Isocryptotanshinone
(Synonyms: 异隐丹参酮) 目录号 : GC34178
Isocryptotanshinone是一种有效的信号传导与转录激活因子3(STAT3)和蛋白酪氨酸磷酸酶1B(PTP1B)的抑制剂，其对PTP1B的IC50值为56.1μM。
Cas No.:22550-15-8
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
Isocryptotanshinone is a potent signal transducer and activator of transcription 3 (STAT3) and protein tyrosine phosphatase 1B PTP1B inhibitor, with an IC50 of 56.1 μM for PTP1B.
It is showed that tanshinones significantly inhibited A549 proliferation and Isocryptotanshinone (ICTS) exhibits the strongest activity. Isocryptotanshinone inhibits the constitutive STAT3 and p-STAT3 (Y705) expression in concentration and time-dependent manners. Isocryptotanshinone dramatically inhibits the IL-6-stimulated expression of p-STAT3 (Y705) in a time-dependent manner[1].
[1]. Guo S, et al. Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells. J Drug Target. 2016 Dec;24(10):934-942. [2]. Han YM, et al. PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza. Biol Pharm Bull. 2005 Sep;28(9):1795-7.
| Cas No. | 22550-15-8 | SDF | |
| 别名 | 异隐丹参酮 | ||
| Canonical SMILES | O=C1C2=C(C3=C(C=C2)C(C)(C)CCC3)C(C4=C1[C@H](C)CO4)=O | ||
| 分子式 | C19H20O3 | 分子量 | 296.36 |
| 溶解度 | Soluble in DMSO | 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 | 3.3743 mL | 16.8714 mL | 33.7427 mL |
| 5 mM | 0.6749 mL | 3.3743 mL | 6.7485 mL |
| 10 mM | 0.3374 mL | 1.6871 mL | 3.3743 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。
(+)-Isocryptotanshinone derivatives and its simplified analogs as STAT3 signaling pathway inhibitors
Bioorg Chem 2022 Oct;127:106015.PMID:35849894DOI:10.1016/j.bioorg.2022.106015.
Isocryptotanshinone (ICTS), a natural product with potential signal transducer and activator of transcription-3 (STAT3) signaling pathway inhibitory activity, shows significant inhibitory activity against several tumors. In this study, a series of ICTS derivatives and simplified analogs containing a 1, 4-naphthoquinone core was designed, synthesized, and evaluated. The results demonstrated that most target compounds were potent STAT3 signaling pathway inhibitors based on their mechanism of inhibition of STAT3 phosphorylation. Moreover, based on the obtained data, the structure-activity relationship (SAR) was rationally deduced. Simultaneously, molecular docking of the compound 16r suggested its possible interaction mode with STAT3. To further verify anticancer activity, all target compounds were tested using HCT116, HepG2, MCF-7, A549, and U251 cell lines. Interestingly, compared with different tumor cell lines, the HCT-116 cell line was determined to be the most sensitive. Furthermore, compounds 21e, 16r, 28a, and 16e showed a dose-dependent inhibition of the growth of HCT116 cells. Thus, the SAR of ICTS derivatives and its simplified analogs was determined, and some of them were discovered to be potential anticancer candidates owing to their ability to inhibit the STAT3 signaling pathway.
Inhibitory effects of Isocryptotanshinone on gastric cancer
Sci Rep 2018 Jun 18;8(1):9307.PMID:29915371DOI:10.1038/s41598-018-27638-0.
