S130
目录号 : GC65307
S130 是一种高亲和力、选择性的半胱氨酸蛋白酶 ATG4B 的抑制剂, IC50 值为 3.24 µM。S130 可以抑制自噬通量。
Cas No.:1160852-22-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S130 is a high affinity, selective inhibitor of ATG4B (a major cysteine protease) with an IC50 of 3.24 µM. S130 suppresses autophagy flux[1].
S130 suppresses autophagy and activates apoptosis by inhibiting ATG4B, leads to enhanced cytotoxicity[1].S130 (10 μM; 6 hours) suppresses autophagy at the early LC3 priming step or late autolysosome degradation stage[1].S130 accumulates autolysosomes with more lipidated LC3[1].S130 (0-25 μM; 48 hours) induces cell death through inhibiting the activity of ATG4B at a dose higher than 6.3 µM. And such cytotoxicity might not cause cell death through necroptosis[1].Nutrient deprivation enhances S130-induced cytotoxicity[1].S130 (0-10μM; 24 hours) suppresses approximately 79% of the cleavage of full-length LC3-GST at the 10 µM, while no substrates were processed in ATG4B KO cells. S130 displays obvious inhibitory effects on ATG4B[1].
S130 (20 mg/kg; i.p.; daily; 3 weeks) suppresses tumor growth, and shows an efficient in vivo antitumor effect with a sound safety on vital organs[1].
[1]. Fu Y, et al. Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo. Autophagy. 2018 Sep 20:1-17.
| Cas No. | 1160852-22-1 | SDF | Download SDF |
| 分子式 | C24H25N3O2 | 分子量 | 387.47 |
| 溶解度 | DMSO : 125 mg/mL (322.61 mM; Need ultrasonic) | 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 | 2.5808 mL | 12.9042 mL | 25.8084 mL |
| 5 mM | 0.5162 mL | 2.5808 mL | 5.1617 mL |
| 10 mM | 0.2581 mL | 1.2904 mL | 2.5808 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。
Retraction
J Cell Biochem 2021 Nov;122 Suppl 1:S130.PMID:34342904DOI:10.1002/jcb.30117.
Retraction: "Receptor for advanced glycation end products reveals a mechanism regulating thyroid hormone secretion through the SIRT1/Nrf2 pathway," by Xiao-Jun Chen, Xiao-Hua Gong, Jin-Ping Jie, Wei-Hui Yu, Xiong Chen, Xuan Du, Qi Zhou, and Wen-Jun Wu, J Cell Biochem. 2019; 4582-4598: The above article, published online on 15 October 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcb.27747) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that the experimental data in the article could not be reproduced. Thus, the conclusions are considered to be invalid. The authors were not available for a final confirmation of the retraction.
Quantitative bioanalytical LC-MS/MS assay for S130 in rat plasma-application to a pharmacokinetic study
Bioanalysis 2019 Aug;11(16):1469-1481.PMID:31512492DOI:10.4155/bio-2019-0101.
Aim: An innovative Atg4B inhibitor, S130, exhibited a negative influence on colorectal cancer cells in vitro and in vivo. To assist reliable toxicodynamic and pharmacokinetic evaluation, an LC-MS/MS assay of S130 in rat plasma must be necessary. Results: An LC-MS/MS assay for determination of S130 in rat plasma has been first developed and fully verified whose values met the admissible limits as per the US FDA guidelines. Chromatographic separation was achieved by using an isocratic elution after 3 min. MS was conducted under the ESI+ mode fitted with selected reaction monitoring. The calibration curve proved acceptable linearity over 0.50-800 ng/ml. Conclusion: The developed LC-MS/MS assay of S130 in rat plasma is easily applicable in pharmacokinetics study and the further toxicological evaluation.
COVID-19-related Abdominal Aortic Thrombosis
J Coll Physicians Surg Pak 2021 Jul;31(Supp. 2):S130-S131.PMID:34271813DOI:10.29271/jcpsp.2021.Supp2.S130.
Thrombotic complications increase in novel coronavirus disease 2019 (COVID-19) patients. Most of these complications are associated with venous thromboembolism and pulmonary embolism; and arterial thrombosis is rare. Usually, arterial thrombosis affects peripheral arteries. The involvement of large vessels, such as aorta, is rare in the literature. Major artery thrombosis manifests with different additional complications. Contrast-enhanced abdominal computed tomography angiography (CTA) was performed on a patient, who was followed-up with COVID-19 due to gastrointestinal symptoms. Supra-celiac aortic thrombosis and splenic infarction were detected. This case is reported to share experience regarding our treatment approach in the light of the literature data. Key Words: Arterial thrombosis, Acute aortic thrombosis, COVID-19.
[Vegetarian diets in childhood]
Arch Argent Pediatr 2020 Aug;118(4):S130-S141.PMID:32677803DOI:10.5546/aap.2020.S130.
Parents who decide to change the usual diet of their children for a more restrictive one should know the risks and advantages of the chosen diet and receive information that helps them to offer their children a sufficient diet. Vegetarian diets can be adopted as long as they are planned by specialists with the inclusion of a wide variety of plant foods and fortified foods with the appropriate supplementation indicated at each stage. The objective of this document is to present the position of the Nutrition Committee of the Argentine Society of Pediatrics and to provide health professionals with adequate information to respond to the concerns of parents and patients who decide to choose a vegetarian diet as a modality of feeding. The challenges to betaken into account are identified, highlighting that without these considerations and proper monitoring these diets cannot be carried out safely in childhood.
Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo
Autophagy 2019 Feb;15(2):295-311.PMID:30176161DOI:10.1080/15548627.2018.1517073.
Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated in silico screening and in vitro assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.