Monastrol
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MedKoo CAT#: 406240

CAS#: 329689-23-8

Description: Monastrol is a kinesin Eg5 inhibitor. Induction of apoptosis by monastrol is independent of the spindle checkpoint. Monastrol binds to the KSP-ADP complex, forming a KSP-ADP- monastrol ternary complex, which cannot bind to microtubules productively and cannot undergo further ATP-driven conformational changes.


Chemical Structure

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Monastrol
CAS# 329689-23-8

Theoretical Analysis

MedKoo Cat#: 406240
Name: Monastrol
CAS#: 329689-23-8
Chemical Formula: C14H16N2O3S
Exact Mass: 292.0882
Molecular Weight: 292.353
Elemental Analysis: C, 57.52; H, 5.52; N, 9.58; O, 16.42; S, 10.97

Price and Availability

Size Price Availability Quantity
50.0mg USD 450.0 2 Weeks
100.0mg USD 650.0 2 Weeks
200.0mg USD 1050.0 2 Weeks
500.0mg USD 1950.0 2 Weeks
1.0g USD 2750.0 2 Weeks
2.0g USD 4950.0 2 Weeks
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Related CAS #: 254753-54-3   329689-23-8  

Synonym: Monastrol

IUPAC/Chemical Name: ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

InChi Key: LOBCDGHHHHGHFA-UHFFFAOYSA-N

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)

SMILES Code: O=C(C1=C(C)NC(NC1C2=CC=CC(O)=C2)=S)OCC

Appearance: Solid powder

Purity: >98%

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: Monastrol is a potent and cell-permeable inhibitor of the mitotic kinesin Eg5 with an IC50 value of 14 μM.
In vitro activity: Monastrol is a small, cell-permeable molecule that arrests cells in mitosis by specifically inhibiting Eg5, a member of the Kinesin-5 family. Monastrol promotes a dramatic decrease in the observed rate of Eg5 association with microtubules, and ADP release is slowed without trapping the Mt.Eg5.ADP intermediate. Reference: J Biol Chem. 2005 Apr 1;280(13):12658-67. https://pubmed.ncbi.nlm.nih.gov/15665380/
In vivo activity: Monastrol retarded rat oocyte maturation by significantly (P < 0.05) decreasing germinal vesicle breakdown and increasing the frequencies of arrested metaphase I oocytes. Also, significant (P < 0.05) increases in the frequencies of monoastral spindles and chromosome displacement from the metaphase plate were found in oocytes during meiosis I. In metaphase II oocytes, monastrol significantly (P < 0.05) increased the frequencies of premature centromere separation and aneuploidy. Reference: Mutat Res. 2004 Apr 11;559(1-2):153-67. https://pubmed.ncbi.nlm.nih.gov/15066583/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 68.41
DMF:PBS (pH 7.2) (1:1) 0.5 1.71
DMSO 35.0 119.72
Ethanol 29.5 100.91

