pathology

PLX5622 是一种口服小分子 CSF1R 抑制剂，能够选择性耗竭小鼠和大鼠的大脑微胶质细胞，常用于构建微胶质细胞相关的神经炎症、神经退行性疾病（如阿尔茨海默病、帕金森病）、脑损伤及脑免疫调节模型。

Selisistat (EX-527) 是一种去乙酰化酶 SIRT1 的抑制剂 (IC50=38 nM)，具有有效性和特异性。Selisistat 可以用于神经系统疾病如亨廷顿舞蹈病的研究。

PD146176 (NSC-168807) 是一种 15-脂氧合酶(15-LO)抑制剂，抑制兔网织红细胞 15-LO，Ki 为 197 nM，IC50 为 0.54 μM。 它通过刺激老年三重转基因小鼠的自噬来逆转认知障碍、脑淀粉样变性和 tau 病理学。

CA77.1 是一种新型伴侣介导的自噬激活剂，用于治疗阿尔茨海默病。它是 AR7 的衍生物，可以增加溶酶体受体在溶酶体中的表达。

D-GsMTx4 TFA 是一种具有选择性的蜘蛛毒液肽，是一种TRPC1 / 6和Piezo2抑制剂，可抑制属于 Piezo 和 TRP 通道家族的阳离子可渗透的机械敏感性通道 （MSCs），阻断阳离子选择性的拉伸激活通道 （SAC），减弱溶血磷脂酰胆碱 （LPC） 诱导的星形胶质细胞毒性和小胶质细胞反应性。D-GsMTx4 TFA 在小鼠缺血/再灌注模型中预防心肌梗死，可用于鉴定兴奋性 MSC 在正常生理学和病理学中的作用。

alphaSYN-IN-NAB2 是一种神经元保护剂，是一种由 NAB2基因编码的蛋白质。NAB2 高效且具有选择性地保护多种细胞免受 α-syn 毒性。NAB2 对依赖于 E3 泛素连接酶 Rsp5/Nedd4 的内体转运具有促进作用。NAB2 确定 α-syn 生物学中的一个可活性分子节点，该节点可以纠正其潜在病理学的多个方面，包括功能失调的内体和内质网到高尔基体囊泡的运输。NAB2参与细胞分化、凋亡和应激反应等细胞过程，可用来研究癌症、神经发育和神经元活动。

N-Ethyl-o-toluidine是一种具有遗传毒性和抗癌潜力的药物，对特定基因改变的酵母菌株具有＞70%的生长抑制作用，还可以作为合成染料的中间体。

ATN-161 acetate 是一由纤连蛋白的协同区域衍生出的五肽化合物，是一种非竞争性整合素-α5 拮抗剂，具有抗肿瘤活性，可减轻 caerulein 诱导的急性胰腺炎的病理状况。 ATN-161 acetate 通过减少整合素 α5、MMP-9 和纤连蛋白表达抑制 OGD/R 诱导的细胞外基质 （ECM） 沉积。

PLX5622 hemifumarate 是一种高度选择性、能透过血脑屏障且具有口服活性的 CSF1R 抑制剂，IC50 值为 0.016 μM，Ki 值为 5.9 nM，可用于病程发展前和过程中对扩增且特异性的小胶质细胞进行消除，可用于诱导阿尔茨海默症模型。

Glutathione monoethyl ester 是谷胱甘肽的衍生物，可以保护运动神经元细胞 NSC-34 免受突变导致的 TDP-43 病理损害的影响。这些损害包括聚集体的减少、核清除、活性氧 (Reactive Oxygen Species) 产生以及细胞死亡的降低。

Antibacterialagent 266 (Compound C5) 是一种有效的植物病原菌抑制剂，通过破坏细菌细胞膜的完整性而起作用，对Xanthomonasoryzaepvoryzae (Xoo) 和X. axonopodispvcitri (Xac) 的EC50值分别为24.1 μg/mL和39.0 μg/mL。Antibacterialagent 266 可用于植物病理学研究以及农业抗菌制剂的开发。

BF-170是一种选择性的tau纤维结合剂，其EC50为221 nM。BF-170具有优越的血脑屏障穿透性，在小鼠静脉注射后2分钟脑组织中的浓度达到9.1% ID/g（在30分钟后，脑内清除率为0.25% ID/g），可作为阿尔茨海默病(AD)中tau蛋白病理成像的探针。在阿尔茨海默病早期阶段研究中，BF-170具有关键作用，并有潜力用于tau相关神经退行性疾病的成像研究。

VEN-02XX 是一种具备口服活性且可穿透脑组织的 NLRP3 抑制剂。它能够抑制 IL-1β 和 IL-18 的释放，IC50 分别为 0.3 和 0.28 μM。在 5XFAD/Rubicon KO 小鼠模型中，VEN-02XX 可改善小鼠的记忆和认知功能，抑制微胶质细胞增生，并减轻神经炎症和 tau 蛋白病理。VEN-02XX 适用于阿尔茨海默症 (AD) 的研究。

MRL828结合了Tau病理结合配体和基于ATTEC技术修饰的鸟嘌呤基团，能够通过自噬-溶酶体途径 (ALP) 选择性标记聚集的tau蛋白以清除。MRL828可减少细胞内Tau聚集体并促进Tau的分泌。

20-SOLA 是首个具有口服活性的水溶性 20-HETE 拮抗剂。它显著改善了链脲佐菌素（STZ）糖尿病小鼠模型的血压变化和肾损伤。此外，20-SOLA 作为 GPR75 受体阻滞剂，有助于心血管病理学研究。

IDT is an orally active TNFα modulator. It acts by altering neutrophil infiltration, improving cognition and diminishing tau and amyloid pathology in the 3xTgAD mouse model.

