il-18

hydrocotarnine 是 Cbl 的抑制剂。

Aletekitug 是一种靶向 IL-18 的人源化抗体，可用于研究炎症性肠病。

Remibrutinib 是有效的、口服具有活力的 bruton tyrosine kinase 抑制剂 (IC50:1 nM)，在血液中抑制 BTK 活性的 IC50的值为 0.23 μM。它具有研究慢性荨麻疹的潜力。

JNJ-54175446 (JNJ-5446) 是一种具有中枢神经系统渗透性和选择性的 P2X7 受体拮抗剂，可减弱小胶质细胞 IL-1β IL-18 的释放，可用于研究抑郁症。

Lyn peptide inhibitor acetate(222018-18-0 free base) 是一种有效的细胞渗透性 Lyn 偶联 IL-5 受体信号通路抑制剂，同时保持其他信号完整。它阻断 Lyn 活化并抑制 Lyn 酪氨酸激酶与 IL-3 GM-CSF IL-5 受体的 βc 亚基的结合。它可用于哮喘、过敏和其他嗜酸性粒细胞疾病的研究。

BAA473 是胆汁酸类似物，是一种强效的吡喃类炎症小体激活剂。BAA473可通过激活髓样和肠上皮细胞中的炎症小体来诱导白细胞介素（ IL-18 ）的分泌。

Pralnacasan inhibits proinflammatory cytokines IL-18, IL-1β , and IFN-γ. Pralnacasan is an effective, non-peptide, and orally active interleukin-1β converting enzyme inhibitor (Ki: 1.4 nM). Pralnacasan has the potential for osteoarthritis and rheumatoid a

PQA-18 是p21激活激酶2（PAK2；IC50 = 10 nM）的有效抑制剂，并作为Ppc-1（产品编号42352）衍生物展现出免疫抑制特性。该化合物能够降低由刀豆A（产品编号14951）刺激的Jurkat T细胞中IL-2的生成（IC50 = 400 nM）。在应用0.1% PQA-18的情况下，NC Nga小鼠模型显示异位性皮炎的严重程度、血清IgE水平及皮肤厚度有所减轻。此外，0.05%的剂量可有效减少该小鼠模型中皮肤神经纤维的密度。PQA-18（4 mg kg）还在大鼠小肠移植模型中显著提高了移植物的存活率。

Nrf2 activator 18 (Compound 11a) 是一种口服有效的Keap1 Nrf2 HO-1信号通路激活剂，能够促进Nrf2的核转移并增强抗氧化功能。Nrf2 activator 18 能抑制IL-6的释放，IC50为4.816 μM。在小鼠PM2.5引起的肺损伤模型中，该化合物表现出抗炎活性。

LC-04-045 是NEK7 (NIMA 相关激酶 7) 的分子胶降解剂 (MGD)。在 MOLT-4 细胞中，LC-04-045 显示出强效的NEK7降解活性，DC50为7 nM，Dmax达到90%。该化合物在蛋白质组范围内对NEK7具有高度选择性，并通过泛素-蛋白酶体系统 (UPS) 降解NEK7，依赖于NEK7中包含甘氨酸 57 (G57) 的降解基序。LC-04-045 有效抑制IL-1β和IL-18的分泌，IC50值分别为33.03 nM和32.99 nM，可用于炎症性疾病的研究。

C6 L-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides., C6 L-threo Ceramide is cytotoxic to U937 cells in vitro (IC50 = 18 μM). It is metabolically inactive and, unlike C6 L-erythro ceramide , C6 L-threo ceramide cannot be converted to C6 glucosylceramide by ceramide glucosyltransferase. C6 L-threo Ceramide enhances IL-4 production induced by phorbol 12-myristate 13-acetate in EL4 T cells when used at a concentration of 10 μM.

Ac-YVAD-CMK (Ac-Tyr-Val-Ala-Asp-CMK) 是一种选择性的、不可逆的Caspase-1抑制剂，并能抑制焦亡作用、IL-1β和IL-18。Ac-YVAD-CMK 显示出神经保护和抗炎的能力。

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

PE(18:1(9Z) 0:0) 是一种天然存在的溶血磷脂，是缩醛磷脂溶血磷脂酰乙醇胺的类似物。 PE(18:1(9Z) 0:0) 以浓度依赖性方式诱导 PC12 大鼠神经元细胞中细胞内钙的瞬时增加。 PE(18:1(9Z) 0:0) 增加 IL-4 和 IL-2 的产生，但不增加 IFN-γ 的产生。 在小鼠血清中，PE(18:1(9Z) 0:0)（1 μg 动物）诱导 T 辅助细胞 2 反应。 在寒冷暴露三天后，小鼠肩胛间棕色脂肪组织中的 PE(18:1(9Z) 0:0) 水平增加。

