| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
| 靶点 |
Myeloperoxidase (MPO) inhibitor verdiperstat (AZD3241), with an IC50 of 630 nM, is employed in the investigation of neurodegenerative brain illnesses [1]. Myeloperoxidase is specifically and irreversibly inhibited by verdiperstat (AZD3241), which may also play a role in lowering oxidative stress and consequently chronic neuroinflammation [2].
|
|---|---|
| 体外研究 (In Vitro) |
髓过氧化物酶 (MPO) 抑制剂 verdiperstat (AZD3241) 的 IC50 为 630 nM，用于研究神经退行性脑部疾病 [1]。 verdiperstat (AZD3241) 特异性且不可逆地抑制髓过氧化物酶，这也可能在降低氧化应激和慢性神经炎症方面发挥作用 [2]。
|
| 体内研究 (In Vivo) |
在食蟹猴中静脉注射碳-11标记的 Verdiperstat ([11C]AZD3241) 微剂量后，脑部迅速出现放射性信号。该化合物向脑部的分布非常快，在注射后1.5分钟内观察到最大浓度 (Cmax)，相当于注射放射性的1.9%至2.6%。放射性在脑内均匀分布，随后快速洗脱。该研究证实了 Verdiperstat (AZD3241) 在非人灵长类动物中具有足够的脑部暴露。[1]
|
| 酶活实验 |
测定得到 Verdiperstat (AZD3241) 抑制人髓过氧化物酶 (MPO) 的IC50值为630 nmol/L。该测定基于MPO的生理酶活性。[1]
|
| 动物实验 |
A PET microdosing study was performed in three cynomolgus monkeys (1 female, 2 males) to assess the brain exposure of Verdiperstat (AZD3241). Carbon-11 labeled [11C]AZD3241 was synthesized via a multi-step radiochemical procedure. The formulated product for injection was prepared by dissolving the purified [11C]AZD3241 in phosphate-buffered saline (PBS) containing a small volume of ethanol, followed by sterile filtration. Animals were anesthetized and their heads immobilized. A single intravenous bolus injection of [11C]AZD3241 (injected radioactivity: 160 ± 1 MBq, mean ± SD) was administered over 5 seconds via a sural vein, simultaneously with the start of PET data acquisition. Brain radioactivity was measured continuously for 125 minutes using a high-resolution research tomography (HRRT) PET system. No carrier (unlabeled) drug was co-administered; this was a tracer microdose study. [1]
|
| 药代性质 (ADME/PK) |
In cynomolgus monkeys, following a single intravenous microdose of [11C]AZD3241, the compound rapidly entered the brain. The time to maximum brain concentration (Tmax) was 1.2 to 1.5 minutes. The maximum brain concentration (Cmax) ranged from 1.86% to 2.58% of the injected dose (%ID). The brain distribution was homogeneous, and radioactivity washed out rapidly from the brain. Specific pharmacokinetic parameters such as half-life, clearance, volume of distribution, oral bioavailability, metabolism, and excretion were not reported in this microdosing PET study. [1]
|
| 毒性/毒理 (Toxicokinetics/TK) |
In the described PET microdosing study in cynomolgus monkeys, where only a tracer (micro) dose of [11C]AZD3241 was administered, no adverse effects related to the administration were observed. There were no significant changes in physiological parameters (ECG, heart rate, blood pressure, respiratory rate, oxygen saturation) or blood parameters monitored during the experiment. Toxicity data such as LD50, organ toxicity, or protein binding were not provided. [1]
|
| 参考文献 |
|
| 其他信息 |
Verdiperstat has been used in trials studying the basic science and treatment of Multiple System Atrophy (MSA).
Drug Indication Treatment of amyotrophic lateral sclerosis Treatment of multiple system atrophy Verdiperstat (AZD3241) is a pyrrolo[3,2-d]pyrimidin-4-one derivative developed as a potent and selective inhibitor of myeloperoxidase (MPO). It has been selected as a candidate drug for development to delay progression in patients with neurodegenerative brain disorders. This study developed a rapid four-step carbon-11 radiolabeling method for AZD3241 to enable PET microdosing. The successful synthesis and subsequent PET study in monkeys demonstrated that AZD3241 rapidly crosses the intact blood-brain barrier and achieves homogeneous brain distribution. This confirmed adequate brain exposure, supporting its translation into Phase 2a clinical studies in patients. The homogeneous distribution and rapid washout in the normal monkey brain suggest low non-specific binding in areas with low MPO expression. [1] |
| 分子式 |
C11H15N3O2S
|
|---|---|
| 分子量 |
253.320700883865
|
| 精确质量 |
253.088
|
| CAS号 |
890655-80-8
|
| PubChem CID |
11528958
|
| 外观&性状 |
White to light brown solid powder
|
| LogP |
1
|
| tPSA |
89.4
|
| 氢键供体(HBD)数目 |
2
|
| 氢键受体(HBA)数目 |
3
|
| 可旋转键数目(RBC) |
4
|
| 重原子数目 |
17
|
| 分子复杂度/Complexity |
322
|
| 定义原子立体中心数目 |
0
|
| SMILES |
C1N([H])C2C(N([H])C(=S)N(CCOC(C)C)C=2C=1)=O
|
| InChi Key |
FVJCUZCRPIMVLB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C11H15N3O2S/c1-7(2)16-6-5-14-8-3-4-12-9(8)10(15)13-11(14)17/h3-4,7,12H,5-6H2,1-2H3,(H,13,15,17)
|
| 化学名 |
1-[2-(propan-2-yloxy)ethyl]-2-sulfanylidene-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one
|
| 别名 |
AZD3241; AZD 3241; AZD-3241
|
| HS Tariff Code |
2934.99.9001
|
| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 溶解度 (体外实验) |
DMSO : ~125 mg/mL (~493.45 mM)
|
|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (9.87 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.5 mg/mL (9.87 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.5 mg/mL (9.87 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9476 mL | 19.7379 mL | 39.4758 mL | |
| 5 mM | 0.7895 mL | 3.9476 mL | 7.8952 mL | |
| 10 mM | 0.3948 mL | 1.9738 mL | 3.9476 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
RSL3
ML-210 (CID-49766530)
InvivoChem的所有产品仅用于作科学研究，不面向患者销售
Copyright 2020 InvivoChem LLC | All Rights Reserved 粤ICP备20063088号-1
COA
粤公网安备 44011102003439号
463611831
