MeisoindigoApoptosis inducer;potential agent for AML CAS# 97207-47-1 |
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| Cas No. | 97207-47-1 | SDF | Download SDF |
| PubChem ID | 5479433 | Appearance | Powder |
| Formula | C17H12N2O2 | M.Wt | 276.29 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | Dian III; N-Methylisoindigotin; Natura-α | ||
| Solubility | DMSO : ≥ 51 mg/mL (184.59 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (3E)-1-methyl-3-(2-oxo-1H-indol-3-ylidene)indol-2-one | ||
| SMILES | CN1C2=CC=CC=C2C(=C3C4=CC=CC=C4NC3=O)C1=O | ||
| Standard InChIKey | QNOCRUSVMMAKSC-CCEZHUSRSA-N | ||
| Standard InChI | InChI=1S/C17H12N2O2/c1-19-13-9-5-3-7-11(13)15(17(19)21)14-10-6-2-4-8-12(10)18-16(14)20/h2-9H,1H3,(H,18,20)/b15-14+ | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Meisoindigo(Natura-α; N-Methylisoindigotin; Dian III), a derivative of Indigo naturalis, might induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML).
IC50 value:
Target: apoptosis inducer
in vitro: Meisoindigo inhibited the growth of leukemic cells by inducing marked apoptosis and moderate cell-cycle arrest at the G(0)/G(1) phase. It down-regulated anti-apoptotic Bcl-2, and up-regulated pro-apoptotic Bak and Bax and cell-cycle related proteins, p21and p27. Furthermore, it induced myeloid differentiation, as demonstrated by morphologic changes, up-regulation of CD11b, and increased nitroblue tetrazolium reduction activity in all cell lines tested. In addition, meisoindigo down-regulated the expression of human telomerase reverse transcriptase and enhanced the cytotoxicity of conventional chemotherapeutic agents, cytarabine and idarubicin. As with the results from cell lines, meisoindigo also induced apoptosis, up-regulated p21 and p27, and down-regulated Bcl-2 in primary AML cells [1]. meisoindigo effectively inhibits HT-29 cell proliferation (IC(50) 4.3 mmol/L), arrests HT-29 cells in G2/ M phase and induces HT-29 cell apoptosis. The downstream genes and proteins of GSK-3beta(ser(9)) expression level decrease [2].
in vivo: The in vivo anti-leukemic activity of meisoindigo was also demonstrated by decreased spleen size in a dose-dependent manner [1]. Meisoindigo significantly inhibits the HT-29 xenograft tumors growth at the dose of 100 mg/kg. The mechanism of meisoindigo activity against HT-29 cells may be related to its inhibition of glycogen synthase kinase-3beta, GSK-3beta(ser(9)) phosphorylation in Wnt signaling pathway [2]. References: | |||||
Meisoindigo Dilution Calculator
Meisoindigo Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 3.6194 mL | 18.0969 mL | 36.1939 mL | 72.3877 mL | 90.4846 mL |
| 5 mM | 0.7239 mL | 3.6194 mL | 7.2388 mL | 14.4775 mL | 18.0969 mL |
| 10 mM | 0.3619 mL | 1.8097 mL | 3.6194 mL | 7.2388 mL | 9.0485 mL |
| 50 mM | 0.0724 mL | 0.3619 mL | 0.7239 mL | 1.4478 mL | 1.8097 mL |
| 100 mM | 0.0362 mL | 0.181 mL | 0.3619 mL | 0.7239 mL | 0.9048 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Meisoindigo is a potential agent for acute myeloid leukemia [1].
Meisoindigo is a synthetic modification of indirubin. It has been used for chronic myeloid leukemia in China with less toxicity. In the in vitro assay, it can inhibit synthesis of DNA and RNA and the assembly of microtubules. It is also reported to have efficacy in acute myeloid leukemia. In the AML cell lines, HL-60, NB4 and U937, meisoindigo induces apoptosis in both caspase-dependent and -independent pathways. The effect induced by meisoindigo is likely mediated through the intrinsic mitochondrial pathway. Meisoindigo also induces cell cycle arrest with more cells in sub-G1 and G0/G1 phases and fewer cells in the S phase. Besides, meisoindigo is found to induce differentiation in HL-60 and NB4 cell lines. The expression of hTERT can be down-regulated by meisoindigo, which can enhance the anti-leukemic activity of chemotherapeutic agents. Moreover, meisoindigo shows a moderate anti-tumor efficacy in NOD/SCID mice injected with AML cells [1].
References:
[1] Lee CC, Lin CP, Lee YL, Wang GC, Cheng YC, Liu HE. Meisoindigo is a promising agent with in vitro and in vivo activity against human acute myeloid leukemia. Leuk Lymphoma. 2010 May;51(5):897-905.
