encephalomyelitis

Tolperisone hydrochloride (Muscalm) 是中枢作用肌肉松弛剂，可用于研究神经疾病引起的病理性横纹肌硬化(锥体束损伤、脊髓病、多发性硬化症、脑脊髓炎)、痉挛性麻痹及其他肌肉张力障碍相关的脑病。

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。

3-Methoxycatechol 是一种木质素衍生的可再生化学品，可促进食管发生癌变。1,2-Dihydroxy-3-methoxybenzen 对脑脊髓炎病毒（EMCV）表现出很强的抗病毒活性.

Ketotifen fumarate (HC 20511 fumarate) 是组胺 H1 受体和炎症介质释放的环七噻吩阻滞剂。

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。

Lenaldekar (LDK) 抑制 T 细胞扩增和自身免疫性脑脊髓炎。 Lenaldekar 导致 PI3 激酶 AKT mTOR 通路成员的去磷酸化并延迟有丝分裂晚期的敏感细胞。

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.

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。

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。

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)。

Glatiramer acetate 是髓鞘碱性蛋白的合成类似物和免疫调节剂，可用于多发性硬化症的研究。它能够诱导 T 辅助细胞 2 的特异性抑制细胞迁移到大脑并导致原位旁观者抑制。它能够于 MHC 分子强而杂乱的结合，因此与各种髓鞘抗原竞争，使其呈现给 T 细胞。

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。

γ-Fibrinogen377-395 TFA 是纤维蛋白原衍生抑制肽，具有纤维蛋白原表位特性。该化合物能在体外抑制小胶质细胞激活、阻断纤维蛋白与Mac-1相互作用，并在小鼠体内抑制实验性自身免疫性脑脊髓炎(EAE)。该肽适用于多发性硬化症(MS)及其他血脑屏障损伤和小胶质细胞激活相关的神经炎症疾病研究。

BIO-8169 是一种对白细胞介素受体相关激酶 4 (IRAK4) 有高度选择性的抑制剂，IC50为 0.23 nM。它在小鼠模型中显示出优良的药代动力学特征，有效减少促炎细胞因子的产生，并减轻自身免疫性脑脊髓炎 (EAE) 的症状。此外，BIO-8169 具有较好的血脑屏障渗透性，大鼠 Kpu,u 为 0.7。

[Leu144,Arg147]-PLP (139-151) 是髓鞘蛋白脂蛋白 (PLP) 的一种变体肽段，其中在第144位和第147位的色氨酸和组氨酸被亮氨酸和精氨酸所替换。该肽段还充当脑脊髓炎Th1克隆的T细胞受体 (TCR) 拮抗剂，并可在体外阻断T细胞的激活。此外，[Leu144,Arg147]-PLP (139-151) 也有助于抑制实验性自身免疫性脑脊髓炎 (EAE) 的进展。

S1PL-IN-31是一种鞘氨醇-1-磷酸(S1P)裂解酶的抑制剂(IC50 = 210 nM)，同时也是Smoothened(Smo)受体的对抗剂(IC50 = 440 nM)。在体内，S1PL-IN-31 (每天2 mg/kg)能够防止实验性自身免疫性脑炎(EAE)模型大鼠中，由髓鞘少突胶质细胞糖蛋白(MOG)肽段MOG29-152诱发的颈部及胸部淋巴细胞渗透和神经肌肉虚弱。该化合物降低了大鼠的淋巴细胞总数及CD4+ T细胞、CD8+ T细胞和B细胞的水平。S1PL-IN-31 (每天3及10 mg/kg剂量)在雄性和雌性大鼠心脏和淋巴结中增加了S1P水平，并且在雌性大鼠中降低了心率。

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.

Forphenicine is a bacterial metabolite that has been found in S. fulvoviridis and an inhibitor of alkaline phosphatase (IC50 = 0.036 µg/ml for the chicken intestine enzyme). It inhibits the growth of HL-60 leukemia cells when used at a concentration of 10 µM. Forphenicine (50 and 500 µg/animal) increases survival in a guinea pig model of experimental autoimmune encephalomyelitis (EAE).

