Leptomycin B | CAS#87081-35-4 | CRM1 inhibitor

MedKoo Cat#: 330114 | Name: Leptomycin B

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Leptomycin B is a potent inhibitor of the nuclear export of proteins. It directly blocks the interaction of CRM1 (exportin 1) with nuclear export signals (NES), preventing the export of a broad range of proteins. Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells.

Chemical Structure

Leptomycin B

CAS#87081-35-4

Theoretical Analysis

MedKoo Cat#: 330114

Name: Leptomycin B

CAS#: 87081-35-4

Chemical Formula: C33H48O6

Exact Mass: 540.3451

Molecular Weight: 540.74

Elemental Analysis: C, 73.30; H, 8.95; O, 17.75

Price and Availability

Size	Price	Availability
25mg	USD 1,450.00	2 Weeks
50mg	USD 2,250.00	2 Weeks
100mg	USD 3,650.00	2 Weeks
200mg	USD 6,150.00	2 Weeks

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Synonym

Leptomycin B; Elactocin; LMB; Mantuamycin; NSC 364372;

IUPAC/Chemical Name

19-[(2S,3S)-3,6-dihydro-3-methyl-6-oxo-2H-pyran-2-yl]-17-ethyl-6-hydroxy-3,5S,7S,9R,11,15R,hexamethyl-8-oxo-2E,10E,12E,16Z,18E-nonadecapentaenoic acid

InChi Key

YACHGFWEQXFSBS-MUWQPLQNSA-N

InChi Code

InChI=1S/C33H48O6/c1-9-28(14-15-29-24(5)13-16-31(36)39-29)19-22(3)12-10-11-21(2)17-25(6)32(37)27(8)33(38)26(7)18-23(4)20-30(34)35/h10-11,13-17,19-20,22,24-27,29,33,38H,9,12,18H2,1-8H3,(H,34,35)/b11-10+,15-14+,21-17+,23-20+,28-19-/t22-,24+,25-,26+,27-,29+,33?/m1/s1

SMILES Code

O=C(O)/C=C(C)/C[C@H](C)C(O)[C@H](C)C([C@H](C)/C=C(C)/C=C/C[C@@H](C)/C=C(CC)\C=C\[C@H]1[C@@H](C)C=CC(O1)=O)=O

Appearance

Solid powder

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

>2 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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Leptomycin B (CI 940; LMB) is a potent inhibitor of the nuclear export of proteins.

In vitro activity:

Leptomycin B (LMB), a specific inhibitor of the nuclear export factor CRM1 potently inhibits the stabilization of COX-2 mRNA in MDA-MB-231 human mammary cancer cells. LMB suppressed COX-2 expression by interleukin-1beta in HT-29 human colon cancer cells and in human umbilical vein endothelial cells but had no effect on COX-2 expression induced by Escherichia coli lipopolysaccharide in monocytic THP-1 cells. Reference: J Biol Chem. 2003 Jan 31;278(5):2773-6. https://pubmed.ncbi.nlm.nih.gov/12468543/

In vivo activity:

Leptomycin B (LMB, an inhibitor of chromosome region maintenance 1) attenuated SE-induced vasogenic edema formation in rats. This anti-edema effect of LMB was relevant to inhibitions of VEGF over-expression as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. Reference: Brain Res. 2016 Nov 15;1651:27-35. https://pubmed.ncbi.nlm.nih.gov/27659963/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	184.93
	Ethanol	75.0	138.70

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 540.74 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. Jang BC, Muñoz-Najar U, Paik JH, Claffey K, Yoshida M, Hla T. Leptomycin B, an inhibitor of the nuclear export receptor CRM1, inhibits COX-2 expression. J Biol Chem. 2003 Jan 31;278(5):2773-6. doi: 10.1074/jbc.C200620200. Epub 2002 Dec 4. PMID: 12468543. 2. Freedman DA, Levine AJ. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol. 1998 Dec;18(12):7288-93. doi: 10.1128/MCB.18.12.7288. PMID: 9819415; PMCID: PMC109310. 3. Kim DS, Min SJ, Kim MJ, Kim JE, Kang TC. Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19. PMID: 27659963. 4. Kobayashi T, Shinkai H. Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation. J Invest Dermatol. 2005 Feb;124(2):331-7. doi: 10.1111/j.0022-202X.2004.23595.x. PMID: 15675951.

In vitro protocol:

In vivo protocol:

1. Kim DS, Min SJ, Kim MJ, Kim JE, Kang TC. Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19. PMID: 27659963. 2. Kobayashi T, Shinkai H. Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation. J Invest Dermatol. 2005 Feb;124(2):331-7. doi: 10.1111/j.0022-202X.2004.23595.x. PMID: 15675951.

