87081-35-4

Basic information

• Product Name: LEPTOMYCIN B FROM STREPTOMYCES SP
• Synonyms: LEPTOMYCIN B FROM STREPTOMYCES SP;2,10,12,16,18-nonadecapentanoicacid,19-(3,6-dihydro-3-methyl-6-oxo-2h-pyran-2;7,9,11,15-hexamethyl-8-oxo--yl)-17-ethyl-6-hydroxy-5;antibioticci940;antibioticcl1957a;CI-940, Elactocin, PD 114720, ATS 1287B, Mantuamycin, 19-(3,6-dihydro-3-methyl-6-oxo-2H-pyran-2-yl)-17-ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-8-oxo-2,10,12,16,18-Nonadecapentaenoic acid;(2E,10Z,12E,16Z,18E)-17-ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-19-(3-methyl-6-oxo-2,3-dihydropyran-2-yl)-8-oxo-nonadeca-2,10,12,16,18-pentaenoic acid;2,10,12,16,18-Nonadecapentaenoic acid, 19-(3,6-dihydro-3-methyl-6-oxo-2H-pyran-2-yl)-17-ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-8-oxo-
• CAS NO: 87081-35-4
• Molecular Formula: C33H48O6
• Molecular Weight: 540.736
• EINECS: 617-954-4
• Product Categories: Antifungal;antibiotic
• Mol File: 87081-35-4.mol
• Article Data: 1

Chemical Properties

• Melting Point: 41-44°, with prior softening (Hokanson)
• Boiling Point: 725.8 °C at 760 mmHg
• Flash Point: 11°(52°F)
• Appearance: White crystalline solid.
• Density: 1.072 g/cm³
• Vapor Pressure: 2.53E-24mmHg at 25°C
• Refractive Index: 1.542
• Storage Temp.: −20°C
• Solubility: Supplied in solution in ethanol (1 mg/ml). Further dilutions may be made with either ethanol or DMSO.
• Stability: Stable for 1 year from date of purchase as supplied. Solutions or dilutions in DMSO are not stable. Solutions should be made fresh and used within one working day.
• CAS DataBase Reference: LEPTOMYCIN B FROM STREPTOMYCES SP(CAS DataBase Reference)
• NIST Chemistry Reference: LEPTOMYCIN B FROM STREPTOMYCES SP(87081-35-4)
• EPA Substance Registry System: LEPTOMYCIN B FROM STREPTOMYCES SP(87081-35-4)

Safety Data

• Hazard Codes: F,T
• Statements: 23/25-36/38-39/23/24/25-23/24/25-11
• Safety Statements: 7-16-24-33-45-36/37
• RIDADR: UN 1230 3/PG 2
• WGK Germany: 3
• HazardClass: 3
• Hazardous Substances Data: 87081-35-4(Hazardous Substances Data)

Usage

Description

Leptomycin B (87081-35-4) is an inhibitor of nuclear export of proteins. Acts via covalent binding to and inhibiting CRM1/exportin-1.1 Inhibits the nuclear export of the HIV regulatory protein Rev.2 Leptomycin B stabilizes p53 by blocking its nuclear export.3

Uses

Different sources of media describe the Uses of 87081-35-4 differently. You can refer to the following data:
1. Leptomycin B is the dominant and most studied member of the leptomycin class, isolated from selected Streptomyces strains. Leptomycin B is a nanomolar active and specific nuclear export inhibitor. Its target is CRM1/exportin1, a protein in the nuclear export sequence (NES). Proteins affected include c-Abl, cyclin B1, HIV-1 Rev, IκB, MPF, MAP/ERK, MDM2/p53, NF-κB/IκB7 and PKA. Leptomycin B inhibits export of many RNAs, e.g. COX-2 and c-FOS mRNA. Leptomycin B also shows antifungal and antibacterial and potent antitumour activities.
2. Biological tool for studying nuclear localization and protein trafficking in eukaryotic cells.
3. Potent, specific inhibitor of nuclear export signal (NES)-dependent protein export from the nucleus

Definition

ChEBI: A leptomycin having a (2E,10E,12E,16Z,18E)-double bond configuration as well as an ethyl substituent at position 17.

General Description

Leptomycin B is an anti-fungal antibiotic, anti-tumor cytotoxin that inhibits CRM1-dependent, NES-dependent nucleo-cytoplasmic translocation (nuclear export inhibitor). NES containing proteins include HIV-1 REV; actin, c-Abl, cyclin B1, MDM2/p53, I?B, MPF, PKA and MEK.

Biological Activity

Antifungal antibiotic that is an inhibitor of the nuclear export of proteins; acts by binding directly to and inhibiting CRM1/exportin-1. Inhibits the nuclear export of the HIV regulatory protein Rev and stabilizes p53. Antitumor in vitro and in vivo .