MOG peptide (35-55) 是一段特定的髓鞘少突胶质细胞糖蛋白 (MOG) 免疫原肽的35至55氨基酸序列。该肽段具有针对CD4+T细胞的特异性活性，并可用于诱导实验性自身免疫性脑脊髓炎 (EAE) 的动物模型。

MOG (92–106), mouse, rat 是一种来自小鼠 大鼠髓磷脂少突胶质细胞糖蛋白的生物活性肽，包含氨基酸片段92至106。在MOG (92–106) 诱导的实验性自身免疫性脑脊髓炎模型中，小鼠会对次级髓磷脂抗原呈现出广泛的B细胞反应性，尽管T细胞反应较弱。该肽段在SJL小鼠、DA大鼠以及恒河猴中均可诱导严重的脑炎。

Experimental allergic encephalitogenic peptide (human) 为EAE多肽类化合物，能够诱导豚鼠发生脑脊髓炎。

Spermidine-d6 is intended for use as an internal standard for the quantification of spermidine by GC- or LC-MS. Spermidine is an endogenous polyamine. It is formed from putrescine by spermidine synthase. Spermidine (25 µM) inhibits the activity of the human inward-rectifying potassium channel Kir2.3 in a patch-clamp assay. It induces autophagy in HeLa cells when used at a concentration of 100 µM and increases the lifespan of D. melanogaster, yeast, and C. elegans. Spermidine (30 mM in the drinking water) reduces demyelination of the optic nerve and disease severity in a mouse model of experimental autoimmune encephalomyelitis (EAE). It reduces increases in blood pressure, left ventricular posterior wall thickness, and heart weight in salt-sensitive Dahl rats fed a high-salt diet, a model of hypertension-induced congestive heart failure.4 Formulations containing spermidine have been used as dietary supplements.

PLP (190-209) 是一种来源于髓磷脂蛋白 (PLP) 的肽段。该化合物广泛应用于实验性自身免疫性脑脊髓炎 (EAE) 动物模型中，以便于开展多发性硬化症的相关研究。

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。

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.

Ketotifen (HC 20-511)为第二代口服活性非竞争性组胺1(H1)受体阻滞剂兼肥大细胞稳定剂，能体外阻断6-磷酸葡萄糖酸脱氢酶(6-PGD)。其对SARS-CoV-2及流感病毒(Influenza virus)展现出抗病毒活性，适用于自身免疫性脑脊髓炎(EAE)与哮喘发作预防研究。

Palmitoylcholine is an acyl choline.1It inhibits protein kinase C activity when used at a concentration of 100 μM.2Palmitoylcholine induces hemolysis in rat erythrocytes.3Plasma levels of palmitoylcholine are decreased in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).1 1.Germain, A., Barupal, D.K., Levine, S.M., et al.Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl lipids and steroidsMetabolites10(1)34(2020) 2.Nakadate, T., and Blumberg, P.M.Modulation by palmitoylcarnitine of protein kinase C activationCancer Res.47(24 Pt 1)6537-6542(1987) 3.Cho, K.S., and Proulx, P.Interactions of acyl carnitines and other lysins with erythrocytes and reconstituted erythrocyte lipoproteinsBiochim. Biophys. Acta318(1)50-60(1973)

MBP Ac1-9 是髓鞘碱性蛋白(MBP)的一个特定肽段，主要应用于实验性自身免疫性脑脊髓炎(EAE)模型研究中。此肽段是一个免疫优势表位，可以诱导T细胞的免疫应答，并导致与多发性硬化症相似的病理改变。研究者利用MBP Ac1-9探究T细胞的激活机制及自身免疫反应。

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。

J5 peptide是MBP抑制剂，竞争性阻断MBP85-99与HLA-DR2的结合。该肽段能减轻PLP139-151/MBP85-99诱导的小鼠实验性自身免疫性脑脊髓炎(EAE)。J5 peptide主要用于研究炎症和免疫疾病。

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.

PF-04957325 是 PDE8 的抑制剂，具有高效性和选择性。PF-04957325 对 PDE8A的IC50为 0.7 nM ，对 PDE8B 的 IC50 为 0.3 nM。PF-04957325 可用于研究自身免疫性脑脊髓炎。

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。

D-Mannuronic acid sodium，一种可从Macrocystis pyrifera中分离得到的化合物，显示出在自身免疫性脑脊髓炎(EAE)、佐剂性关节炎(AIA)、肾病综合征以及急性肾小球肾炎的研究中具有潜在应用价值。

Tridocosahexaenoylglycerol (TG-DHA)是一种改善小鼠自身免疫性脑脊髓炎的口服有效膳食补充剂，展现出对神经退行性疾病的有益作用，并能改善糖尿病视网膜病变黄斑功能。该化合物在神经系统性疾病、炎症免疫疾病以及代谢性疾病研究中具有应用潜力。