1: Thirumalairaj J, Sivasankari K, Natarajaseenivasan K, Balagurunathan R. Potential anti-leptospiral compound, leptomycin B from marine Streptomyces indiaensis MSU5: taxonomy, fermentation, compound isolation, in vitro and in vivo efficacy. World J Microbiol Biotechnol. 2017 Sep 27;33(10):187. doi: 10.1007/s11274-017-2351-1. PubMed PMID: 28956236. 2: Liu Z, Gao W. Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21. PubMed PMID: 28942004; PubMed Central PMCID: PMC5643250. 3: Min SJ, Hyun HW, Kang TC. Leptomycin B attenuates neuronal death via PKA- and PP2B-mediated ERK1/2 activation in the rat hippocampus following status epilepticus. Brain Res. 2017 Sep 1;1670:14-23. doi: 10.1016/j.brainres.2017.06.002. Epub 2017 Jun 7. PubMed PMID: 28601633. 4: Rahmani K, Dean DA. Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1). Biochem Biophys Res Commun. 2017 Jun 24;488(2):253-258. doi: 10.1016/j.bbrc.2017.04.042. Epub 2017 Apr 12. PubMed PMID: 28412356; PubMed Central PMCID: PMC5551409. 5: Kim DS, Min SJ, Kim MJ, Kim JE, Kang TC. Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19. PubMed PMID: 27659963. 6: Yin F, Sun P, Tang B, Gong H, Ke Q, Li A. Anti-parasitic effects of Leptomycin B isolated from Streptomyces sp. CJK17 on marine fish ciliate Cryptocaryon irritans. Vet Parasitol. 2016 Feb 15;217:89-94. doi: 10.1016/j.vetpar.2015.12.034. Epub 2016 Jan 4. PubMed PMID: 26827867. 7: Cromie MM, Gao W. Epigallocatechin-3-gallate enhances the therapeutic effects of leptomycin B on human lung cancer a549 cells. Oxid Med Cell Longev. 2015;2015:217304. doi: 10.1155/2015/217304. Epub 2015 Apr 1. PubMed PMID: 25922640; PubMed Central PMCID: PMC4397486. 8: Park D, Lengyel J, Rice SA. Role of immediate early protein ICP27 in the differential sensitivity of herpes simplex viruses 1 and 2 to leptomycin B. J Virol. 2013 Aug;87(16):8940-51. doi: 10.1128/JVI.00633-13. Epub 2013 Jun 5. PubMed PMID: 23740995; PubMed Central PMCID: PMC3754045. 9: Sun Q, Carrasco YP, Hu Y, Guo X, Mirzaei H, Macmillan J, Chook YM. Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1303-8. doi: 10.1073/pnas.1217203110. Epub 2013 Jan 7. PubMed PMID: 23297231; PubMed Central PMCID: PMC3557022. 10: Lu C, Shao C, Cobos E, Singh KP, Gao W. Chemotherapeutic sensitization of leptomycin B resistant lung cancer cells by pretreatment with doxorubicin. PLoS One. 2012;7(3):e32895. doi: 10.1371/journal.pone.0032895. Epub 2012 Mar 7. PubMed PMID: 22412944; PubMed Central PMCID: PMC3296751. 11: Kobayashi T. Anti-inflammatory treatment for contact dermatitis by topical leptomycin B: inhibitory effects on the induced expression of matrix metalloproteinases (MMP)-9 and -3. Eur J Dermatol. 2011 May-Jun;21(3):438-9. doi: 10.1684/ejd.2011.1336. PubMed PMID: 21527372. 12: Shao C, Lu C, Chen L, Koty PP, Cobos E, Gao W. p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma. Cancer Chemother Pharmacol. 2011 Jun;67(6):1369-80. doi: 10.1007/s00280-010-1434-6. Epub 2010 Aug 28. PubMed PMID: 20803015. 13: Jolly CE, Gray LJ, Parish JL, Lain S, Herrington CS. Leptomycin B induces apoptosis in cells containing the whole HPV 16 genome. Int J Oncol. 2009 Sep;35(3):649-56. PubMed PMID: 19639186. 14: Allan EK, Hamilton A, Hatziieremia S, Zhou P, Jørgensen HG, Vigneri P, Holyoake TL. Nuclear entrapment of BCR-ABL by combining imatinib mesylate with leptomycin B does not eliminate CD34+ chronic myeloid leukaemia cells. Leukemia. 2009 May;23(5):1006-8. doi: 10.1038/leu.2008.367. Epub 2009 Jan 8. PubMed PMID: 19151780. 15: Hoshino I, Matsubara H, Komatsu A, Akutsu Y, Nishimori T, Yoneyama Y, Murakami K, Sakata H, Matsushita K, Miyazawa Y, Brooks R, Yoshida M, Ochiai T. Combined effects of p53 gene therapy and leptomycin B in human esophageal squamous cell carcinoma. Oncology. 2008;75(1-2):113-9. doi: 10.1159/000155212. Epub 2008 Sep 11. PubMed PMID: 18784437. 16: Kancha RK, von Bubnoff N, Miething C, Peschel C, Götze KS, Duyster J. Imatinib and leptomycin B are effective in overcoming imatinib-resistance due to Bcr-Abl amplification and clonal evolution but not due to Bcr-Abl kinase domain mutation. Haematologica. 2008 Nov;93(11):1718-22. doi: 10.3324/haematol.13207. Epub 2008 Aug 25. PubMed PMID: 18728023. 17: Muro E, Hoang TQ, Jobart-Malfait A, Hernandez-Verdun D. In nucleoli, the steady state of nucleolar proteins is leptomycin B-sensitive. Biol Cell. 2008 May;100(5):303-13. PubMed PMID: 18052928. 18: Gray LJ, Bjelogrlic P, Appleyard VC, Thompson AM, Jolly CE, Lain S, Herrington CS. Selective induction of apoptosis by leptomycin B in keratinocytes expressing HPV oncogenes. Int J Cancer. 2007 Jun 1;120(11):2317-24. PubMed PMID: 17290384. 19: Jackson RS 2nd, Cho YJ, Stein S, Liang P. CYFIP2, a direct p53 target, is leptomycin-B sensitive. Cell Cycle. 2007 Jan 1;6(1):95-103. Epub 2007 Jan 29. PubMed PMID: 17245118. 20: Jang BC, Sung SH, Park JG, Park JW, Suh MH, Choi IH, Yoshida M, Yoo SK, Suh SI. Leptomycin B, a metabolite of Streptomyces, inhibits the expression of inducible nitric oxide synthase in BV2 microglial cells. Int J Oncol. 2006 Dec;29(6):1509-15. PubMed PMID: 17088990.