leptomycin

{{chembox

| Name = Leptomycin B

| Watchedfields = changed

| verifiedrevid = 450847443

| ImageFile=Leptomycin B.svg

| ImageSize=

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

| OtherNames=

|Section1={{Chembox Identifiers

| InChI = 1/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

| InChIKey = YACHGFWEQXFSBS-RJXCBBHPBE

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = YACHGFWEQXFSBS-RJXCBBHPSA-N

| CASNo_Ref = {{cascite|correct|??}}

| CASNo=87081-35-4

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Y031I2N1EO

| PubChem=6917907

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID=21106330

| SMILES = OC(=O)\C=C(/C)C[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)/C=C(\C)/C=C/C[C@@H](C)\C=C(/CC)\C=C\[C@@H]1OC(=O)/C=C\[C@@H]1C

}}

|Section2={{Chembox Properties

| C=33 | H=48 | O=6

| MolarMass=

| Appearance=

| Density=1.072 g/mL

| MeltingPt=

| BoilingPt=

| Solubility=

}}

|Section3={{Chembox Hazards

| MainHazards=

| FlashPt=

| AutoignitionPt =

}}

}}

Leptomycins are secondary metabolites produced by Streptomyces spp.

Leptomycin B (LMB) was originally discovered as a potent antifungal compound. {{cite journal |vauthors=Hamamoto T, Seto H, Beppu T |title=Leptomycins A and B, new antifungal antibiotics. II. Structure elucidation |journal=J. Antibiot. |volume=36 |issue=6 |pages=646–50 |year=1983 |pmid=6874586 |doi=10.7164/antibiotics.36.646|doi-access=free }} Leptomycin B was found to cause cell elongation of the fission yeast Schizosaccharomyces pombe. Since then this elongation effect has been used for the bioassay of leptomycin. However, recent data shows that leptomycin causes G1 cell cycle arrest in mammalian cells and is a potent anti-tumor agent against murine experimental tumors in combination therapy.{{cite journal |last=Lu |first=Chuanwen |author2=Changxia Shao |author3=Everardo Cobos |author4=Kamaleshwar P. Singh |author5=Weimin Gao |date=March 2012 |title=Chemotherapeutic Sensitization of Leptomycin B Resistant Lung Cancer Cells by Pretreatment with Doxorubicin |journal=PLOS ONE |volume=7 |issue=3 |pages=e32895 |location = United States| issn = 1932-6203 | pmid =22412944 |pmc=3296751 |doi = 10.1371/journal.pone.0032895 | bibcode =2012PLoSO...732895L |doi-access=free }}

Leptomycin B has been shown to be a potent and specific nuclear export inhibitor in humans{{cite journal |vauthors=Kudo N, Wolff B, Sekimoto T, etal |title=Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1 |journal=Exp. Cell Res. |volume=242 |issue=2 |pages=540–7 |date=August 1998 |pmid=9683540 |doi=10.1006/excr.1998.4136 }} and the fission yeast S. pombe.{{cite journal |vauthors=Nishi K, Yoshida M, Fujiwara D, Nishikawa M, Horinouchi S, Beppu T |title=Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression |journal=J. Biol. Chem. |volume=269 |issue=9 |pages=6320–4 |date=March 1994 |doi=10.1016/S0021-9258(17)37374-X |pmid=8119981 |url=http://www.jbc.org/content/269/9/6320.abstract|doi-access=free }} Leptomycin B alkylates and inhibits CRM1 (chromosomal region maintenance)/exportin 1 ({{Gene|XPO1}}), a protein required for nuclear export of proteins containing a nuclear export sequence (NES), by glycosylating a cysteine residue (cysteine 529 in S. pombe).{{cite journal |vauthors=Kudo N, Matsumori N, Taoka H, etal |title=Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=16 |pages=9112–7 |date=August 1999 |pmid=10430904 |pmc=17741 |doi= 10.1073/pnas.96.16.9112|bibcode=1999PNAS...96.9112K |doi-access=free }} In addition to antifungal and antibacterial activities, leptomycin B blocks the cell cycle and is a potent anti-tumor agent. At low nM concentrations, leptomycin B blocks the nuclear export of many proteins including HIV-1 Rev, MAPK/ERK, and NF-κB/IκB, and it inhibits the inactivation of p53.{{cite journal|vauthors=Hietanen S, Lain S, Krausz E, Blattner C, Lane DP | title=Activation of p53 in cervical carcinoma cells by small molecules. | journal=Proc Natl Acad Sci U S A | year= 2000 | volume= 97 | issue= 15 | pages= 8501–6 | pmid=10900010 | doi= 10.1073/pnas.97.15.8501| pmc=26977 | bibcode=2000PNAS...97.8501H | doi-access=free }} Leptomycin B also inhibits the export and translation of many RNAs, including COX-2 and c-Fos mRNAs, by inhibiting the export of ribonucleoproteins.{{Citation needed|date=November 2010}}

Leptomycin A (LPA) was discovered together with LMB. LMB is twice as potent as LPA.{{clarify|reason=Potency in terms of which of the several biological assays described above?|date=November 2016}}