KSI-6666作为一种口服有效的竞争性鞘氨醇1-磷酸受体1 (S1PR1) 拮抗剂，其IC50值仅为6.4 nM。在自身免疫性脑脊髓炎模型及T细胞转移性结肠炎模型中，KSI-6666展示了显著的抗炎效果。

γ-Fibrinogen377-395是一种衍自纤维蛋白原的抑制性肽段，也被认为是纤维蛋白原的表位之一。它能在体外抑制小胶质细胞的激活并阻断纤维蛋白与Mac-1的交互作用；此外，在小鼠体内能够抑制实验性自身免疫性脑脊髓炎(EAE)的发展。因此，γ-Fibrinogen377-395对于多发性硬化症(MS)以及其他与血脑屏障损伤和小胶质细胞活化相关的神经炎症性疾病的研究具有潜在的应用价值。

Myelin Basic Protein (1-11) 是髓鞘碱性蛋白 (MBP) 的一个致脑炎表位，并且常用于诱导实验性自身免疫性脑脊髓炎 (EAE)。

6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels.

Potent and selective KV1.3 channel blocker (IC50 values are 0.0019 and 0.65 nM for KV1.3 and KV1.1, respectively). Inhibits CD4+ CCR7- T cell activation. Ameliorates rat experimental autoimmune encephalomyelitis, in a model for multiple sclerosis.

24, 25-Dihydroxy VD2 (24,25-Dihydroxy vitamin D2) 是维生素 D2 的 代谢产物，是维生素 D在体内存在25 羟维生素 D 的异构体。

R 715是一种布拉迪肾上腺素B1受体拮抗剂。它抑制在表达布拉迪肾上腺素B1受体的孤立人类脐带中由布拉迪肾上腺素引发的收缩（pA2 = 8.49）。R 715（200、400及600 µg/kg）通过尾部闪烁测试减少了由链脲佐菌素（STZ）诱导的糖尿病神经病变小鼠模型中尾部撤回的潜伏期。它还在以髓磷脂少突胶质细胞糖蛋白（MOG）（35-55）（MOG35-55）抗原肽诱导的实验性自体免疫性脑炎（EAE）小鼠模型中，通过每天1 mg/kg的剂量减少了后肢无力和瘫痪的发病率，改善对称步态，并减少脊髓炎症灶点数、神经元脱髓鞘以及病灶单核细胞侵袭。R 715（0.01 nmol/动物，脑室内）能在自发性高血压大鼠中降低平均动脉血压并增加心率。

[Leu144,Arg147]-PLP (139-151)是髓鞘脂蛋白(PLP)的一种突变肽段，包含位于144和147位置的色氨酸到亮氨酸以及组氨酸到精氨酸的替换。使用[Leu144, Arg147]-PLP (139-151)（50 µg）乳化于完全弗氏佐剂(CFA)免疫后，能增加小鼠脾脏中的IL-4水平。它在体外抑制Th1细胞激活，但在体内不抑制，其中它诱导调节性T细胞的产生。用[Leu144, Arg147]-PLP (139-151)预免疫可以延迟由脑炎肽PLP (178-191)、髓磷脂少突细胞蛋白(MOG) (92-106)或髓鞘基础蛋白(MBP)在小鼠中诱导的实验性自身免疫性脑炎(EAE)的发病。

D359-0396 是一种口服活性的 NLRP3 炎性体抑制剂，能有效抑制巨噬细胞焦亡（pyroptosis）以及 IL-1β 的释放，并阻止 NLRP3 和 ASC 的寡聚化，抑制 GSDMD 的裂解。该化合物在动物模型中能减轻小鼠的 EAE 症状，并提高感染性休克后的小鼠存活率。

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.

AKP-11 is a sphingosine-1-phosphate receptor 1 (S1P1) agonist with an EC50 of 0.047 μM for [35S]GTPγS binding to CHO-K1 cell membranes expressing human S1P1. It reduces S1P1 surface expression and enhances Akt and ERK phosphorylation in CHO cells with S1P1-HA at a 100 nM concentration. At doses of 1.3 and 3 mg/kg, AKP-11 lowers IFN-γ and IL-17 protein levels in the spinal cord and mitigates disease severity in a rat experimental autoimmune encephalomyelitis (EAE) model. Additionally, it decreases peripheral total lymphocyte and specific T cell subsets (CD4+, CD8+, and CD26L+ T cells) counts in both EAE rats and healthy controls at a 1.3 mg/kg dosage.

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.