Preparing Stock Solutions

The following data is based on the product molecular weight 292.353 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Cochran JC, Gatial JE 3rd, Kapoor TM, Gilbert SP. Monastrol inhibition of the mitotic kinesin Eg5. J Biol Chem. 2005 Apr 1;280(13):12658-67. doi: 10.1074/jbc.M413140200. Epub 2005 Jan 23. PMID: 15665380; PMCID: PMC1356610. 2. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 1999 Oct 29;286(5441):971-4. doi: 10.1126/science.286.5441.971. PMID: 10542155. 3. Yoon SY, Choi JE, Huh JW, Hwang O, Lee HS, Hong HN, Kim D. Monastrol, a selective inhibitor of the mitotic kinesin Eg5, induces a distinctive growth profile of dendrites and axons in primary cortical neuron cultures. Cell Motil Cytoskeleton. 2005 Apr;60(4):181-90. doi: 10.1002/cm.20057. PMID: 15751098. 4. Mailhes JB, Mastromatteo C, Fuseler JW. Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes. Mutat Res. 2004 Apr 11;559(1-2):153-67. doi: 10.1016/j.mrgentox.2004.01.001. PMID: 15066583.
In vitro protocol: 1. Cochran JC, Gatial JE 3rd, Kapoor TM, Gilbert SP. Monastrol inhibition of the mitotic kinesin Eg5. J Biol Chem. 2005 Apr 1;280(13):12658-67. doi: 10.1074/jbc.M413140200. Epub 2005 Jan 23. PMID: 15665380; PMCID: PMC1356610. 2. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 1999 Oct 29;286(5441):971-4. doi: 10.1126/science.286.5441.971. PMID: 10542155.
In vivo protocol: 1. Yoon SY, Choi JE, Huh JW, Hwang O, Lee HS, Hong HN, Kim D. Monastrol, a selective inhibitor of the mitotic kinesin Eg5, induces a distinctive growth profile of dendrites and axons in primary cortical neuron cultures. Cell Motil Cytoskeleton. 2005 Apr;60(4):181-90. doi: 10.1002/cm.20057. PMID: 15751098. 2. Mailhes JB, Mastromatteo C, Fuseler JW. Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes. Mutat Res. 2004 Apr 11;559(1-2):153-67. doi: 10.1016/j.mrgentox.2004.01.001. PMID: 15066583.

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1: Kaur J, Dutta S, Chang KP, Singh N. A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol. J Antimicrob Chemother. 2013 Jan 4. [Epub ahead of print] PubMed PMID: 23292345.

2: Sashidhara KV, Avula SR, Sharma K, Palnati GR, Bathula SR. Discovery of coumarin-monastrol hybrid as potential antibreast tumor-specific agent. Eur J Med Chem. 2013 Feb;60:120-7. doi: 10.1016/j.ejmech.2012.11.044. Epub 2012 Dec 8. PubMed PMID: 23287057.

3: Soumyanarayanan U, Bhat VG, Kar SS, Mathew JA. Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study. Org Med Chem Lett. 2012 Jun 12;2(1):23. doi: 10.1186/2191-2858-2-23. PubMed PMID: 22691177; PubMed Central PMCID: PMC3518143.

4: Kamal A, Shaheer Malik M, Bajee S, Azeeza S, Faazil S, Ramakrishna S, Naidu VG, Vishnuwardhan MV. Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones. Eur J Med Chem. 2011 Aug;46(8):3274-81. doi: 10.1016/j.ejmech.2011.04.048. Epub 2011 May 5. PubMed PMID: 21620531.

5: Zhang Z, Ge Y, Zhang D, Zhou X. High-content analysis in monastrol suppressor screens. A neural network-based classification approach. Methods Inf Med. 2011;50(3):265-72. doi: 10.3414/ME09-01-0030. Epub 2010 Jul 5. PubMed PMID: 20602002.

6: Blasco MA, Thumann S, Wittmann J, Giannis A, Gröger H. Enantioselective biocatalytic synthesis of (S)-monastrol. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4679-82. doi: 10.1016/j.bmcl.2010.05.063. Epub 2010 May 25. PubMed PMID: 20566290.

7: Svetlik J, Veizerová L, Mayer TU, Catarinella M. Monastrol analogs: a synthesis of pyrazolopyridine, benzopyranopyrazolopyridine, and oxygen-bridged azolopyrimidine derivatives and their biological screening. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4073-6. doi: 10.1016/j.bmcl.2010.05.085. Epub 2010 May 26. PubMed PMID: 20542426.

8: Kaur J, Sundar S, Singh N. Molecular docking, structure-activity relationship and biological evaluation of the anticancer drug monastrol as a pteridine reductase inhibitor in a clinical isolate of Leishmania donovani. J Antimicrob Chemother. 2010 Aug;65(8):1742-8. doi: 10.1093/jac/dkq189. Epub 2010 Jun 2. PubMed PMID: 20519355.

