规格 | 价格 | 库存 | 数量 |
---|---|---|---|
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
Other Sizes |
|
靶点 |
Mcl-1 (IC50 = 0.7 nM); Mcl-1 (Kd = 0.17 nM)
|
|
---|---|---|
体外研究 (In Vitro) |
AZD5991 是一种有效的直接 Mcl-1 抑制剂,与其他 Bcl-2 家族蛋白相比具有高选择性。 AZD5991 通过直接与 Mcl-1 结合并激活 Bak 依赖性线粒体凋亡途径,在癌细胞中快速触发细胞凋亡,尤其是在骨髓瘤和急性髓性白血病 (GI50 100nM) 细胞中。在一组具有血液学或实体瘤起源的癌症衍生细胞系中,AZD5991 优先杀死血液细胞[1][3]。
|
|
体内研究 (In Vivo) |
单次耐受性良好的剂量后,AZD5991 单独使用或与硼替佐米或维奈托克联合使用时,在多种多发性骨髓瘤和急性髓性白血病模型中表现出强大的体内抗肿瘤活性,肿瘤完全消退。这些体内研究中 caspase-3 和 PARP 的裂解表明,AZD5991 的细胞毒活性与线粒体凋亡途径的激活密切相关[1]。
|
|
细胞实验 |
MOLP-8 细胞用 AZD5991 或 DMSO 对照处理 30 分钟。然后将样品离心,将沉淀重悬于冰冷的裂解缓冲液中,并在冰上孵育 20 分钟,每 5 分钟涡旋一次。离心样品后,测量蛋白质浓度。在 4°C 下旋转孵育抗 Mcl-1 抗体过夜之前,使用旋转和 50% Protein A/G 磁珠浆液在 4°C 下将样品预净化 30 分钟。之后,加入Protein A/G磁珠并在4℃下旋转1小时。每个 IP 沉淀物均添加 10% 的样品还原剂,然后用裂解缓冲液/PBS (1:1) 洗涤四次,然后进行蛋白质印迹分析。
|
|
动物实验 |
|
|
参考文献 |
分子式 |
C35H34CLN5O3S2
|
---|---|
分子量 |
672.2592
|
精确质量 |
671.18
|
元素分析 |
C, 62.53; H, 5.10; Cl, 5.27; N, 10.42; O, 7.14; S, 9.54
|
CAS号 |
2143061-81-6
|
相关CAS号 |
AZD-5991 Racemate;2143010-83-5;AZD-5991 (S-enantiomer);2143061-82-7
|
外观&性状 |
Solid powder
|
SMILES |
CC1=C2C(=NN1C)CSCC3=NN(C(=C3)CSC4=CC5=CC=CC=C5C(=C4)OCCCC6=C(N(C7=C6C=CC(=C27)Cl)C)C(=O)O)C
|
InChi Key |
KBQCEQAXHPIRTF-UHFFFAOYSA-N
|
InChi Code |
InChI=1S/C35H34ClN5O3S2/c1-20-31-29(38-40(20)3)19-45-17-22-15-23(41(4)37-22)18-46-24-14-21-8-5-6-9-25(21)30(16-24)44-13-7-10-26-27-11-12-28(36)32(31)33(27)39(2)34(26)35(42)43/h5-6,8-9,11-12,14-16H,7,10,13,17-19H2,1-4H3,(H,42,43)
|
化学名 |
17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(36),4(38),6,11,14,16,18,20,23,29(37),30,32,34-tridecaene-23-carboxylic acid
|
别名 |
AZD 5991; AZD-5991; AZD5991
|
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) |
DMSO: 100~250 mg/mL (148.8~371.9 mM)
|
---|---|
溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.08 mg/mL (3.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 2.08 mg/mL (3.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (3.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: ≥ 2.08 mg/mL (3.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. 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 | 1.4875 mL | 7.4376 mL | 14.8752 mL | |
5 mM | 0.2975 mL | 1.4875 mL | 2.9750 mL | |
10 mM | 0.1488 mL | 0.7438 mL | 1.4875 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) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03218683 | Terminated | Drug: AZD5991 + Venetoclax Drug: AZD5991 |
Relapsed or Refractory Acute Myeloid Leukemia (AML) |
AstraZeneca | August 2, 2017 | Phase 1 |
Hematological cell lines are preferentially sensitive to AZD5991. th> |
---|
AZD5991 causes tumor regression in AML models.Nat Commun.2018 Dec 17;9(1):5341. td> |
AZD5991 exhibits potent anti-tumor efficacy in MM models.Nat Commun.2018 Dec 17;9(1):5341. td> |