| Bioactivity | H3R antagonist 4 (compound 11L) was a dual inhibitor of cholinesterase and histamine receptor (H3R), with corresponding IC50 of 7.04 μM (eeAChE), 9.73 μM (hAChE)(reversible) and 1.09 nM (H3R) , respectively. H3R antagonist 4 inhibited the aggregation of Aβ1-42 induced by itself and Cu2+ (95.48% and 88.63%) , and degraded the Aβ1-42 fibrils induced by itself and Cu2+ (80.16% and 89.30%) . H3R antagonist 4 chelate biometals such as Cu2+, Zn2+, Al3+, and Fe2+. H3R antagonist 4 significantly reduced tau protein hyperphosphorylation induced by Aβ1-42 and inhibited RSL-3-induced apoptosis and ferroptosis in PC12 cells. H3R antagonist 4 had the best blood-brain barrier permeability and intestinal absorption in hCMEC/D3 and hPepT1-MDCK cells.H3R antagonist 4 ameliorates learning and memory impairment in a mouse model of Alzheimer's disease induced by scopolamine (HY-N0296) [1] . |
| Invitro | H3R antagonist 4（compound 11l）对eeAChE，eqBuChE 和 hAChE 有抑制作用，对应的 IC50 分别为 7.04 μM，13.40 μM 和 9.73 μM 且对 huAChE 抑制机制是可逆的[1] 。H3R antagonist 4 与 AChE 结合，占据酶促CAS、midgorge位点和PAS。与 huAChE 的阴离子活性中心和外周阴离子位点相互作用，可同时结合 CAS和 PAS 位点作为双位点 AChE 抑制剂[1] 。H3R antagonist 4 对自身和 Cu2+ 诱导的 Aβ1-42 聚集有良好的抑制作用 (95.48%和88.63%) (ThT fluorescence assay)，和对自身和 Cu2+ 诱导的 Aβ1-42 原纤维具有良好的降解作用 (80.16%和89.30%)(TEM)[1]。 H3R antagonist 4 (TRFRET) 抑制 H3R 的 IC50 为 1.09 nM[1]。H3R antagonist 4 (5 µM，10 µM 和 20 µM) (WB) 在 PC12 细胞中可抑制异常的 tau 磷酸化[1]。H3R antagonist 4 (11 μM) 提高 PC12 (经 800 μM H2O2) 存活率为 75.66%，降低了 ROS 水平。通过降低 ROS 积累来保护 PC12 细胞免受 H2O2影响，凋亡细胞比例显著增加，达到 22.9%±0.36%[1]。 H3R antagonist 4 (5，10，20 μM) 抑制 RSL3 诱导的 PC12 细胞铁死亡，显著提高了细胞活力。诱导的损伤提高体外血脑屏障通透性[1]。 H3R antagonist 4（UV–vis spectrometry）可螯合 Cu2+、Zn2+、Al3+ 和 Fe2+ 等生物金属[1]。 H3R antagonist 4 在 hPepT1-MDCK 细胞中提高 PepT1 的蛋白表达[1]。H3R antagonist 4 (0 - 80 μM，1h) 在 BV-2 细胞中显示抗炎作用且不影响增殖[1]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. 0 --> H3R antagonist 4 相关抗体: Western Blot Analysis[1] Cell Line: |
| In Vivo | H3R antagonist 4 (compound 11l) (2.5和5.0 mg/kg) 能有效改善东莨菪碱（HY-N0296）诱导的神经细胞病理形态学改变，可显著改善AD模型小鼠的认知缺陷和空间记忆[1]。 H3R antagonist 4(compound 11l) pharmacokinetics form[1]H3R antagonist 4 (compound 11l)给药后的药代动力学表格[1]Parameter |
| Formula | C30H36N2O9 |
| Molar Mass | 568.61 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Jiao Chen,et al. Scutellarein derivatives with histamine H3 receptor antagonism and cholinesterase inhibitory potency as multi target-directed ligands for possible Alzheimer's disease therapy. Bioorganic Chemistry. 2024 Aug 8;151:107704. |