Biochem/physiol Actions

Leptomycin B is an unsaturated, branched-chain fatty acid, and is an important tool in the study of nuclear export. Leptomycin B is a specific inhibitor of proteins containing nuclear export signal. Leptomycin B inhibits nucleo-cytoplasmic translocation of molecules such as the HIV-1 Rev protein and Rev-dependent export of mRNA. The addition of very small amounts to fibroblasts causes accumulation of MEK in the nucleus. Other proteins that are influenced by leptomycin?B are actin, c-Abl, cyclin B1, MDM2/p53, IκB, MPF, and PKA. The suggested inhibition mechanism involves the direct binding of leptomycin?B to CRM1, which blocks the binding of CRM1 to proteins containing the nuclear export signal, via the interaction with cysteine residue in CRM1 control conserved region.

References

1) Kudo et al. (1998), Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1; Exp. Cell Res., 242 540 2) Wolff et al. (1997), Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA; Chem. Biol., 4 139 3) Freedman and Levine (1998), Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6; Mol. Cell. Biol., 18 7288

InChI: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

Upstream product

• 217640-21-6 (5S,6S)-6-[(1E,3Z,7E,9E,17E)-(5R,11R,12S,13R,14R,15S)-14,19-Bis-(tert-butyl-dimethyl-silanyloxy)-3-ethyl-12-hydroxy-5,9,11,13,15,17-hexamethyl-nonadeca-1,3,7,9,17-pentaenyl]-5-methyl-5,6-dihydro-pyran-2-one 
• 217640-23-8 (5S,6S)-6-((1E,3Z,7E,9E,17E)-(5R,11R,13S,14R,15S)-3-Ethyl-14,19-dihydroxy-5,9,11,13,15,17-hexamethyl-12-oxo-nonadeca-1,3,7,9,17-pentaenyl)-5-methyl-5,6-dihydro-pyran-2-one 
• 217640-15-8 (S)-3-[(E)-(2S,3R,4R,5R,6S)-5-(tert-Butyl-dimethyl-silanyloxy)-3-hydroxy-10-methoxymethoxy-2,4,6,8-tetramethyl-dec-8-enoyl]-4-isopropyl-oxazolidin-2-one 
• 217640-19-2 (2E,10E)-(4R,5S,6R,7R,8S)-1-Bromo-7,12-bis-(tert-butyl-dimethyl-silanyloxy)-2,4,6,8,10-pentamethyl-dodeca-2,10-dien-5-ol 
• 217640-18-1 (2E,10E)-(4R,5S,6R,7R,8S)-1-Bromo-7-(tert-butyl-dimethyl-silanyloxy)-12-methoxymethoxy-2,4,6,8,10-pentamethyl-dodeca-2,10-dien-5-ol 
• 217640-17-0 (2E,10E)-(4R,5S,6R,7R,8S)-7-(tert-Butyl-dimethyl-silanyloxy)-12-methoxymethoxy-2,4,6,8,10-pentamethyl-dodeca-2,10-diene-1,5-diol 
• 217640-08-9 (2S,3S)-2-[(1E,3Z)-(R)-3-Ethyl-7-(4-methoxy-benzyloxy)-5-methyl-hepta-1,3-dienyl]-6-isopropoxy-3-methyl-3,6-dihydro-2H-pyran 
• 217640-13-6 (S)-3-((E)-(2S,3R,4S)-3-Hydroxy-8-methoxymethoxy-2,4,6-trimethyl-oct-6-enoyl)-4-isopropyl-oxazolidin-2-one 
• 217640-26-1 (5S,6S)-6-[(1E,3Z)-(R)-3-Ethyl-7-(4-methoxy-benzyloxy)-5-methyl-hepta-1,3-dienyl]-5-methyl-5,6-dihydro-pyran-2-one 
• 217640-14-7 (E)-(2S,3R,4S)-3-(tert-Butyl-dimethyl-silanyloxy)-8-methoxymethoxy-2,4,6-trimethyl-oct-6-enal 
• 217640-11-4 (S)-4-Isopropyl-3-((E)-(S)-6-methoxymethoxy-2,4-dimethyl-hex-4-enoyl)-oxazolidin-2-one 
• 217640-27-2 (5S,6S)-6-((1E,3Z)-(R)-3-Ethyl-7-hydroxy-5-methyl-hepta-1,3-dienyl)-5-methyl-5,6-dihydro-pyran-2-one 
• 217640-09-0 (4Z,6E)-(R)-5-Ethyl-3-methyl-7-((2S,3S)-3-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)-hepta-4,6-dienal 

Relevant articles and documents

Absolute stereostructure and total synthesis of leptomycin B

The absolute stereostructure of leptomycin B, an antitumor antibiotic and inhibitor of nuclear protein export, was firstly presumed as 1 having 4S, 5R, 10R, 16R, 18S, 19R, 20S on the basis of NMR comparison with callystatin A (2) and then 1 was asymmetric