S63845
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
S63845是MCL1的小分子抑制剂，Ki值小于1.2 nM [1].
Myeloid cell leukemia 1 （MCL1）是一个促存活蛋白，属于BCL-2家族。BCL-2家族蛋白是线粒体凋亡途径的重要调控子。MCL1在许多癌症中过表达，因此，靶向该蛋白的抑制剂可能杀死MCL1依赖性的癌细胞，包括多发性骨髓瘤，白血病和淋巴瘤细胞 [1]。
S63845是一种高选择性和有效的MCL1抑制剂。S63845结合人MCL1的KD值为0.19 nM。S63845可以更有效的杀死MCL1依赖性的H929多发性骨髓瘤细胞，效力是MCL1的抑制剂A-1210477的约1000倍。S63845也诱导caspase依赖的磷脂酰丝氨酸暴露、PARP裂解和线粒体细胞色素c释放。在HeLa细胞中，S63845干扰BAK和BAX与MCL1的结合。S63845通过直接抑制MCL1，活化BAX/BAK依赖的线粒体凋亡途径，从而杀死癌细胞 [1]。
在含有人类多发性骨髓瘤（H929和AMO1）异种移植物的免疫缺陷小鼠中，静脉注射S63845具有剂量依赖性的抗肿瘤活性，在H929和AMO1模型中的最大肿瘤生长抑制（TGImax）分别是103%和114% [1]。
Reference:
1.Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 19;538(7626):477-482.
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| Storage | Store at -20°C |
| M.Wt | 829.26 |
| Cas No. | 1799633-27-4 |
| Formula | C39H37ClF4N6O6S |
| Solubility | insoluble in H2O; ≥20 mg/mL in MeOH; ≥41.45 mg/mL in DMSO |
| Chemical Name | (S)-2-(((S)-5-(3-chloro-2-methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl)oxy)-3-(2-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | OC([C@@H](OC1=NC=NC2=C1[C@]([C@]3=C(C)C(Cl)=C(C=C3)OCCN4CCN(C)CC4)=C(C5=CC=C(F)O5)S2)CC6=CC=CC=C6OCC7=CC=NN7CC(F)(F)F)=O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验 [1]: | |
|
细胞系 |
血液病源性细胞系，骨髓瘤细胞系，人淋巴瘤和慢性骨髓性白血病细胞系 |
|
溶解方法 |
该化合物可溶于DMSO。若获取更高浓度的溶液，可在37°C下孵育10分钟，随后在超声波浴中摇匀。-20°C以下可储存数月。 |
|
反应时间 |
1-10 μM, 48 h, 37°C |
|
应用 |
S63845是MCL1的小分子抑制剂，Ki值小于1.2 nM。S63845有效作用于血液肿瘤来源的细胞系。S63845有效杀死MCL1依赖性H929多发性骨髓瘤细胞。在HeLa细胞中，S63845破坏BAK和BAX与MCL1的结合。在HCT-116结肠癌细胞株中，S63845诱导MCL1蛋白水平升高。在骨髓瘤细胞系中，一些对S63845高度敏感，IC50值小于0.1 μM，6种细胞系适度敏感，IC50值为0.1-1 μM，两种细胞系不敏感，IC50值大于1 μM。在人类淋巴瘤和慢性粒细胞白血病的11细胞系中：5种细胞系对S63845高度敏感，IC50值小于0.1 μM，3种细胞系中度敏感，IC50值为0.1-1 μM，3种细胞系对S63845不敏感，IC50值大于1 μM。在测试的八种AML细胞系中，所有细胞系对S63845敏感，IC50值为4-233 nM。 |
| 动物实验 [1]: | |
|
动物模型 |
人多发性骨髓瘤（H929和AMO1）异种移植小鼠 |
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剂量 |
静脉注射，25 mg/kg |
|
应用 |
在人多发性骨髓瘤（H929和AMO1）异种移植的免疫受损小鼠中，静脉注射S63845以剂量依赖性方式表现出抗肿瘤活性，在AMO1模型中，最大肿瘤生长抑制（TGImax）为114％，H929模型中为103％。在AMO1模型中，S63845（25 mg/kg）治疗后100天，在8只小鼠中有7只肿瘤完全消退。在具有Eμ-Myc小鼠淋巴瘤的免疫耐受性C57BL/6小鼠中，S63845（i.v. 25 mg/kg，5天）治愈70％的小鼠，且对正常组织没有明显的副作用。在MV4-11人类AML异种移植模型中，S63845（12.5 mg/kg）具有有效的活性，TGImax为86％。S63845（25 mg/kg）给药80天后，8只小鼠中的6只肿瘤完全消退。 |
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注意事项 |
由于实验环境的不同，实际溶解度可能与理论值略有不同，请测试室内所有化合物的溶解度。 |
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References: [1]. Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 19;538(7626):477-482. |
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质量控制和MSDS
- 批次:
化学结构
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