experimental autoimmune encephalomyelitis

5J-4 是一种有效的钙释放激活钙通道 (CRAC) 和钙池操纵性钙内流(SOCE) 阻滞剂。 5J-4 减少 IL-17 的产生并降低 RORα 和 RORγt 的表达。

ASP-4058 是一种鞘氨醇磷酸受体 1 和 5 (S1P1 and S1P5) 的二代激动剂，具有选择性、安全性和口服活性。ASP-4058能改善小鼠实验性自身免疫性脑脊髓炎。

AMG-369 (AMG 247) 是一种 S1P1 S1P5 双重激动剂，可延缓延大鼠实验性自身免疫 性脑脊髓炎的发生。

BN201（OCS-05）是一种具有神经保护和髓鞘修复作用的药物，主要通过激活血清糖皮质激素激酶-2（SGK2）来发挥作用，进而激活FOXO3通路，促进神经元存活和髓鞘修复。主要用于治疗多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）等炎性神经疾病。BN201能够调节胰岛素生长因子1（IGF1）通路中的多个激酶并穿过血脑屏障。

MCC950 (CP-456773) 是NLRP3的选择性抑制剂，能够作用于BMDMs(IC50:7.5 nM) 和 HMDMs(IC50:8.1 nM)。

Cenerimod (ACT-334441) 是一种具有口服活性、选择性和高效性的磷酸鞘氨醇 1 受体（S1P1）激动剂（EC50：1 nM）。Cenerimod 对多种 S1P 的亚型具有抑制作用，可用于研究鼠类实验性自身免疫性脑脊髓炎 (EAE)和鼠类硬皮病。

Luzindole (N-0774) 是一种选择性褪黑素受体拮抗剂，可抑制实验性自身免疫性脑脊髓炎，有抗抑郁样活性。它优先靶向 MT2 (Mel1b)，对于人 MT2 和 MT1 的 Ki 值分别为 10.2 和 158 nM。

Nrf2 activator-12 (compound 10v) 在实验性自身免疫性脑脊髓炎小鼠模型中有效启动Nrf2 (EC50=83.5 nM)，显示出优异的药物属性，能逆转疾病的进展并减轻脱髓鞘现象。

ADWX 1 TFA 是一种新型肽类化合物，以1.89 pM的IC50强效抑制Kv1.3。该化合物特异性地抑制Kv1.3通道的活性，阻断初始钙信号传导和NF-κB的激活。在大鼠模型中，ADWX 1 TFA能有效改善experimental autoimmune encephalomyelitis (EAE)的症状。此外，该化合物广泛应用于研究T细胞介导的自身免疫性疾病。

BNN27 是 TrkA 受体 (TrkA receptor) 和 p75NTR 受体 (p75NTR receptor) 的激动剂，具备神经营养和抗凋亡特性。该化合物能够提升大鼠海马和前额叶皮质中的谷氨酸、GABA 和谷氨酰胺水平，同时改善谷氨酸的代谢。在小鼠肌萎缩侧索硬化症 (ALS) 模型中，BNN27 展示了神经保护效果；在实验性自身免疫性脑脊髓炎 (EAE) 模型中显示出抗炎能力，并在大鼠糖尿病模型中具有视网膜保护功能。此外，BNN27 还能透过血脑屏障。

RORγt inhibitor 4 (Compound 9a) 是一种口服活性且能够穿透中枢神经系统的RORγt抑制剂，用于改善实验性自身免疫性脑脊髓炎。

CA 074 是一种高效的组织蛋白酶B (cathepsin B) 抑制剂， Ki 值为2 to 5 nM。CA 074 抑制灵长类动物缺血性海马神经元死亡，可减轻 SJL J 小鼠诱导的实验性自身免疫性脑脊髓炎的视网膜病变和视神经炎。

Phenidone (1-phenyl-3-pyrazolidinone) 是可口服发环氧化酶和脂氧合酶双重抑制剂，可改善实验性自身免疫性脑脊髓炎大鼠的瘫痪，降低自发性高血压大鼠的血压，可用作照片显像剂。

NIBR-0213 是一种有效的选择性 S1P1 竞争性拮抗剂，有抗实验性自身免疫性脑脊髓炎的作用。在 GTPγ35S 试验中，它作用于人和大鼠S1P1的IC50分别为 2.0 nM 和 2.3 nM。

Ex26 (S1P1-IN-Ex26) 是一种具有选择性和高效性的 sphingosine 1-phosphate receptor 1 (S1P1) 拮抗剂，可破坏 SR-B1-S1PR1相互作用，抑制 S1P-S1PR1 信号转导。Ex26 可用于实验性自身免疫性脑脊髓炎、动脉粥样硬化和胃癌。

BMS-520 is a potent, selective S1P1 agonist that has shown impressive efficacy when administered orally in a rat model of arthritis and in a mouse model of experimental autoimmune encephalomyelitis (EAE) with multiple sclerosis.

