97207-47-1

Usage

Uses

Used in Oncology:
Meisoindigo is used as an anticancer agent for the treatment of pancreatic ductal adenocarcinoma (PDACs), particularly in cases that are resistant to gemcitabine. It is effective in inhibiting the growth of cancer cells and has the potential to be a promising therapeutic candidate for PDAC treatment.
Used in Leukemia Treatment:
Meisoindigo is used as a treatment for leukemia, specifically for NB4, HL-60, and U937 leukemia cells, as well as primary acute myeloid leukemia (AML) cells. It halts the cell cycle at the G0/G1 phase, induces apoptosis, and promotes myeloid differentiation. Additionally, Meisoindigo potentiates the effects of cytarabine and idarubicin, enhancing the overall efficacy of leukemia treatment.
Used in Cancer-related Nausea and Vomiting Management:
Meisoindigo is used as a 5-HT3 receptor antagonist to prevent acute nausea and vomiting associated with emetogenic cancer chemotherapy. This application helps improve the quality of life for cancer patients undergoing chemotherapy by reducing the severity of these side effects.
Used in Angiogenesis Inhibition:
Meisoindigo (10 μM) is used to induce apoptosis, decrease adherence, and reduce the expression of vascular cell adhesion molecule-1 (VCAM-1) in ECV304 human vein endothelial cells. This suggests that Meisoindigo may have potential applications in inhibiting angiogenesis, a process crucial for tumor growth and metastasis.
Used in AML Mouse Xenograft Model:
In an HL-60 mouse xenograft model of AML, Meisoindigo (50-150 mg/kg per day) is used to decrease spleen size in a dose-dependent manner. This indicates that Meisoindigo may have potential applications in treating AML and reducing the associated symptoms in preclinical models.

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.

InChI:InChI=1/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+

Upstream product

• 59-48-3 2-oxoindole 
• 2058-74-4 1-methyl-1H-indole-2,3-dione 
• 61-70-1 N-methyl-2-indolinone 
• 91-56-5 indole-2,3-dione 
• 100-61-8 N-methylaniline 
• 3526-43-0 N-(4-methoxybenzyl)aniline 
• 120-72-9 indole 
• 75833-71-5 1'-methyl-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one 
• 58956-40-4 3-hydroxy-3-(1H-indol-3-yl)-1-methylindolin-2-one 
• 42366-35-8 hydroxyimino-N-phenylacetamide 
• 62-53-3 aniline 
• 16990-73-1 2-Hydroxyindole 

Relevant academic research and scientific papers

POLYMORPHIC FORM OF MEISOINDIGO AND MODIFIED FORMULATION OF MEISOINDIGO

The present invention relates to a novel crystal form, manufacturing procedures, pharmaceutical compositions, formulations and medicaments comprising a N-methylisoindigo crystalline, methods of preparation, and the use of the N-methylisoindigo crystalline to prepare a medicament to prevent cancer, or treat cancer or an inflammatory-related disease associated with pro-inflammatory cytokine expression and/or reduced expression of anti-inflammatory cytokines.

NaI-mediated divergent synthesis of isatins and isoindigoes: A new protocol enabled by an oxidation relay strategy

A new approach for the synthesis of isatins and isoindigoes by an inexpensive and environmentally friendly NaI-mediated transformation is disclosed. The selectivity could be switched by simply varying the solvent, and isatins (using THF) and isoindigoes (using DMSO) could be obtained in moderate to excellent yields.

Mild and efficient synthesis of isoindigo derivatives catalyzed by Lewis acid

A mild and efficient ZrCl4-catalyzed synthesis of isoindigo derivatives from isatins and indolin-2-ones in refluxing ethanol is described. A variety of new functionalized isoindigo derivatives are obtained by simple filtration. Lewis acid was f

Palladium(II) Acetate-Catalyzed Dual C–H Functionalization and C–C Bond Formation: A Domino Reaction for the Synthesis of Functionalized (E)-Bisindole-2-ones from Diarylbut-2-ynediamides

A domino reaction of palladium(II)-catalyzed dual C–H functionalization with subsequent intramolecular annulation is presented. This method provides a convenient synthesis of a range of symmetrical and unsymmetrical biologically important (E)-bisindole-2-ones under extremely mild reaction conditions – room temperature, green oxidant and no additive. The reaction mechanism is elucidated in light of the yield values as well as additional control experiment results. (Figure presented.).

Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3β (GSK-3β) phosphorylation inhibitors

A series of N-alkyl or aryl substituted isoindigo derivatives have been synthesized and their anti-proliferative activity was evaluated by Sulforhodamine B (SRB) assay. Some of the target compounds exhibited significant antitumor activity, including compounds 6h and 6k (against K562 cells), 6i (against HeLa cells) and 6j (against A549 cells). N-(p-methoxy-phenyl)-isoindigo (6k) exhibited a high and selective anti-proliferative activity against K562 cells (IC50 7.8 μM) and induced the apoptosis of K562 cells in a dose-dependent manner. Compound 6k arrested the cell cycle at S phase in K562 cells by decreasing the expression of cyclin A and CDK2, which played critical roles in DNA replication and passage through G2 phase. Moreover, compound 6k down-regulated the expression of p-GSK-3β (Ser9), β-catenin and c-myc proteins, up-regulated the expression of GSK-3β, consequently, suppressed Wnt/β-catenin signaling pathway and induced the apoptosis of K562 cells. The binding mode of compound 6k with GSK-3β was simulated using molecular docking tools. All of these studies gave a better understanding to the molecular mechanisms of this class of agents and clues to develop dual CDK2/GSK-3β (Ser9) phosphorylation inhibitors applied in cancer chemotherapy.

COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF INDIRUBIN AND ANALOGS THEREOF, INCLUDING MEISOINDIGO

The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo.

Efficient green synthesis of isoindigo derivatives using sulfonic-acid-functionalized nanoporous silica (SBA-Pr-SO3H) catalyst and study of their antimicrobial properties

An efficient green condensation reaction has been developed for synthesis of trans-isoindigo derivatives using SBA-Pr-SO3H with pore size of 6 nm as a heterogeneous nanoporous acid catalyst under solvent-free conditions. Isoindigo derivatives have many industrial applications, e.g., dyes, drugs, organic solar cells, and semiconductor memories. The antimicrobial activities of these compounds have also been tested.

Synthesis and evaluation of functionalized isoindigos as antiproliferative agents

A series of functionalized isoindigos structurally related to meisoindigo (1-methylisoindigo), a therapeutic agent used for the treatment of a form of leukemia, were synthesized and evaluated for antiproliferative activities on a panel of human cancer cells. Two promising compounds (1 -phenpropylisoindigo and 1-(p-methoxy-phenethyl)-isoindigo) that were more potent than meisoindigo and comparable to 6bromoindirubin-3'-oxime on leukemic K562 and liver HuH7 cells were identified. Structure-activity relationships showed the importance of keeping one of the lactam NH in an unsubstituted state. Substitution of the other lactam NH with aryl or arylalkyl side chains retained or improved activity in most instances. An intact exocyclic double bond was also essential, possibly to maintain planarity and rigidity of the isoindigo scaffold. None of the compounds were found to inhibit CDK2 in an in vitro assay, in spite of reports linking the antiproliferative activities of meisoindigo and other isoindigos to CDK2 inhibition. Hence, these functionalized isoindigos disrupted cell growth and proliferation by other mechanistic pathways that did not involve CDK2 inhibition.