S-trityl-L-Cysteine
(Synonyms: NSC 83265; S-Tritylcysteine; 3-Tritylthio-L-alanine) 目录号 : GC40932
An inhibitor of Eg5
Cas No.:2799-07-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S-trityl-L-Cysteine is a non-natural amino acid and an inhibitor of Eg5, also known as KSP and Kif11, a mitotic kinesin necessary for mitotic spindle formation. S-trityl-L-Cysteine inhibits the ATPase activity of Eg5 in basal and microtubule-stimulated states (IC50s = 1,000 and 140 nM, respectively). It is selective for Eg5 over nine other human kinesins in an enzyme-coupled assay. It reversibly inhibits Eg5-driven microtubule sliding velocity with an IC50 value of 500 nM using X. laevis recombinant Eg5. It induces cell cycle arrest in HeLa cells (IC50 = 700 nM), reversibly halting the cell cycle in the mitotic phase by inhibiting the separation of duplicated chromosomes and preventing bipolar spindle formation. S-trityl-L-Cysteine inhibits the growth of cancer cells in vitro when tested against the National Cancer Institute (NCI) 60 human cancer cell line panel (average GI50 = 1.3 µM) and in mouse xenograft models.
| Cas No. | 2799-07-7 | SDF | |
| 别名 | NSC 83265; S-Tritylcysteine; 3-Tritylthio-L-alanine | ||
| Canonical SMILES | N[C@H](C(O)=O)CSC(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3 | ||
| 分子式 | C22H21NO2S | 分子量 | 363.5 |
| 溶解度 | DMSO: slightly soluble,Methanol: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.751 mL | 13.7552 mL | 27.5103 mL |
| 5 mM | 0.5502 mL | 2.751 mL | 5.5021 mL |
| 10 mM | 0.2751 mL | 1.3755 mL | 2.751 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
S-trityl-L-Cysteine, a novel Eg5 inhibitor, is a potent chemotherapeutic strategy in neuroblastoma
Oncol Lett 2018 Jul;16(1):1023-1030.PMID:29963178DOI:10.3892/ol.2018.8755.
Eg5 is a member of the kinesin-5 family. It is involved in the formation of the bipolar spindle and serves a crucial role in mitosis; meaning that mitotic activation may serve as a chemotherapeutic strategy. However, the anticancer activity of Eg5 inhibitors in neuroblastoma remains uncharacterized. In the present study, the expression of Eg5 was examined in clinical tissue samples and neuroblastoma cell lines, SK-N-SH, SH-SY5Y and SK-N-BE2. Additionally, the antitumor activity of the Eg5 inhibitor, S-trityl-L-Cysteine (STLC), was confirmed in vitro. STLC could mediate cell apoptosis, as well as cell cycle arrest, in a dose-dependent manner, which may contribute toward its antitumor activity. STLC-mediated apoptosis and cell cycle arrest were triggered by activation of the mitogen-activated protein kinase and nuclear factor kB signaling pathways. These results suggested that STLC may have potential in the in vivo treatment of neuroblastoma.
Antiproliferative S-trityl-L-Cysteine -Derived Compounds as SIRT2 Inhibitors: Repurposing and Solubility Enhancement
Molecules 2019 Sep 10;24(18):3295.PMID:31510043DOI:10.3390/molecules24183295.
S-trityl-L-Cysteine (STLC) is a well-recognized lead compound known for its anticancer activity owing to its potent inhibitory effect on human mitotic kinesin Eg5. STLC contains two free terminal amino and carboxyl groups that play pivotal roles in binding to the Eg5 pocket. On the other hand, such a zwitterion structure complicates the clinical development of STLC because of the solubility issues. Masking either of these radicals reduces or abolishes STLC activity against Eg5. We recently identified and characterized a new class of nicotinamide adenine dinucleotide-dependent deacetylase isoform 2 of sirtuin protein (SIRT2) inhibitors that can be utilized as cytotoxic agents based on an S-trityl-l-histidine scaffold. Herein, we propose new STLC-derived compounds that possess pronounced SIRT2 inhibition effects. These derivatives contain modified amino and carboxyl groups, which conferred STLC with SIRT2 bioactivity, representing an explicit repurposing approach. Compounds STC4 and STC11 exhibited half maximal inhibitory concentration values of 10.8 ± 1.9 and 9.5 ± 1.2 μM, respectively, against SIRT2. Additionally, introduction of the derivatizations in this study addressed the solubility limitations of free STLC, presumably due to interruption of the zwitterion structure. Therefore, we could obtain drug-like STLC derivatives that work by a new mechanism of action. The new derivatives were designed, synthesized, and their structure was confirmed using different spectroscopic approaches. In vitro and cellular bioassays with various cancer cell lines and in silico molecular docking and solubility calculations of the synthesized compounds demonstrated that they warrant attention for further refinement of their bioactivity.