Bacoside A has a possible anticancer activity that could be inducing cell cycle arrest and apoptosis through Notch pathway in GBM in vitro. It exerts cytoprotective efficacy by attenuation of ROS generated through oxidative stress by an increase in the concentration of antioxidant enzymes and sustain membrane integrity which leads to restoring the damage caused by tBHP. Bacoside A can able to inhibit the progression of Experimental Autoimmune Encephalomyelitis (EAE) may be by the inhibition of inflammatory cytokines and chemokine evolved during active EAE. Bacoside A also has vasorelaxation.

PDMP is a ceramide analog first prepared in a search for inhibitors of glucosylceramide synthase. PDMP has two adjacent chiral centers (C1 and C2) allowing for the formation of four possible isomers. PDMP contains all four of these stereoisomers. PDMP inhibits glucosylceramide synthase by 90% when used at a concentration of 0.8 μM in MDCK cell homogenates, however, the ability to inhibit glucosylceramide synthase has been found to reside in the D-threo (1R,2R) enantiomer. The D-threo PDMP enantiomer is also responsible for inhibition of β-1,4-galactosyltransferase 6 and prevention of lactosylceramide synthesis, which is a promotor of neuroinflammation in mice during chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. PDMP enhances curcumin-induced inhibition of proliferation, JNK activation, and Akt inhibition, as well as induction of apoptosis in WM-115 melanoma cells in vitro.

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM). BIO5192 hydrate selectively binds to α4β1 (IC50=1.8 nM) over a range of other integrins. BIO5192 hydrate results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2]. The combination of BIO5192 hydrate (1 mg kg; i.v.) and Plerixafor (5 mg kg; s.c.) exert an additive effect on progenitor mobilization[1].BIO5192 hydrate (30 mg kg; s.c; bid; during days 5 through 14) delays paralysis associated with EAE (experimental autoimmune encephalomyelitis)[2].BIO5192 hydrate (1 mg kg, i.v.) shows the terminal half-life is 1.1 hours. BIO5192 hydrate (3, 10, and 30 mg kg; s.c.) shows half-lives of 1.7, 2.7, and 4.7 hours, respectively. The blood plasma curves show that the AUC for the s.c. route of administration increased about 2.5-fold from 5,460 h*ng ml for the 3 mg kg dose to 14,175 h*ng ml for the 30 mg kg[1]. Animal Model: C57BL 6J x 129Sv J F1 mice[1] [1]. Ramirez P, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114(7):1340‐1343. [2]. Leone DR, et al. An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2003;305(3):1150-1162.

Isogarcinol is a natural polyisoprenylated benzophenone first isolated from plant species in the genus Garcinia. It has immunosuppressant actions, inhibiting the protein phosphatase calcineurin (IC50 = 36 μM) and suppressing the proliferation of T cells. Oral administration of isogarcinol in mice decreases delayed type hypersensitivity, prolongs graft survival in allogeneic skin transplants, suppresses inflammation in collagen-induced arthritis, and reduces clinical symptoms in experimental autoimmune encephalomyelitis. Isogarcinol inhibits the proliferation of HL-60 and PC-3 cancer cells (IC50s = 4 and 8 μg ml, respectively) through cell cycle arrest and apoptosis.

JC-171 is a selective NLRP3 inflammasome inhibitor, with an IC50 of 8.45 μM for inhibiting LPS ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages[1]. JC-171 (0-100 μM) blocks NLRP3 inflammasome activation and IL-1β production in primary macrophages dose dependently[1]. Cell Viability Assay[1] Cell Line: J774A.1 murine macrophage cells JC-171 treatment delays the progression and reduces the severity of experimental autoimmune encephalomyelitis (EAE) in mouse[1]. Animal Model: Mice immunized subcutaneously with 200 μg Myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide emulsified in Complete Freund's Adjuvant (CFA) on day 0 followed by injection of 200 ng of pertussis toxin. [1]. Chunqing Guo, et al. Development and Characterization of a Hydroxyl-Sulfonamide Analogue, 5-Chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a Novel NLRP3 Inflammasome Inhibitor for Potential Treatment of Multiple Sclerosis. ACS Chem Neurosci. 2017 Oct 18;8(10):2194-2201.

MOG (35-55), human, a constituent of central nervous system myelin, is distinguishable from mMOG (35-55) due to a proline-to-serine substitution at position 42. It possesses immunogenic properties and is partially cross-reactive with mMOG35–55. However, MOG (35-55), human does not induce encephalitogenic effects, and only elicits minimal clinical signs of EAE (experimental autoimmune encephalomyelitis) in comparison to the rodent peptide.

ASP-4058 hydrochloride 是一种选择性的、口服具有活力的的鞘氨醇磷酸受体 1 和 5 (S1P1and S1P5) 的二代激动剂。ASP-4058 hydrochloride 安全性良好，能够改善小鼠实验性自身免疫性脑脊髓炎。

SR12418 是一种特异性的 REV-ERB 合成配体，能够作用于 REV-ERBα (IC50: 68 nM) 和 REV-ERBβ (IC50: 119 nM)，可用于研究实验性自身免疫性脑脊髓炎 (EAE) 和结肠炎。