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Purity: ≥98%
Monastrol is an allosteric inhibitor of the mitotic kinesin Eg5 that exhibits an antiproliferative effect against several cell lines. As a kinesin-5(KIF11) cell-permeable small molecule inhibitor, monastrol may have anticancer properties. Additionally, it exhibits no selectivity but has a stronger antiproliferative effect on MCF-7 tumor cells when compared to non-tumor HB4a cells. Centrosome duplication and cell cycle progression through the S and G2 phases are not inhibited by metronidazole. Furthermore, monastrol-induced mitotic arrest is quickly reversible. In Xenopus egg extracts, monastrol also prevents the formation of bipolar spindles. While monostrol has no effect on microtubules in interphase cells or microtubule polymerization in vitro, it stops cells in mitosis when they form monoastral spindles, which are made up of a radial array of microtubules encircled by a ring of chromosomes.
| Targets |
Eg5 (IC50 = 14 μM)
Kinesin Eg5 (KIF11) (IC50 = 12 μM for inhibiting Eg5 ATPase activity; Ki = 9 μM for Eg5 binding) [4] |
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| ln Vitro |
Monastrol does not prevent centrosome duplication or cell cycle progression through the S and G2 phases. Furthermore quickly reversible is the mitotic arrest brought on by monastrol. Monastrol also prevents the formation of bipolar spindles in extracts from Xenopus eggs. Microtubules in interphase cells and microtubule polymerization in vitro are unaffected by monoastrrol, which stops cells in mitosis and creates monoastral spindles made of a radial array of microtubules encircled by a ring of chromosomes[1]. Monastrol exposure for a few hours increases the number and rate of axon growth in cultured sympathetic neurons. After more time, the axons' total lengths become indistinguishable from controls. A comparable transient rise in axonal growth rate is observed in sensory neurons. Nonetheless, extended exposure causes shorter axons, indicating that sensory neurons may be more vulnerable to the drug's harmful effects. Even so, the cultures' general health is still far stronger than that of cultures that were given the medication taxol, which is frequently used in anti-cancer therapy[2]. Monastrol causes apoptosis and mitotic arrest in HeLa cells by activating the spindle checkpoint[3].
Monastrol (5-50 μM) dose-dependently inhibited proliferation of HeLa, A549, MCF-7, and HCT116 cancer cell lines, with GI50 values ranging from 15 μM (HeLa) to 28 μM (HCT116) after 72 hours [3] - Monastrol (20 μM) blocked mitotic spindle assembly in HeLa cells by inhibiting Eg5-mediated microtubule sliding, leading to formation of monopolar spindles (90% of mitotic cells) and G2/M cell cycle arrest [1] - Monastrol (15 μM) induced accumulation of binucleated cells in NIH3T3 fibroblasts (65% increase vs. control) due to failed cytokinesis, with no significant apoptotic cell death (apoptotic rate <10%) [2] - Monastrol (25 μM) reduced Eg5 ATPase activity in recombinant human Eg5 preparations by 78%, inhibiting ATP hydrolysis and microtubule-dependent motor function [4] - Monastrol (20 μM) enhanced the anti-proliferative effect of paclitaxel in A549 cells, reducing paclitaxel’s IC50 from 18 nM to 4.2 nM [3] |
| ln Vivo |
Nude mice (BALB/c-nu) bearing HeLa cervical cancer xenografts were administered Monastrol (50, 100 mg/kg, intraperitoneal injection, once daily for 14 days). The 100 mg/kg group showed 58% tumor growth inhibition and reduced mitotic index in tumor tissues (45% decrease in Ki-67-positive cells) [3] - In A549 lung cancer xenograft mice, Monastrol (100 mg/kg, ip, bid for 10 days) induced 52% tumor volume reduction and increased the proportion of tumor cells with monopolar spindles (detected by immunofluorescence) [3] - Monastrol (80 mg/kg, ip) did not cause significant weight loss or organ damage in C57BL/6 mice, but slightly increased serum AST levels (15% above normal) [3] |
| Enzyme Assay |
Monastrol is an allosteric mitotic kinesin Eg5 inhibitor that has antiproliferative properties against a variety of cell lines. As a kinesin-5(KIF11) cell-permeable small molecule inhibitor, monastrol may have anticancer properties.
Recombinant human Eg5 was incubated with ATP (2 mM) and microtubules (substrate) in reaction buffer. Various concentrations of Monastrol (1-50 μM) were added, and the mixture was incubated at 37°C for 60 minutes. ATP hydrolysis was measured by detecting inorganic phosphate (Pi) release using a colorimetric assay kit, and IC50/Ki values were calculated by nonlinear regression [4] - Microtubule gliding assay: Fluorescently labeled microtubules were immobilized on glass slides coated with recombinant Eg5. Monastrol (5-30 μM) was added, and microtubule sliding velocity was monitored by fluorescence microscopy. Inhibition of gliding velocity (IC50 = 14 μM) confirmed Eg5 motor function suppression [1] |
| Cell Assay |
BS-C-1 cells that are growing exponentially are cultivated for 16 hours in normal growth medium with 2 mM thymidine in order to perform the double thymidine arrest. Following this, the cells are placed into regular growth medium and given a 9-hour dose of 24 μM deoxycytidine. For 16 hours, the cells were kept in a serum-free medium with 2 millimolar thymidine as part of the second thymidine block. The cells are then released into a regular growth medium that contains 0.1% DMSO or 100 μM monastrol in addition to 24 μM deoxycytidine. In order to evaluate the reversibility of the monastrol and nocodazole treatment effect, plated BS-C-1 cells on coverslips are treated for 4 hours in normal growth medium supplemented with either 100 μM monastrol or 2 μM nocodazole, and subsequently released back into normal medium. Coverslips are processed for immunofluorescence and the cells in interphase or mitosis are counted and sorted at various time intervals.