SR1555 is a selective RORγ inverse agonist that inhibits the development and function of TH17 cells, a subset of T cells that have been involved in the pathology of several autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

BNC-1 is a modulator of amyloid pathology. BNC-1 significantly decreases amyloid burden and improves markers of synaptic integrity in well-established mouse models of amyloid deposition by promoting phosphorylation and activation of Elk-1.

BF 126 has potential applications in vivo imaging of tau pathology in Alzheimer's disease

Sulfatides are endogenous sulfoglycolipids with various biological activities in the central and peripheral nervous systems, pancreas, and immune system. They are produced from the combination of ceramide and UDP-galactose in the endoplasmic reticulum followed by sulfation in the Golgi apparatus. The ceramide portion contains variable fatty acid chain lengths, which are tissue- and pathology-dependent. Sulfatides are primarily found in the myelin sheath of oligodendrocytes and Schwann cells, with smaller chain lengths predominant during development and longer chain lengths predominant in mature cells. They accumulate in the lysosome of patients with metachromatic leukodystrophy, a disorder characterized by arylsulfatase A deficiency. Sulfatides are also located in pancreatic β-cells and inhibit insulin release from isolated rat pancreatic islet cells, suggesting a potential role in diabetes. Sulfatides can induce inflammation in glia in vitro and certain sulfatides, such as C24:1 3'-sulfo-galactosylceramide, can induce an immune response in vitro in mouse splenocytes. Sulfatides (bovine) (sodium salt) is a mixture of isolated bovine sulfatides.

MBX-8025 is an agonist of peroxisome proliferator-activated receptor δ (PPARδ).1 It is greater than 750- and 2,500-fold selective for PPARδ over PPARα and PPARγ. MBX-8025 (10 mg/kg per day for eight weeks) reduces increases in fasting blood glucose and serum insulin levels, and decreases insulin resistance in Alms1 mutant (foz/foz) mice fed an atherogenic diet as a model of diet-induced obesity, type 2 diabetes, and non-alcoholic steatohepatitis (NASH).2 It also decreases serum alanine transaminase (ALT), as well as serum and hepatic cholesterol and triglyceride, levels and reduces markers of NASH in the same model. |1. Bays, H.E., Schwartz, S., Littlejohn, T., 3rd, et al. MBX-8025, a novel peroxisome proliferator receptor-δ agonist: Lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J. Clin. Endocrinol. Metab. 96(9), 2889-2897 (2011).|2. Haczeyni, F., Wang, H., Barn, V., et al. The selective peroxisome proliferator-activated receptor-delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol. Commun. 1(7), 663-674 (2017).

PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)

Advanced glycation end products (AGEs) are compounds formed by non-enzymatic chemical reactions following the bonding of sugars to proteins or lipids during diabetes, uremia, aging, rheumatic arthritis, and other conditions. A receptor for the AGEs (RAGE) binds certain members of this class to initiate cell signaling.[1][2] Pentosidine is a well-characterized natural AGE that is often used as a biomarker for the production of all AGEs. While pentosidine can be measured in urine, the majority of this AGE is catabolized before excretion.[3] Reference：[1]. Neeper, M., Schmidt, A.M., Brett, J., et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. The Journal of Biological Chemisty 267(21), 14998-15004 (1992).[2]. Brett, J., Schmidt, A.M., Yan, S.D., et al. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. American Journal of Pathology 143(6), 1699-1712 (1993).[3]. Miyata, T., Ueda, Y., Horie, K., et al. Renal catabolism of advanced glycation end products: The fate of pentosidine. Kidney International 53, 416-422 (1998).

Q134R, a neuroprotective hydroxyquinoline derivative that suppresses nuclear factor of activated T cell (NFAT) signaling. Q134R can across blood-brain barrier. Q134R has the potential for Alzheimer’s disease (AD) and aging-related disorders research[1]. Q134R (1-10 μM) suppresses NFAT signaling, without inhibiting calcineurin activity. Q134R partially inhibits NFAT activity in primary rat astrocytes, but does not prevent calcineurin-mediated dephosphorylation of a non-NFAT target, either in vivo, or in vitro[1]. Q134R (4 mg/kg; orally gavage; twice per day; for 7 days) treatment improves cognitive function in rodent models of AD‐like pathology[1]. [1]. Pradoldej Sompol, et al. Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology. Aging Cell. 2021 Jul;20(7):e13416.