Thiocolchicine
(Synonyms: 硫代秋水仙碱) 目录号 : GC45039
An inhibitor of microtubule assembly
Cas No.:2730-71-4
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
Thiocolchicine is an inhibitor of microtubule assembly (IC50 = 2.5 µM) and a derivative of colchicine . It inhibits binding of colchicine to tubulin (Ki = 0.7 µM in a radioligand binding assay). Thiocolchicine inhibits proliferation of MDA-MB-231 and multidrug resistant (MDR) MCF-7 ADRr breast cancer cells (IC50s = 0.6 and 400 nM, respectively) as well MDR CEM-VBL leukemia cells (IC50 = 50 nM).
| Cas No. | 2730-71-4 | SDF | |
| 别名 | 硫代秋水仙碱 | ||
| Canonical SMILES | O=C1C(SC)=CC=C2C([C@@H](NC(C)=O)CCC3=C2C(OC)=C(OC)C(OC)=C3)=C1 | ||
| 分子式 | C22H25NO5S | 分子量 | 415.5 |
| 溶解度 | DMSO: soluble,Ethanol: soluble,Methanol: soluble | 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 | 2.4067 mL | 12.0337 mL | 24.0674 mL |
| 5 mM | 0.4813 mL | 2.4067 mL | 4.8135 mL |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4067 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。
Self-assembling Releasable Thiocolchicine-Diphenylbutenylaniline Conjugates
ACS Med Chem Lett 2019 Jan 4;10(4):611-614.PMID:30996805DOI:10.1021/acsmedchemlett.8b00605.
The design and the synthesis of new self-assembling conjugates is reported. The target compounds are characterized by the presence of a self-immolative linker that secures a controlled release induced by lipase cleavage. 4-(1,2-Diphenylbut-1-en-1-yl)aniline is used as a self-assembling inducer and amino-thiocolchicine as prototype of drug. The release of Thiocolchicine derivative has been demonstrated in vitro in the presence of porcine pancreatic lipase and Celite-supported lipase. The formation of nanoparticles is confirmed by dynamic light scattering, atomic force microscopy, and fluorescence microscopy. The antiproliferative activity has been proved on two human cancer cell lines.
Thiocolchicine dimers: a novel class of topoisomerase-I inhibitors
Biochem Pharmacol 2005 Jan 1;69(1):113-21.PMID:15588720DOI:10.1016/j.bcp.2004.09.004.
During a cellular screening of Thiocolchicine analogs, Thiocolchicine dimers resulted particularly active in cisplatin-resistant A2780-CIS cells. In order to discover by which mechanism(s) Thiocolchicine dimers overcame cisplatin resistance, p53, p21waf1 and MLH1 were assessed by Western blot. Results pointed out that, when combined with cisplatin, dimers increased the amount of all the three proteins with respect to the levels obtained by single drug exposure, thereby suggesting an interference in the process of repair of the cisplatin-induced DNA lesions. Moreover, in isolated nuclei drugs were able to produce DNA breaks, as demonstrated by Comet assay, thereby proving that the compounds were able to target cell nucleus independently from microtubules. Since Topo-I (topoisomerase I) is directly involved in the DNA repair and such activity is overexpressed in cisplatin-resistant cells, Topo-I was investigated as a potential target. Using DNA relaxation assay, Thiocolchicine dimers inhibited Topo-I, a property not shared by Thiocolchicine. At variance with camptothecin, dimers did not produce cleavable complexes, thereby indicating that Topo-I inhibition occurs upstream of the religation step. To assess the mechanism of inhibition, an electrophoretic mobility shift assay between DNA and Topo-I was performed and revealed that Thiocolchicine dimers specifically interfere with binding of Topo-I to DNA. The interference is specific since the same compounds did not modulate DNase activity and did not act as intercalating agents in the DNA unwinding assay. Finally, behaviour of dimers as spindle poisons was investigated and no relevant changes with respect to Thiocolchicine in terms of interaction with microtubules were found.