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Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics.[Pubmed:25050545]
Int J Oncol. 2014 Oct;45(4):1724-34.
Meisoindigo has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia (CML) in China since the 1980s. In the present study, the in vitro antileukemic activity of Meisoindigo was investigated in acute promyelocytic leukemia (APL) cells, acute myeloid leukemia (AML) cells, and myelomonocytic leukemia cells (NB4, NB4.007/6, HL-60 and U937) comprising both retinoic acid-sensitive and retinoic acid-resistant cells. We found that Meisoindigo effectively inhibited the growth and/or proliferation of these four cell types at microM levels. The effects of Meisoindigo in these cells are related to its proliferation inhibition and apoptosis induction, and are independent of cell cycle arrest, indicating that Meisoindigo could be possible in the treatment of APL, AML and retinoic acid resistant APL. The in vivo pharmacokinetics of Meisoindigo and its major circulatory metabolites in rat plasma were then investigated by a newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The profiles of plasma concentration versus time were plotted and the relevant pharmacokinetic parameters were calculated for Meisoindigo and its reductive metabolites. The plasma concentrations of Meisoindigo after oral administration were much lower than the in vitro IC50s determined in the leukemic cells. The contradicting poor pharmacokinetic characteristics and the established clinical efficacy of Meisoindigo could indicate the presence of active metabolites in vivo.
[Mechanism about therapeutic effect of meisoindigo on psoriasis via down-regulation of the TLR4-TAK-NF-kappaB pathways].[Pubmed:23833936]
Yao Xue Xue Bao. 2013 Apr;48(4):503-7.
Meisoindigo is an indigo natural derivative commonly used in anti-cancer therapy. In the clinical application, it was also found to have good therapeutic effect on psoriasis. In order to further understand its mechanism of action, human normal keratinocyte cell line HaCaT and RAW 264.7 were used to identify if Meisoindigo could affect the inflammatory factors such as NO and other important cytokines which were highly involved in psoriasis. Our results indicated that Meisoindigo decreased the production of NO in LPS-stimulated RAW 264.7 cells and reduced the expression of cytokines in LPS-stimulated HaCaT cells. And TLR4-TAK-NF-kappaB was a possible pathway mainly involved in the attenuation of iNOS and pro-inflammatory cytokine production by Meisoindigo, which may take part in the therapeutic effect of Meisoindigo on psoriasis.
[Immuno-regulatory effect of 3'-meisoindigo in mice of various germlines].[Pubmed:21137371]
Zhong Yao Cai. 2010 Jul;33(7):1124-9.
OBJECTIVE: To investigate the effect of 3'-Meisoindigo on the proliferation and the biological function of the splenocyte and thymocyte of mouse, which were 8 weeks old masculinity BALB/c, C57BL/6 and F1 hybridization mouse. METHODS: Cells of thymus and spleen were harvested and prepared as the unicell suspension, then treated with 5, 10, 15, 20, 25 micromol/L 3'-Meisoindigo. The cell proliferation was by MTT method, concentration of IL-12 was dectected by ELISA method, the mRNA levels of Bcl-2 and CDK2 were decected by RT-PCR. The cell cycle, apoptosis ratio, death ratio and intracellular ROS concentration were detected by FCM method. The protein level of Bcl-2, CDK2 and Bax were detected by immumofluorescence method. RESULTS: 15, 20, 25 micromol/L 3'-Meisoindigo can inhibit the proliferation of thymocyte and splenocyte (P < 0.05). It had dose-dependent and time-dependent manner. 3'-Meisoindigo inhibit the secretion of IL-12, even at 5 micromol/L concentration. 15 micromol/L 3'-Meisoindigo decrease the mRNA level of Bcl-2 and CDK2, induced apoptosis and G2 arrestting of the thymocyte and splenocyte. (P < 0.05). The intracellular ROS level increased after treated by 3'-Meisoindigo at 15 micromol/L for 24 h (P < 0.05). There were no difference among three germ line mouse. CONCLUSION: Above 15 micromol/L, 3'-Meisoindigo can inhibit the proliferation and externalization function of thymocyte and splenocyte from different germ line mouse, meanwhile the mRNA and protein level of Bcl-2 and CDK2 decrease, the Bax protein expressed increased, the intracellular ROS level increase too.
Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.[Pubmed:27981893]
Pharm Biol. 2017 Dec;55(1):673-679.
CONTEXT: Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. OBJECTIVE: Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. MATERIALS AND METHODS: In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. RESULTS: In this study, using zebrafish-based chemical screening, we identified that the hit compound Meisoindigo (25 muM, 50 muM, 75 muM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that Meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of Meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that Meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. DISCUSSION AND CONCLUSION: Our results suggest that Meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.
