocation in LPS-induced macrophages ^[2].

Naamidine J (10 μM, 24 hours) can restore the cytotoxicity of CD8⁺ T cells and significantly reduce the survival rate of PDAC cells (MIA-PaCa2, BxPC-3)^[3].

References:
[1]. Fu PP, et al. Bioactivity-Driven Synthesis of the Marine Natural Product Naamidine J and Its Derivatives as Potential Tumor Immunological Agents by Inhibiting Programmed Death-Ligand 1. J Med Chem. 2023 Apr 27;66(8):5427-5438.
[2]. Gao CL, et al. Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury. J Am Chem Soc. 2024 Oct 16;146(41):28384-28397.
[3]. Chen E, et al. NAT10 regulates tumor progression and immune microenvironment in pancreatic ductal adenocarcinoma via the N4-acetylated LAMB3-mediated FAK/ERK pathway. Cancer Commun (Lond). 2025 Sep;45(9):1162-1187.

Naamidine J 是一种在海绵中发现的咪唑类生物碱。Naamidine J 通过与蛋白 CSE1L (K_D = 5.41 μM) 结合来抑制炎症。Namidine J 显著抑制促炎因子 (TNF-α、IL-1β 和 IL-6) 的表达，并上调抗炎因子 (CD206 和 Arg-1)。Namidine J 抑制 PD-L1 并展示出抗癌活性。Namidine J 显著减轻小鼠肺组织水肿、炎症细胞浸润和细胞因子风暴。Naamidine J 可用于急性肺损伤和肿瘤的免疫微环境的研究。
Naamidine J (5 μM, 24 小时) 对 K562 细胞具有细胞毒性，IC₅₀ 为 11.3 μM，但对巨噬细胞和 RKO 细胞无毒性 (IC₅₀ > 40 μM)。
Naamidine J (10 μM，24 小时) 可降低 RKO 细胞和 PDAC 细胞中的 PD-L1 表达。
Naamidine J (1-5 μM, 5 小时) 可抑制 LPS 诱导的 RAW264.7 巨噬细胞中的炎症反应。
Naamidine J (5 μM, 5 小时) 可抑制 CSE1L 介导的转录因子 SP1 核易位。 LPS 诱导的巨噬细胞。
Naamidine J (10 μM，24 小时) 可恢复 CD8⁺ T 细胞的细胞毒性，并显著降低 PDAC 细胞 (MIA-PaCa2、BxPC-3) 的存活率。