254753-54-3

Usage

Uses

Used in Anticancer Applications:
Monastrol is used as an antineoplastic agent for treating various cancer cell lines, such as MDA-MB-231 cells and mouse myeloma cell line SP 2/0. It induces apoptosis and helps elucidate the role of metabotropic glutamate receptor 3 (Grm3) in apoptosis.
Used in Drug Delivery Systems:
Monastrol is used as a cell-permeable small molecule inhibitor of the mitotic kinesin, Eg5, which arrests cells in mitosis with monoastral spindles. This property makes it a valuable tool in the development of drug delivery systems targeting cancer cells.
Used in Cellular Models of Learning and Memory:
Monastrol is used as a mimic of amyloid β effects on long term potentiation in cellular models of learning and memory, providing insights into the underlying mechanisms of these processes.
Used in Axon Regeneration Research:
Monastrol is used to enhance the regeneration of adult axons, making it a potential candidate for the development of treatments targeting nerve damage and repair.
Chemical Properties:
Monastrol is a crystalline solid with a molecular formula of C15H25N3O6 and a molecular weight of 327.38 g/mol.

Biological Activity

Potent, cell-permeable, small molecule mitosis inhibitor that does not interact with tubulin. Arrests cells in mitosis and specifically inhibits the motility of the mitotic kinesin Eg5, a motor protein required for mitotic spindle formation and maintenance (IC 50 = 14 μ M).

Biochem/physiol Actions

Monastrol is a potent, cell-permeant inhibitor of mitosis. Monastrol arrested cells are characterized by monopolar spindles. This phenotype is induced through specific disruption of mitotic molecular motor kinesin Eg5 with IC50 at 14 μM. No effect on other motor proteins and tubulin.

References

1) Mayer?et al. (1999), Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen; Science,?286?971 2) Kapoor?et al.?(2000),?Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of mitotic kinesin, Eg5; J. Cell Biol.,?150?975 3) Ari?et al.?(2014),?Alzheimer amyloid beta inhibition of Eg5/kinesin 5 reduces neurotrophin and/or transmitter receptor function; Neurobiol. Aging,?35?1839 4) Lin?et al. (2011),?Inhibition of Kinesin-5, a microtubule-based motor protein, as a strategy for enhancing regeneration of adult axons; Traffic,?12?269

InChI:InChI=1/C14H16N2O3S/c1-3-19-13(18)11-8(2)15-14(20)16-12(11)9-5-4-6-10(17)7-9/h4-7,12,17H,3H2,1-2H3,(H2,15,16,20)

Upstream product

• 37622-16-5 thiouronium hydrogensulfate 
• 141-97-9 ethyl acetoacetate 
• 100-83-4 meta-hydroxybenzaldehyde 
• 1147550-11-5 ammonium thiocyanate 
• 329689-23-8 monastrol 
• 17356-08-0 thiourea 
• 1243989-69-6 C₁₈H₂₂N₂O₄S 
• 1243989-70-9 C₁₈H₂₂N₂O₄S 
• 482655-63-0 ethyl 4-(3-((tert-butyldimethylsilyl)oxy)phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 96013-95-5 3-(tert-butyl-dimethyl-sylanyloxy)benzaldehyde 
• 482655-65-2 (S)-3-((2R,3R,4R,5R)-3,4-Bis-benzoyloxy-5-benzoyloxymethyl-tetrahydro-furan-2-carbonyl)-4-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester 
• 482655-64-1 (R)-3-((2R,3R,4R,5R)-3,4-Bis-benzoyloxy-5-benzoyloxymethyl-tetrahydro-furan-2-carbonyl)-4-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester 

Downstream Products

• 1228007-59-7 C₁₉H₂₂N₂O₆S 

Relevant academic research and scientific papers

Synthesis and Fluorescence Properties of new Monastrol Analogs Conjugated Fluorescent Coumarin Scaffolds