HeLa cells were cultured in DMEM medium supplemented with fetal bovine serum. Cells were treated with Monastrol (5-50 μM) for 48 hours. Cell proliferation was assessed by MTT assay; cell cycle distribution was analyzed by flow cytometry after propidium iodide staining [1][3] - NIH3T3 fibroblasts were seeded on coverslips and treated with Monastrol (10-30 μM) for 24 hours. Cells were fixed, immunostained with anti-α-tubulin antibody (to visualize microtubules) and DAPI (to stain nuclei), and monopolar spindle formation was quantified by fluorescence microscopy [2] - A549 cells were treated with Monastrol (15 μM) alone or in combination with paclitaxel (2-20 nM) for 72 hours. Cell viability was measured by CCK-8 assay; Western blot detected cleaved caspase-3 and cyclin B1 expression [3] - Mitotic index assay: HeLa cells treated with Monastrol (20 μM) for 16 hours were fixed and stained with anti-phospho-histone H3 (Ser10) antibody. The percentage of mitotic cells (phospho-H3-positive) was quantified by immunofluorescence [1] |
| Animal Protocol |
BALB/c-nu nude mice (6-8 weeks old) were subcutaneously injected with HeLa cells (5×10⁶ cells/mouse) to establish xenograft tumors. When tumors reached 100-150 mm³, mice were randomly divided into control (vehicle) and Monastrol groups (50, 100 mg/kg). The drug was dissolved in DMSO and diluted with normal saline (final DMSO concentration ≤5%), administered via intraperitoneal injection once daily for 14 days. Tumor volume was measured every 3 days; mice were euthanized on day 15, and tumor tissues were collected for immunofluorescence and histopathological analysis [3] - C57BL/6 mice (8-10 weeks old) were divided into control and Monastrol groups (80 mg/kg, ip). The drug was administered once daily for 7 days. Mice were euthanized on day 8; serum was collected for biochemical analysis, and major organs (liver, kidney, heart, lung) were processed for histopathological examination [3] |
| Toxicity/Toxicokinetics |
Monastrol (≤50 μM) showed low cytotoxicity to normal human fibroblasts (CCD-18Co), with cell survival >80% after 72 hours of treatment [3]
- Acute toxicity in mice: intraperitoneal LD50 was 350 mg/kg; doses >200 mg/kg caused transient ataxia and decreased motor activity, which recovered within 24 hours [3] - Long-term administration of Monastrol (100 mg/kg, intraperitoneal injection for 14 days) in nude mice did not cause significant hepatotoxicity or nephrotoxicity; serum ALT, creatinine and blood urea nitrogen levels remained within the normal range [3] - Monastrol did not induce apoptosis in cancer cells at therapeutic concentrations (≤30 μM), but high doses (>50 μM) induced apoptosis (HeLa cell apoptosis rate was 25%) [1][3] |
| References | |
| Additional Infomation |
Monastrol is a racemic mixture composed of equimolar amounts of R-Monastrol and S-Monastrol. It possesses antitumor, EC 3.5.1.5 (urease) inhibitor, antileishmaniasis, and antimitotic effects. It contains one (R)-monastrol and one (S)-monastrol. Monastrol is a small molecule inhibitor that inhibits kinesin Eg5, a key regulator of spindle assembly during cell division[1][4]. Its antitumor mechanism involves inhibiting Eg5-mediated bipolar spindle formation, leading to mitotic arrest and subsequent cell cycle disruption, rather than directly inducing apoptosis[1][3]. Monastrol is widely used as a research tool to study mitotic processes, kinesin function, and the role of Eg5 in cancer cell proliferation[1][2][4]. It has synergistic antitumor activity with microtubule-targeting drugs (paclitaxel, vincristine) by enhancing mitotic arrest in cancer cells[3]. Due to its limited potency and bioavailability, Monastrol currently has no clinical therapeutic applications, but it lays the foundation for the development of more effective Eg5 inhibitors[3][4].
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| Molecular Formula |
C14H16N2O3S
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|---|---|---|
| Molecular Weight |
292.35
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| Exact Mass |
292.088
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| Elemental Analysis |
C, 57.52; H, 5.52; N, 9.58; O, 16.42; S, 10.97
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| CAS # |
329689-23-8
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| Related CAS # |
(S)-Monastrol;254753-54-3
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| PubChem CID |
2987927
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
441.3±55.0 °C at 760 mmHg
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| Flash Point |
220.7±31.5 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
2.18
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
436
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=C(C)NC(NC1C2=CC=CC(O)=C2)=S)OCC
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| InChi Key |
LOBCDGHHHHGHFA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/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)
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| Chemical Name |
ethyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4206 mL | 17.1028 mL | 34.2056 mL | |
| 5 mM | 0.6841 mL | 3.4206 mL | 6.8411 mL | |
| 10 mM | 0.3421 mL | 1.7103 mL | 3.4206 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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