aβ42-in-1

Aβ42-IN-1，化合物 1v，是一种新型有效且具有口服活性的 γ 分泌酶调节剂 (GSM)。 Aβ42-IN-1 在不抑制 CYP3A4 的情况下，在培养细胞中有效降低Aβ42水平，IC50值为 0.091 μM。Aβ42-IN-1 显示出良好的药代动力学特征。

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。

Aβ-IN-1 是一种新型有效且具有口服活性的 γ 分泌酶调节剂 (GSM)。 Aβ-IN-1 在不抑制 CYP3A4 的情况下，在培养细胞中有效降低 Aβ42 水平，IC50值为 0.091 μM。Aβ-IN-1 显示出良好的药代动力学特征。

Aβ42-IN-2 是一种 γ-secretase 调节剂。Aβ42-IN-2 对 Αβ42 的 IC50 值为 6.5 nM 。Aβ42-IN-2 可用于阿尔茨海默症相关的研究。

Hematoxylin (Natural Black 1) 是一种天然存在的类黄酮化合物，衍生自木柴树Haematoxylon campechianum。它是一种组织学上的核染色剂，也是一种有效的Aβ42原纤维形成的抑制剂，IC50=1.6 µM。

Licochalcone B 是从Glycyrrhiza inflate 根中提取的。它能够抑制淀粉样蛋白 β 自聚集作用 (IC50=2.16 μM) ，分解预先形成的 Aβ42原纤维，并通过螯合金属离子抑制金属诱导的 Aβ42聚集。

3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) 是 γ-secretase 抑制剂。它导致 Aβ42 和 notch-1 Aβ-like peptide 25 (Nβ25) 的释放水平降低。它是母体血清中 3,3’-diiodothyronine sulfate (T2S) 的交叉反应物质，可作为胎儿甲状腺功能减退的标志物。

Aftin-4 是一种 β-淀粉样蛋白42(Aβ42) 的诱导剂。

BPN-15606 is a highly potent, orally active γ-secretase modulator (GSM), attenuates the production of Aβ42 and Aβ40 by SHSY5Y neuroblastoma cells with IC50 values of 7 nM and 17nM, respectively. BPN-15606 has acceptable PK PD properties, including bioavai

Amyloid-β-IN-1 (compound 13) 为一个人工合成的多肽，包含 Aβ42 的疏水 C 末端区域“VVIA-NH2”及其逆向序列“AIVV-NH2”，具有抑制淀粉样蛋白-β (Aβ) 聚集及抗神经毒性的作用。

Simufilamum（亦称PTI-125）是一种针对改变构型的filamin A的小分子口服化合物候选物。它可以结合并逆转阿尔茨海默症大脑中的支架蛋白filamin A的改变构型，从而减缓阿尔茨海默症的病理发展。此外，PTI-125还能降低tau蛋白的超磷酸化、减少Aβ42的聚集沉积、神经纤维缠结和神经炎症。该化合物在体外实验中显示，对照组和阿尔茨海默病（AD）患者死后的海马切片具有浓度依赖性的效力，起始浓度为1 picomolar（pM）。PTI-125是首个优先结合并逆转蛋白病变改变构型的治疗候选物。

Donecopride is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT4E(Ki= 8.5 nM) and an inhibitor of acetylcholinesterase (AChE; IC50= 16 nM).1It is selective for AChE over butyrylcholinesterase (BChE; IC50= 3,530 nM) but does bind to 5-HT2Band sigma-2 (σ2) receptors (Ki= 1.6 nM for both) in a panel of 42 neurotransmitter receptors and transporters. Donecopride induces release of soluble amyloid precursor protein-α (sAPP-α) in COS-7 cells transiently expressing 5-HT4with an EC50value of 11.3 nM. Oral administration of donecopride (1 mg/kg) reduces brain soluble and insoluble amyloid-β (1-42) levels and increases the time spent exploring the novel object in the novel object recognition (NOR) test in the 5XFAD transgenic mouse model of Alzheimer's disease. Donecopride (3 mg/kg, p.o.) prevents a reduction in spontaneous alternation behavior induced by intracerebroventricular administration of soluble Aβ42 (sAβ42) in the Y-maze in mice.2 1.Lecoutey, C., Hedou, D., Freret, T., et al.Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatmentProc. Natl. Acad. Sci. USA111(36)E3825-E3830(2014) 2.Rochais, C., Lecoutey, C., Hamidouche, K., et al.Donecopride, a Swiss army knife with potential against Alzheimer's diseaseBr. J. Pharmacol.177(9)1988-2005(2020)

