alzheimer’s disease

Potent somatostatin receptor 1 (sst1) agonist; displays selectivity for sst1 (IC50 values are 30.9 nM, 345 nM, > 1 μM, > 10 μM and > 10μM for human sst1, sst3, sst4, sst2 and sst5 respectively). Attenuates somatostatin release in the rat nucleus accumbens

CM-675 是磷酸二酯酶 5 (PDE5)和I 类组蛋白去乙酰化酶 (HDAC1) 的选择性抑制剂，对 PDE5 和 HDAC1 的IC50 值分别为114 nM 和673 nM。CM-675 可用于阿尔兹海默症的研究。

MS8511 是一种选择性的G9a GLP 共价的不可逆抑制剂，可靶向底物结合位点的半胱氨酸残基，IC50值为 100 nM ( G9a) 和 140 nM (GLP)，Kd 值44 nM (G9a) 和 46 nM (GLP)。 MS8511 可降低细胞内 H3K9me2 水平并提高抗增殖活性。MS8511 可用于研究多种癌症 (包括脑癌、乳腺癌、卵巢癌、肺癌、膀胱癌、黑色素瘤、结肠直肠癌) 和其他疾病,如阿尔茨海默病 (AD)、镰状细胞病、Prader-Willi 综合征 (PWS).

Colchicine 是一种具有口服活性的天然生物碱，通过抑制微管蛋白聚合（IC50=3 nM）及作为α3甘氨酸受体的竞争性拮抗剂，具有广泛的抗炎、免疫抑制和抗纤维化活性，能抑制NLRP3炎症小体激活预防NSAID引起的小肠损伤，具备用于痛风性关节炎和风湿病研究的潜力，且常用于构建阿尔茨海默症模型。

3-Indolepropionic acid (Indolepropionic acid) 是强效的抗氧化剂，具有研究阿尔兹海默症的潜能。

L-Threonic acid magnesium salt 可增加老年大鼠和晚期阿尔茨海默病 (AD) 模型小鼠的突触密度和记忆能力。

SHIP2-IN-1 是一种 SHIP2 抑制剂，IC50=2 µM。它能够使 GSK3β 的 Ser9 位点磷酸化，抑制 GSK3β 的活化。它可用于研究阿尔滋海默症。

Aβ42-IN-1 free base是一种口服活性的γ-secretase调节剂，具有高暴露度。该化合物能显著降低小鼠脑中Aβ42的水平，IC50为0.091 μM，显示出在阿尔茨海默病研究中的潜力。

BuChE-IN-TM-10 (TM-10) 是一种有效的丁基胆碱酯酶 (BuChE) 抑制剂，其IC50 值为8.9 nM。BuChE inhibitor 1能够抑制和分解自诱导的Aβ聚合, 表现出强大的抗氧化活性和良好的血脑屏障 (BBB) 渗透性。可用于阿尔兹海默症的研究。

GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT), which could be useful for the prophylaxis or treatment of diabetes, hyperlipidemia, non-alcoholic fatty liver, Alzheimer’s disease, Parkinson’s disease, cerebrovascular dementia, cerebral infa

β-Amyloid (25-35) 是阿尔茨海默氏淀粉样蛋白β肽的 Aβ(25-35) 片段，具有神经毒性作用，常用于构建阿尔茨海默症细胞和动物模型。

Okadaic acid 是一种强效的聚醚海洋毒素，主要积聚于海洋软体动物的消化腺中。它是一种高效且选择性的蛋白质磷酸酶（PP）抑制剂。Okadaic acid 通过抑制这些蛋白磷酸酶增加了多种蛋白的磷酸化水平，具有肿瘤启动子的作用，并能诱导tau蛋白的磷酸化,可用于构建阿尔兹海默症和皮肤癌模型。

ROS151, 作为一种AChE抑制剂, 在不同条件下表现出不同的抑制活性，其IC50值分别为14 nM (hAChE)、1.68 μM (eqBChE)、8.17 μM (hFAAH)。此外，它还能有效螯合Fe3+和Cu2+。因此，ROS151可被应用于阿尔茨海默病的相关研究。

AChE-IN-79 (compound 3i)，作为一种AChE抑制剂，表现出对AChE的显著抑制作用，其IC50值为2.7 µM，主要用于阿尔茨海默病的相关研究。