9: Lakämper S, Thiede C, Düselder A, Reiter S, Korneev MJ, Kapitein LC, Peterman EJ, Schmidt CF. The effect of monastrol on the processive motility of a dimeric kinesin-5 head/kinesin-1 stalk chimera. J Mol Biol. 2010 May 28;399(1):1-8. doi: 10.1016/j.jmb.2010.03.009. Epub 2010 Mar 19. PubMed PMID: 20227420.

10: Tcherniuk S, van Lis R, Kozielski F, Skoufias DA. Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl-L-cysteine in tumor derived cell lines. Biochem Pharmacol. 2010 Mar 15;79(6):864-72. doi: 10.1016/j.bcp.2009.11.001. Epub 2009 Nov 6. PubMed PMID: 19896928.

11: Kulkarni MG, Chavhan SW, Shinde MP, Gaikwad DD, Borhade AS, Dhondge AP, Shaikh YB, Ningdale VB, Desai MP, Birhade DR. Zeolite catalyzed solvent-free one-pot synthesis of dihydropyrimidin-2(1H)-ones--a practical synthesis of monastrol. Beilstein J Org Chem. 2009;5:4. doi: 10.3762/bjoc.5.4. Epub 2009 Feb 4. PubMed PMID: 19259340; PubMed Central PMCID: PMC2649439.

12: Dallinger D, Kappe CO. Rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol using controlled microwave-assisted synthesis. Nat Protoc. 2007;2(2):317-21. PubMed PMID: 17406591.

13: Garcia-Saez I, DeBonis S, Lopez R, Trucco F, Rousseau B, Thuéry P, Kozielski F. Structure of human Eg5 in complex with a new monastrol-based inhibitor bound in the R configuration. J Biol Chem. 2007 Mar 30;282(13):9740-7. Epub 2007 Jan 23. PubMed PMID: 17251189.

14: Bevan DR, Garst JF, Osborne CK, Sims AM. Application of molecular modeling to analysis of inhibition of kinesin motor proteins of the BimC subfamily by monastrol and related compounds. Chem Biodivers. 2005 Nov;2(11):1525-32. PubMed PMID: 17191952.

15: Chin GM, Herbst R. Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is independent of the spindle checkpoint. Mol Cancer Ther. 2006 Oct;5(10):2580-91. PubMed PMID: 17041103.

16: Russowsky D, Canto RF, Sanches SA, D'Oca MG, de Fátima A, Pilli RA, Kohn LK, Antônio MA, de Carvalho JE. Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues. Bioorg Chem. 2006 Aug;34(4):173-82. Epub 2006 Jun 12. PubMed PMID: 16765411.

17: Müller C, Gross D, Sarli V, Gartner M, Giannis A, Bernhardt G, Buschauer A. Inhibitors of kinesin Eg5: antiproliferative activity of monastrol analogues against human glioblastoma cells. Cancer Chemother Pharmacol. 2007 Feb;59(2):157-64. Epub 2006 May 16. PubMed PMID: 16703323.

18: Krzysiak TC, Wendt T, Sproul LR, Tittmann P, Gross H, Gilbert SP, Hoenger A. A structural model for monastrol inhibition of dimeric kinesin Eg5. EMBO J. 2006 May 17;25(10):2263-73. Epub 2006 Apr 27. PubMed PMID: 16642039; PubMed Central PMCID: PMC1462975.

19: Maliga Z, Mitchison TJ. Small-molecule and mutational analysis of allosteric Eg5 inhibition by monastrol. BMC Chem Biol. 2006 Feb 27;6:2. PubMed PMID: 16504166; PubMed Central PMCID: PMC1448180.

20: Maliga Z, Xing J, Cheung H, Juszczak LJ, Friedman JM, Rosenfeld SS. A pathway of structural changes produced by monastrol binding to Eg5. J Biol Chem. 2006 Mar 24;281(12):7977-82. Epub 2006 Jan 23. PubMed PMID: 16434397.



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