Synthesis of Thiocolchicine amine derivatives and evaluation of their antiproliferative activity
Bioorg Med Chem Lett 2021 Nov 15;52:128382.PMID:34592435DOI:10.1016/j.bmcl.2021.128382.
A series of 22 amine analogs of Thiocolchicine were synthesized using the reductive amination reaction. The antiproliferative activities of these compounds were tested against four tumor cell lines as well as one normal cell line. The tested analogs exhibited IC50 values in the nanomolar range accompanied by high selectivity indexes, and most importantly, they were able to break the drug resistance of the human colon adenocarcinoma resistant cell line (LoVo/DX). Also, a correlation between the antiproliferative activity and physicochemical properties of the novel compounds has been found.
Synthesis, antiproliferative activity and molecular docking of Thiocolchicine urethanes
Bioorg Chem 2018 Dec;81:553-566.PMID:30248507DOI:10.1016/j.bioorg.2018.09.004.
A number of naturally occurring compounds such as paclitaxel, vinblastine, combretastatin, and colchicine exert their therapeutic effect by changing the dynamics of tubulin and its polymer form, microtubules. The identification of tubulin as a potential target for anticancer drugs has led to extensive research followed by clinical development of numerous compounds from several families. In this paper we report on the design, synthesis and in vitro evaluation of a group of Thiocolchicine derivatives, modified at ring-B, labelled here compounds 4-14. These compounds have been obtained in a simple reaction of 7-deacetyl-10-thiocolchicine 3 with eleven different alcohols in the presence of triphosgene. These novel agents have been checked for anti-proliferative activity against four human cancer cell lines and their mode of action has been confirmed as colchicine binding site inhibition (CBSI) using molecular docking. Molecular simulations provided rational tubulin binding models for the tested compounds. On the basis of in vitro tests, derivatives 4-8 and 14 demonstrated the highest potency against MCF-7, LoVo and A549 tumor cell lines (IC50 values = 0.009-0.014 μM). They were more potent and characterized by a higher selectivity index than several standard chemotherapeutics including cisplatin and doxorubicin as well as unmodified colchicine. Further, studies revealed that colchicine and its several derivatives arrested MCF-7 cells in mitosis, while its selected derivatives caused microtubule depolymerization.
A prospective, randomized, single - blind study comparing intraplaque injection of Thiocolchicine and verapamil in Peyronie's Disease: a pilot study
Int Braz J Urol 2016 Sep-Oct;42(5):1005-1009.PMID:24893912DOI:10.1590/S1677-5538.IBJU.2015.0598.
Objectives: To compare the response to tiocolchicine and verapamil injection in the plaque of patients with Peyronie's disease. Materials and methods: Prospective, single-blind, randomized study, selecting patients who have presented Peyronie's disease for less than 18 months. Thiocolchicine 4mg or verapamil 5mg were given in 7 injections (once a week). Patients who had received any treatment for Peyronie's disease in the past three months were excluded. The parameters used were the International Index of Erectile Function (IIEF-5) score, analysis of the curvature on pharmaco-induced erections and size of the plaque by ultrasonography. Results: Twenty-five patients were randomized, 13 received Thiocolchicine and 12 were treated with verapamil. Both groups were statistically similar. The mean curvature was 46.7º and 36.2º before and after Thiocolchicine, respectively (p=0.019) and 50.4º and 42.08º before and after verapamil, respectively (p=0.012). The curvature improved in 69% of patients treated with Thiocolchicine and in 66% of those who received verapamil. Regarding sexual function, there was an increase in the IIEF-5 from 16.69 to 20.85 (p=0.23) in the Thiocolchicine group. In the verapamil group the IIEF-5 score dropped from 17.50 to 16.25 (p=0.58). In the Thiocolchicine group, the plaque was reduced in 61% of patients. In the verapamil group, 8% presented decreased plaque size. No adverse event was associated to Thiocolchicine. Conclusion: The use of Thiocolchicine in Peyronie's disease demonstrated improvement on penile curvature and reduction in plaque size. Thiocolchicine presented similar results to verapamil in curvature assessment. No significant side effects were observed with the use of tiocolchicine.