Imidazole-d4是一种同位素标记的Imidazole，属于杂环芳香族化合物。咪唑类分子被广泛应用于缓蚀剂以及酶抑制剂，如乙酰胆碱酯酶（AChEI）和黄嘌呤氧化酶（XO），并展示出抗真菌、抗结核、抗炎、抗氧化和镇痛等生物活性。此类化合物能够阻止血小板微粒体将内过氧化物(PGG2 和 PGH2)转化为血栓素A2。咪唑衍生物对SARS-CoV-2 3ClPro酶的抑制作用表明其在阿尔茨海默病、痛风、新冠肺炎和血栓疾病等研究中具有潜力。

Casein kinase1δ-IN-26 (compound 505) 是一种高效的casein kinase1δ抑制剂，适用于阿尔茨海默病等神经退行性疾病的研究。

MDAR IN-1 (Compound 5m) 是一种能够穿透大脑的乙酰胆碱酯酶 (AChE) 抑制剂和NMDAR受体GluN1/GluN2B亚型拮抗剂。它有效抑制AchE活性，增强胆碱能神经传递，同时阻断NMDAR以减少兴奋性神经毒性。MDAR IN-1 有潜力被用于阿尔茨海默病的研究。

GSK-3β inhibitor 9 (Compound 9b) 是一种具有高选择性、口服有效的 GSK-3β抑制剂，IC50为 35 nM。GSK-3β inhibitor 9 显示出良好的药代动力学特征，包括良好的血脑屏障渗透。GSK-3β inhibitor 9 可用于阿尔茨海默病的研究。

CM-414 is a dual inhibitor of HDACs and PDE5 for the Treatment of Alzheimer’s Disease (IC50 values of 60 nM, 310 nM, 490 nM, 322 nM, and 91 nM against PDE5, HDAC1, HDAC2, HDAC3, and HDAC6, respectively). Chronic treatment of Tg2576 mice with CM-414 dimini

SCH-900229, a potent presenilin 1 selective γ-secretase inhibitor, used to treat Alzheimer’s Disease.

AZD8926 is a potent and selective inhibitor of GSK3β(glycogen synthase kinase-3β). AZD8926 is potential for treating Alzheimer’s disease (AD), schizophrenia, and chronic as well as acute neurodegenerative diseases.

SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD)[1][2]. SAR502250 (0.01-1 μM; 36 h) attenuates the Aβ25-35-induced cell death in rat embryonic hippocampal neurons[2]. SAR502250 (1-100 mg kg; a single p.o,) attenuates tau hyperphosphorylation in the cortex and spinal cord of transgenic mice expressing P301L tau[2].SAR502250 (10-30 mg kg; p.o. once daily for 7 weeks) improves the cognitive deficit in transgenic APP(SW) Tau(VLW) mice after infusion of Aβ25-35[2].SAR502250 (10-30 mg kg; a single p.o.) significantly increases the percentage of lever-presses in the inter-response time (IRT) bin (49-96 s), with a significant augmentation of the percentage of reinforced responses[2].SAR502250 (30 mg kg; i.p. once daily for 28 d) ameliorates chronic stress-induced degradation of the physical state of the mice coat[2].SAR502250 (10-60 mg kg; a single p.o.) decreases hyperactivity produced by psychostimulantsin mice[2]. [1]. Fukunaga K, et, al. 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7.[2]. Griebel G, et, al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents. Sci Rep. 2019 Dec 2;9(1):18045.

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.

Glycerophosphorylethanolamine is an active phosphodiester metabolite of phosphatidylethanolamine.1,2It promotes aggregation of amyloid-β (1-40) (Aβ40)in vitro, and levels of glycerophosphorylethanolamine are elevated in postmortem brains isolated from patients with Alzheimer’s disease. 1.Klunk, W.E., Xu, C.J., McClure, R.J., et al.Aggregation of β-amyloid peptide is promoted by membrane phospholipid metabolites elevated in Alzheimer’s disease brainJ. Neurochem.69(1)266-272(1997) 2.Blusztajn, J.K., Lopez Gonzalez-Coviella, I., Logue, M., et al.Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer’s disease but not of Down’s syndrome patientsBrain Res.536(1-2)240-244(1990)