Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay

PAUL STEAD; SHAZIA LATIF; ANDREW P. BLACKABY; PHILIP J. SIDEBOTTOM; ANGELA DEAKIN; NICHOLAS L. TAYLOR; PAUL LIFE; JOHN SPAULL; FIONA BURRELL; ROSIE JONES; JANE LEWIS; IAN DAVIDSON; THOMAS MANDER

doi:10.7164/antibiotics.53.657

PAUL STEAD, SHAZIA LATIF, ANDREW P. BLACKABY, PHILIP J. SIDEBOTTOM, ANGELA DEAKIN, NICHOLAS L. TAYLOR, PAUL LIFE, JOHN SPAULL, FIONA BURRELL, ROSIE JONES, JANE LEWIS, IAN DAVIDSON, THOMAS MANDER

Author information

PAUL STEAD
Glaxo Wellcome Medicines Research Centre
SHAZIA LATIF
Glaxo Wellcome Medicines Research Centre
ANDREW P. BLACKABY
Glaxo Wellcome Medicines Research Centre
PHILIP J. SIDEBOTTOM
Glaxo Wellcome Medicines Research Centre
ANGELA DEAKIN
Glaxo Wellcome Medicines Research Centre
NICHOLAS L. TAYLOR
Glaxo Wellcome Medicines Research Centre
PAUL LIFE
Glaxo Wellcome Medicines Research Centre
JOHN SPAULL
Glaxo Wellcome Medicines Research Centre
FIONA BURRELL
Glaxo Wellcome Medicines Research Centre
ROSIE JONES
Glaxo Wellcome Medicines Research Centre
JANE LEWIS
Glaxo Wellcome Medicines Research Centre
IAN DAVIDSON
Glaxo Wellcome Medicines Research Centre
THOMAS MANDER
Glaxo Wellcome Medicines Research Centre

JOURNAL FREE ACCESS

2000 Volume 53 Issue 7 Pages 657-663

DOI https://doi.org/10.7164/antibiotics.53.657

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Abstract

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.

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