S-trityl-L-Cysteine is a reversible, tight binding inhibitor of the human kinesin Eg5 that specifically blocks mitotic progression
J Biol Chem 2006 Jun 30;281(26):17559-69.PMID:16507573DOI:10.1074/jbc.M511735200.
Human Eg5, responsible for the formation of the bipolar mitotic spindle, has been identified recently as one of the targets of S-trityl-L-Cysteine, a potent tumor growth inhibitor in the NCI 60 tumor cell line screen. Here we show that in cell-based assays S-trityl-L-Cysteine does not prevent cell cycle progression at the S or G(2) phases but inhibits both separation of the duplicated centrosomes and bipolar spindle formation, thereby blocking cells specifically in the M phase of the cell cycle with monoastral spindles. Following removal of S-trityl-L-Cysteine, mitotically arrested cells exit mitosis normally. In vitro, S-trityl-L-Cysteine targets the catalytic domain of Eg5 and inhibits Eg5 basal and microtubule-activated ATPase activity as well as mant-ADP release. S-trityl-L-Cysteine is a tight binding inhibitor (estimation of K(i,app) <150 nm at 300 mm NaCl and 600 nm at 25 mm KCl). S-trityl-L-Cysteine binds more tightly than monastrol because it has both an approximately 8-fold faster association rate and approximately 4-fold slower release rate (6.1 microM(-1) s(-1) and 3.6 s(-1) for S-trityl-L-Cysteine versus 0.78 microM(-1) s(-1) and 15 s(-1) for monastrol). S-trityl-L-Cysteine inhibits Eg5-driven microtubule sliding velocity in a reversible fashion with an IC(50) of 500 nm. The S and D-enantiomers of S-tritylcysteine are nearly equally potent, indicating that there is no significant stereospecificity. Among nine different human kinesins tested, S-trityl-L-Cysteine is specific for Eg5. The results presented here together with the proven effect on human tumor cell line growth make S-trityl-L-Cysteine a very attractive starting point for the development of more potent mitotic inhibitors.
Functional dextran amino acid ester particles derived from N-protected S-trityl-L-Cysteine
Colloids Surf B Biointerfaces 2019 Sep 1;181:561-566.PMID:31185448DOI:10.1016/j.colsurfb.2019.06.005.
This work describes the derivatization of dextran using N-(tert-butyloxycarbonyl)-S-(trityl)-L-cysteine in the presence of N,N'-carbonyldiimidazole (CDI) as a coupling agent. Homogeneous reactions in dimethyl sulfoxide allowed for an efficient coupling of the amino acid derivative to the polymer backbone. Derivatization was confirmed by infrared and 13C NMR spectroscopy, size exclusion chromatography and elemental analysis. The presence of hydrophobic protecting groups resulted in a product that can be shaped into water-insoluble particles stable in an aqueous environment and non-toxic for lung epithelial cells. It is suggested that materials composed of ester bonds between amino acids and polysaccharides are useful for targeted drug delivery, bio-imaging or surface functionalization.
Photocontrol of the mitotic kinesin Eg5 using a novel S-trityl-L-Cysteine analogue as a photochromic inhibitor
J Biochem 2014 Apr;155(4):257-63.PMID:24451491DOI:10.1093/jb/mvu004.
Because the mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. A number of specific and potent inhibitors of Eg5 are known. S-trityl-L-Cysteine is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. The trityl group of S-trityl-L-Cysteine was shown to be a key moiety required for potent inhibition. In this study, we synthesized a novel photochromic S-trityl-L-Cysteine analogue, 4-(N-(2-(N-acetylcysteine-S-yl) acetyl) amino)-4'- (N-(2-(N-(triphenylmethyl)amino)acetyl)amino)azobenzene (ACTAB), composed of a trityl group, azobenzene and N-acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different wavelengths in the visible range, 400 and 480 nm. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared with cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.