"Human malignant pleural mesothelioma is an aggressive (fatal) lung cancer which is always associated with previous asbestos exposure. Typically symptoms do not appear until 35-40 years after the original exposure, with life expectancy then 12-18 months. Given the great use of asbestos during the 20th century (before its long overdue ban in 1985) and this long latency period, it is no surprise that cases of mesothelioma continue to rise. There is no known cure for mesothelioma: traditional chemotherapeutic cancer treatments have had little impact on the disease and radiotherapy or partial pleurectomy have only very limited impact on life expectancy. However, very little in the way of mesothelioma research is taking place, as it is frequently not considered to be a ‘big enough market’ (<1% of all cancers in the U.K.) and consequently there are currently no drugs in development for this disease. A second reason for this is that there have been no reported good lead compounds (natural products) as a starting point for the drug discovery process. Until now.
First isolated from Streptomyces sp. AK-AB27 in 2008, JBIR-23 possesses a unique structural architecture, hitherto unobserved in Streptomyces extracts. Furthermore, JBIR-23 is unique, in that it is the first natural product to be isolated to exhibit activity against human malignant pleural mesothelioma. This is an amazing breakthrough: the isolation of the first natural product to be highly active against mesothelioma is crucial, providing a precious lead compound for investigation.
The aim of the project, therefore, is to investigate the synthesis and anti-mesothelioma activity of JBIR-23 and to prepare further analogues to commence structure-activity studies. This will be the first study of this kind."
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