C18 Phytoceramide (t18:0 18:0) (Cer(t18:0 18:0)) is a bioactive sphingolipid found in S. cerevisiae, wheat grains, and the stratum corneum layer of mammalian epidermis. Cer(t18:0 18:0) is composed of a phytosphingosine backbone amine-linked to a C18 fatty acid chain. Cer(t18:0 18:0) has a role in regulation of apoptosis, cell differentiation, proliferation of smooth muscle cells, and inhibition of the mitochondrial respiratory chain. It also inhibits expression of the allergic cytokines IL-4, TNF-α, and transcription factors c-Jun and NF-κB in histone-stimulated murine skin tissue. Formulations containing cer(t18:0 18:0) have been used used in cosmetics as a skin protectants as they reduce water loss to prevent epidermal dehydration and irritation.

C6 D-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides., C6 D-threo Ceramide is cytotoxic to U937 cells in vitro (IC50 = 18 μM). It is metabolically inactive and, unlike C6 L-erythro ceramide , C6 D-threo ceramide cannot be converted to C6 glucosylceramide by ceramide glucosyltransferase. C6 D-threo Ceramide promotes survival of isolated rat spinal neurons when used at concentrations up to 2.5 μM but induces cell death at concentrations greater than 5 μM. It enhances IL-4 production induced by phorbol 12-myristate 13-acetate in EL4 T cells when used at a concentration of 10 μM.

LDN 0088050 is selectivity adipocyte fatty acid binding protein (AFABP, FABP4) inhibitor with Ki values of 0.29 and 1.3 μM for FABP4 and FABP3, respectively. LDN 0088050 binds to FABP4 with a Kd of 2.05 μM[1]. Ki: 0.29 μM (FABP4), 1.3 μM (FABP3)[1]Kd: 2.05 μM (FABP4)[1] LDN 0088050 significantly inhibits LPS-induced expression of both TNFα and IL-6 in RAW264.7 cells[1]. [1]. Zhou Y, et al. The discovery of novel and selective fatty acid binding protein 4 inhibitors by virtual screening and biological evaluation. Bioorg Med Chem. 2016 Sep 15;24(18):4310-4317.

QS-21, an immunostimulatory saponin, is a powerful vaccine adjuvant that stimulates both Th2 humoral and Th1 cell-mediated immune responses by interacting with antigen presenting cells (APCs) and T cells. Additionally, QS-21 activates the NLRP3 inflammasome, leading to the release of cytokines IL-1β and IL-18, which are dependent on caspase-1.

IMMH001, also known as SYL930, is an orally active compound that exhibits potent selectivity as an agonist for the S1P1 receptor, which is the sphingosine-1-phosphate receptor 1. This compound effectively reduces the levels of various chemokines and proinflammatory cytokines, such as IL-1β, IL-5, IL-18, IP10, CCL3, and CCL5. IMMH001 finds utility in research focused on rheumatoid arthritis (RA) [1] [2].

Fc 11a-2 是一种苯并咪唑化合物，一种具有口服活性且有效的NLRP3炎症小体 (NLRP3inflammasome) 抑制剂。Fc 11a-2 通过抑制caspase-1的激活进而抑制 IL-1b IL-18 的激活来抑制NLRP3炎性体的形成。Fc 11a-2 可防止Dextran sulfate sodium(DSS) 诱导的小鼠实验性结肠炎。

SB-284851-BT 是一种 BRD4 p38α BRDT 抑制剂。SB-284851-BT 抑制BRD4-BD1(IC50=1.7 µM)、p38α(Kd=0.47 nM)、BRDT(1) (IC50=18 µM) 和BRD4(1) (IC50=3.7 µM)。SB-284851-BT 通过抑制p38α以减少IL-8的产生，抑制BRD4以下调癌症的c-Myc 和NF-κB 基因通路。SB-284851-BT 能与溴结构域和超末端结构域 (BET) 结合。

Soyacerebroside II exhibits ionophoretic activity for Ca2+ ion. Soyacerebrosides I and II have modulating the cellular immune response effects, they show obvious inhibitory activity on IL-18 secretion in human peripheral blood mononuclear cells (PBMC).

TLR9-IN-18 is a potent and selective TLR9 antagonist. TLR9-IN-18 suppresses the production of the proinflammatory cytokine IL-6 in a CpG-induced mouse model.

Camoteskimab (AVTX-007)为全人源、高亲和力抗IL-18单克隆抗体，展现于自身炎症性疾病研究潜力，包括成人斯蒂尔病(AOSD)。