Biotin-amyloid-β (1-42) peptide is an affinity probe that allows amyloid-β (1-42) (Aβ42) to be detected or immobilized through interaction with the biotin ligand. It has been used to identify Aβ42 interaction partners in rat hippocampal synaptosomal membranes.

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)

Amyloid-β (1-8, A2V) is a truncated form of amyloid-β (Aβ) that contains a valine to alanine substitution at position 2 of the Aβ numbering convention (Aβ A2V), which corresponds to position 673 of the amyloid precursor protein (APP) numbering convention (APP A673V). An Aβ (1-40) (Aβ40) A2V peptide increases the production of Aβ and the rate and amount of amyloid fibril formation in vitro, effects that can be reduced by coincubation with wild-type Aβ40. Aβ40 and Aβ42 levels are increased in CHO cells expressing the Aβ A2V mutation and in fibroblasts derived from patients with the Aβ A2V mutation. As a homozygous mutation, Aβ A2V is correlated with Alzheimer's disease with distinctive pathological features, but disease does not develop in patients with a heterozygous Aβ A2V mutation.

TAMRA-Amyloid-β (1-42) peptide is a fluorescently labeled peptide. Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-residue protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease. Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers. TAMRA-Amyloid-β (1-42) peptide is a labeled form of Aβ42 containing carboxytetramethyl rhodamine (TAMRA), which displays excitation/emission maxima of 543/572 nm, respectively.

γ-Secretase modulator 12 (Compound 1a) is a selective compound that effectively reduces amyloid-β42 (Aβ42) levels with an IC50 of 0.39 μM. It is specifically designed for Alzheimer's disease research. Notably, γ-Secretase modulator 12 exhibits a favorable brain plasma ratio (Kp, brain = 0.72) in mice [1].

'(Met(O)35)-Amyloid β-Protein (1-42)，Aβ42的一种氧化形态，位于Met35。该化合物可形成与Aβ40具有相似大小和分布特征的寡聚体，适用于阿尔茨海默病（AD）研究。'

(Glu20)-Amyloid β-Protein (1-42) 是一种具有 Glu20 突变的淀粉样蛋白β (Aβ) 变体，该变体的原纤维化速度较慢。此突变能够减少 Aβ 的聚集倾向，进而阻止缓慢原纤化肽的累积。它是阿尔茨海默病中血管及脑内淀粉样沉积物的关键组成部分。

BACE1-IN-13 (Compound 36)为一种BACE1抑制剂，展现出口服活性，IC50为2.9 nM。该化合物在hAβ42细胞中显示出强效 (IC50=1.3 nM)，证实了其心血管安全性，并在小鼠与狗的动物模型中有效降低Aβ42水平。

Z-Phe-Ala-diazomethylketone 直接与 Aβ42 单体及其小型低聚物相结合，能抑制 Aβ42 在溶液中形成的十二聚体以及原纤维的生成，显示出在神经退行性疾病研究中的应用潜力。

Remternetug为一种人源化IgG1-kappa型单克隆抗体，针对APP (Aβ42 N3pGlu)的特定焦谷氨酸形式。该抗体能够特异性识别并结合形成淀粉样斑块的Aβ聚集体。

DDC 3′-O-β-D glucuronide（化合物5）作为一种药物代谢物，具备抑制Aβ42纤维化及其寡聚化的能力，表现出在阿尔茨海默病研究中的应用潜力。

2',3'-Dihydroxy-4',6'-dimethoxychalcone 能够抑制β淀粉样蛋白(Aβ42)的纤维化与聚集，并具有口服活性，在大脑中可进行检测。