IUPAC/Chemical Name
(1R,3S,7S,8S,10S,12S,18R,Z)-7-hydroxy-12-((S,E)-1-hydroxy-3-((S)-4-methyl-3,6-dihydro-2H-pyran-2-yl)allyl)-3-methyl-5-methylene-9,13,22-trioxatricyclo[16.3.1.08,10]docosa-15,19-dien-14-one
InChi Key
MSBQEQDLFWWWMV-XZZGLLCESA-N
InChi Code
InChI=1S/C30H42O7/c1-19-12-13-34-23(15-19)10-11-25(31)27-18-28-30(37-28)26(32)17-21(3)14-20(2)16-24-8-4-6-22(35-24)7-5-9-29(33)36-27/h4-6,9-12,20,22-28,30-32H,3,7-8,13-18H2,1-2H3/b9-5-,11-10+/t20-,22-,23+,24-,25-,26-,27-,28-,30-/m0/s1
SMILES Code
C[C@@H](CC(C[C@@H]([C@@]1([H])[C@@](C[C@H]2[C@@H](O)/C=C/[C@H]3OCC=C(C)C3)([H])O1)O)=C)C[C@H]4O[C@H](C/C=C\C(O2)=O)C=CC4
Purity
>98% (or refer to the Certificate of Analysis)
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
Shelf Life
>3 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
Biological target:
Microtubule stabilzing agent.
In vitro activity:
Cells treated with laulimalide enter mitosis but arrest at prometaphase by generating multiple asters that coalesce into supernumerary poles and interfere with the integrity of the metaphase plate. Cells with a preformed bipolar spindle exist under heightened tension under laulimalide treatment, and chromosomes rapidly shear from the plate, even though the bipolar spindle is well-preserved.
Reference: Cell Cycle. 2012 Aug 15;11(16):3045-54. https://pubmed.ncbi.nlm.nih.gov/22871740/
In vivo activity:
This study used Caenorhabditis elegans embryos to investigate the acute effects of laulimalide on microtubules in vivo, with a direct comparison to paclitaxel. The results indicate that laulimalide induces a concentration-dependent, biphasic change in microtubule polymer dynamics in the C. elegans embryo.
Reference: PLoS One. 2013 Aug 2;8(8):e71889. https://pubmed.ncbi.nlm.nih.gov/23936530/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
10.3 |
19.99 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
514.66
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.
| 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. Bennett MJ, Chan GK, Rattner JB, Schriemer DC. Low-dose laulimalide represents a novel molecular probe for investigating microtubule organization. Cell Cycle. 2012 Aug 15;11(16):3045-54. doi: 10.4161/cc.21411. Epub 2012 Aug 8. PMID: 22871740; PMCID: PMC3442915.
2. Pryor DE, O'Brate A, Bilcer G, Díaz JF, Wang Y, Wang Y, Kabaki M, Jung MK, Andreu JM, Ghosh AK, Giannakakou P, Hamel E. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 2002 Jul 23;41(29):9109-15. doi: 10.1021/bi020211b. PMID: 12119025.
3. Bajaj M, Srayko M. Laulimalide induces dose-dependent modulation of microtubule behaviour in the C. elegans embryo. PLoS One. 2013 Aug 2;8(8):e71889. doi: 10.1371/journal.pone.0071889. PMID: 23936530; PMCID: PMC3732258.
In vitro protocol:
1. Bennett MJ, Chan GK, Rattner JB, Schriemer DC. Low-dose laulimalide represents a novel molecular probe for investigating microtubule organization. Cell Cycle. 2012 Aug 15;11(16):3045-54. doi: 10.4161/cc.21411. Epub 2012 Aug 8. PMID: 22871740; PMCID: PMC3442915.
2. Pryor DE, O'Brate A, Bilcer G, Díaz JF, Wang Y, Wang Y, Kabaki M, Jung MK, Andreu JM, Ghosh AK, Giannakakou P, Hamel E. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 2002 Jul 23;41(29):9109-15. doi: 10.1021/bi020211b. PMID: 12119025.
In vivo protocol:
1. Bajaj M, Srayko M. Laulimalide induces dose-dependent modulation of microtubule behaviour in the C. elegans embryo. PLoS One. 2013 Aug 2;8(8):e71889. doi: 10.1371/journal.pone.0071889. PMID: 23936530; PMCID: PMC3732258.
1: Zúñiga MA, Alderete JB, Jaña GA, Fernandez PA, Ramos MJ, Jiménez VA. Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association: A molecular modeling approach on the mechanism of microtubule stabilizing agents. Chem Biol Drug Des. 2018 May;91(5):1042-1055. doi: 10.1111/cbdd.13168. Epub 2018 Jan 23. PubMed PMID: 29316292.
2: Zúñiga MA, Alderete JB, Jaña GA, Jiménez VA. Structural insight into the role of Gln293Met mutation on the Peloruside A/Laulimalide association with αβ-tubulin from molecular dynamics simulations, binding free energy calculations and weak interactions analysis. J Comput Aided Mol Des. 2017 Jul;31(7):643-652. doi: 10.1007/s10822-017-0029-2. Epub 2017 Jun 9. PubMed PMID: 28597356.
3: Field JJ, Northcote PT, Paterson I, Altmann KH, Díaz JF, Miller JH. Zampanolide, a Microtubule-Stabilizing Agent, Is Active in Resistant Cancer Cells and Inhibits Cell Migration. Int J Mol Sci. 2017 May 3;18(5). pii: E971. doi: 10.3390/ijms18050971. PubMed PMID: 28467385; PubMed Central PMCID: PMC5454884.
4: Li L, Jiang S, Li X, Liu Y, Su J, Chen J. Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site. Eur J Med Chem. 2018 May 10;151:482-494. doi: 10.1016/j.ejmech.2018.04.011. Epub 2018 Apr 5. Review. PubMed PMID: 29649743.
5: Kumar B, Kumar R, Skvortsova I, Kumar V. Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials. Curr Cancer Drug Targets. 2017;17(4):357-375. doi: 10.2174/1568009616666160928110818. Review. PubMed PMID: 27697026.
6: Churchill CD, Klobukowski M, Tuszynski JA. Analysis of the binding mode of laulimalide to microtubules: Establishing a laulimalide-tubulin pharmacophore. J Biomol Struct Dyn. 2016 Jul;34(7):1455-69. doi: 10.1080/07391102.2015.1078115. Epub 2016 Apr 28. PubMed PMID: 26230757.
7: Kanakkanthara A, Rowe MR, Field JJ, Northcote PT, Teesdale-Spittle PH, Miller JH. βI-tubulin mutations in the laulimalide/peloruside binding site mediate drug sensitivity by altering drug-tubulin interactions and microtubule stability. Cancer Lett. 2015 Sep 1;365(2):251-60. doi: 10.1016/j.canlet.2015.06.001. Epub 2015 Jun 4. PubMed PMID: 26052091.
8: Churchill CD, Klobukowski M, Tuszynski JA. The Unique Binding Mode of Laulimalide to Two Tubulin Protofilaments. Chem Biol Drug Des. 2015 Aug;86(2):190-9. doi: 10.1111/cbdd.12475. Epub 2014 Nov 28. PubMed PMID: 25376845.
9: Yu EC, Johnson BM, Townsend EM, Schrock RR, Hoveyda AH. Synthesis of Linear (Z)-α,β-Unsaturated Esters by Catalytic Cross-Metathesis. The Influence of Acetonitrile. Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13210-13214. doi: 10.1002/anie.201608087. PubMed PMID: 27634213; PubMed Central PMCID: PMC5169164.