Gastric cancer (GC) is one of the most common digestive malignancies globally, and the prognosis of patients with advanced tumors remains poor. Isocryptotanshinone (ICTS), isolated from Salvia miltiorrhiza, was found to inhibit the proliferation of lung and breast cancer cells. However, whether ICTS has anticancer activities against GC is unknown. In the present study, we reported that the proliferation of GC cells was inhibited by ICTS in a dose- and time-dependent manner. After treatment with ICTS, GC cells were arrested in the G1/G0 phase of cell cycle and the apoptotic cells were induced in a dose-dependent manner. Additionally, ICTS suppressed the expression of cell cycle- and apoptosis-associated proteins (e.g., Cyclin D1, phosphorylated Rb, E2F1, Mcl-1, Bcl-2, and Survivin). ICTS inhibited the phosphorylation of STAT3 in a dose-dependent manner. Down-regulated STAT3 attenuated the expression of Cyclin D1, p-Rb, and Survivin, which remarkably increased the sensitivity of ICTS in GC cells; overexpression of STAT3 restored the cell growth and proliferation and the protein expression suppressed by ICTS. ICTS also suppressed the xenograft tumor growth in BALB/c nude mice. Together, these data indicate that ICTS inhibits GC proliferation by inducing G1/G0 cell cycle arrest and apoptosis via inhibiting the STAT3 signaling pathway.
Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells
J Breast Cancer 2015 Jun;18(2):112-8.PMID:26155286DOI:10.4048/jbc.2015.18.2.112.
Purpose: Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. Methods: The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Results: ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. Conclusion: Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.
Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells
J Drug Target 2016 Dec;24(10):934-942.PMID:26904961DOI:10.3109/1061186X.2016.1157882.
Signal transducer and activator of transcription 3 (STAT3) is a potential drug target for chemotherapy. Cryptotanshinone (CTS) was identified as a potent STAT3 inhibitor, while the effect of other tanshinones remains unknown. In this study, the influence of eight tanshinones on STAT3 activity was initially screened and Isocryptotanshinone (ICTS) significantly inhibited STAT3 activity in a dual luciferase assay. ICTS inhibited the constitutive and inducible phosphorylation of STAT3 at Y705 without affecting the phosphorylation of STAT3 at S727 in A549 lung cancer cells. Furthermore, ICTS inhibited the nuclear translocation of STAT3. Compared with CTS, ICTS exhibited a stronger inhibitory effect on STAT3 phosphorylation and on A549 cytotoxicity. ICTS induced autophagy as evidenced by the accumulation of autophagic vacuoles and the increased expression of LC3 protein and autophagosomes. ICTS-induced cell death was partially reversed by the autophagy inhibitor chloroquine. The docking assay predicted that both ICTS and CTS bind the SH2 domain of STAT3. ICTS formed hydrogen bonds and pi-pi interaction with the nearby amino acid residues of Lys591, Arg609, and Ser636. These findings suggested that ICTS, a natural compound, is a potent STAT3 inhibitor. ICTS induced apoptosis and pro-death autophagy in A549 cells.
Tanshinones inhibit NLRP3 inflammasome activation by alleviating mitochondrial damage to protect against septic and gouty inflammation
Int Immunopharmacol 2021 Aug;97:107819.PMID:34098486DOI:10.1016/j.intimp.2021.107819.
Tanshinones, the active ingredients derived from the roots of Salvia miltiorrhiza, have been widely used as traditional medicinal herbs for treating human diseases. Although tanshinones showed anti-inflammatory effects in many studies, large knowledge gaps remain regarding their underlying mechanisms. Here, we identified 15 tanshinones that suppressed the activation of NLRP3 inflammasome and studied their structure-activity relationships. Three tanshinones (tanshinone IIA, Isocryptotanshinone, and dihydrotanshinone I) reduced mitochondrial reactive-oxygen species production in lipopolysaccharide (LPS)/nigericin-stimulated macrophages and correlated with altered mitochondrial membrane potentials, mitochondria complexes activities, and adenosine triphosphate and protonated-nicotinamide adenine dinucleotide production. The tanshinones may confer mitochondrial protection by promoting autophagy and the AMP-activated protein kinase pathway. Importantly, our findings demonstrate that dihydrotanshinone I improved the survival of mice with LPS shock and ameliorated inflammatory responses in septic and gouty animals. Our results suggest a potential pharmacological mechanism whereby tanshinones can effectively treat inflammatory diseases, such as septic and gouty inflammation.