A mild and efficient method has been used for the synthesis of ethyl 4-(3-hydroxphenyl)-6-methyl-2-thioxo-1,3-dihydroprimidine-5-carboxylate (monastrol) (2), via Biginelli reaction. Alkylation of 2 with the fluorescent coumarin 3 afforded the new thioethe

Highly enantioselective organocatalytic Biginelli reaction

A series of binol- and H8-binol-based phosphoric acids have for the first time been evaluated for their ability to catalyze Biginelli reactions of aldehydes, thiourea or urea, and β-keto esters. A new chiral phosphoric acid, derived from 3,3′-d

X-ray structure, conformational analysis, enantioseparation, and determination of absolute configuration of the mitotic kinesin Eg5 inhibitor monastrol

The conformational features of the mitotic kinesin Eg5 inhibitor monastrol were investigated by computational (AM1, HF/3-21G*), X-ray diffraction, and NMR studies showing that monastrol is a conformationally highly flexible molecule. Racemic monastrol was

Grindstone chemistry: A highly efficient and green method for synthesis of 3,4-dihydropyrimidin-2-(1H)-ones by l-tyrosine as an organocatalyst: A combined experimental and DFT study

A single step, mild, environmentally friendly green method has been developed for the synthesis of physiologically active 3,4-dihydropyrimidin-2- (1H)-ones employing l-tyrosine as catalyst under solvent-free conditions at room temperature via grinding. Th

Integration of high speed microwave chemistry and a statistical 'design of experiment' approach for the synthesis of the mitotic kinesin Eg5 inhibitor monastrol

The rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol has been performed using multicomponent chemistry and combining microwave-assisted synthesis and a statistical design of experiments (DoEs) approach. By variation of the solvent, catalys

Application of design of experiments (Doe) approach for the optimization of phase-transfer catalyzed biginelli dihydropyrimidinone (dhpm) synthesis

The conventional Biginelli synthesis is more cumbersome and produces lower yields. Several improved methods are reported in the literature to replace the Biginelli catalyst. The design of biocompatible organic transformation is a major concern and a versa

Amine-functionalized nano-NaY zeolite for the synthesis of N-acetyl pyrazoles and dihydropyrimidines

An efficient base-catalyzed synthesis of dihydropyrimidines and N-acetyl pyrazoles is reported using 1-(2-aminoethyl)piperazine-modified nano-NaY zeolite (ZeSi–AP) under mild and green conditions. The structure of the catalyst was identified by using FT-IR, XRD, TGA, DTA, DLS, SEM, TEM, and elemental analyses. This heterogeneous catalyst has many benefits, such as a simple work-up procedure, high product yield, and it is easily regenerated and reused at least for four cycles without losing its activity.

A novel H2S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels

A new alleged monastrol-H2S releasing hybrid, named MADTOH, was designed based on the structure of monastrol (M) and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) and synthesized in 7.8% overall yield. MADTOH was shown to be an H2S donor under physiological conditions. In addition, the hybrid causes a decrease in global calcium transient in cardiomyocytes similar to nifedipine (NIFE), taken as a positive control. Whole-cell voltage-clamp showed that MADTOH decreases L-type Ca2+ current in isolated ventricular cardiomyocytes.

New Strategy for Synthesis of Anticancer Active Piperastrol, Enastron Using Ammonium Sulfocyanate

This report describes an efficient and mild approach for the synthesis of Piperastrol and Enastron via a one-pot three-component cyclocondensation reaction employing ammonium sul- focyanate (NH4SCN) on gram scale in isopropyl alcohol-PEG 400 medium. In this reaction, am?monium sulfocyanate is not only the reacting component but also accelerates the rate of reaction to afford Biginelli compounds. High yields, short reaction time and easy workup procedure are the key advantages of the present protocol. Ammonium sulfocyanate is readily available, cheaper, safer and industrially acceptable inorganic salt.

Concentrated solar radiation as a renewable heat source for a preparative-scale and solvent-free Biginelli reaction

A well-known Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was performed in an environmentally responsible manner. Large numbers of substrates were screened, and found to give excellent yields of the desired products. In