Discovery of novel ansamycins possessing potent inhibitory activity in a cell-based oncostatin M signalling assay.
We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties.
Stead
P
P
GlaxoWellcome Medicines Research Centre, Stevenage, Herts, UK.
Latif
S
S
Blackaby
A P
AP
Sidebottom
P J
PJ
Deakin
A
A
Taylor
N L
NL
Life
P
P
Spaull
J
J
Burrell
F
F
Jones
R
R
Lewis
J
J
Davidson
I
I
Mander
T
T
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016227:Benzoquinones; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008168:Lung / Q000166:cytology / Q000187:drug effects; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011809:Quinones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017828:Rifabutin / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction; D013302:Streptomyces / Q000378:metabolism
C414126:19-demethoxylebstatin; D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D015850:Interleukin-6; D047029:Lactams, Macrocyclic; C508351:OSM protein, human; D010455:Peptides; D011506:Proteins; D011809:Quinones; D011994:Recombinant Proteins; C414123:reblastatin; D053683:Oncostatin M; D017828:Rifabutin; D000469:Alkaline Phosphatase; C001277:geldanamycin