Affiliation: Institute of Cancer Research
Rye C, Chessum N, Lamont S, Pike K, Faulder P, Demeritt J, et al
. Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9. Medchemcomm. 2016;7:1580-1586 pubmed
..00 ?M). Optimisation of cellular SAR led to an inhibitor with improved potency (25, 15 nM) in the HSF1 phenotypic assay. The 4,6-pyrimidine 25 was also shown to have high potency against the CDK9 enzyme (3 nM). ..
Workman P, Burrows F, Neckers L, Rosen N. Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci. 2007;1113:202-16 pubmed
..We stress how basic and translational research has been mutually beneficial and indicate future directions to enhance our understanding of molecular chaperones and their exploitation in cancer and other diseases. ..
Blagg J, Workman P. Chemical biology approaches to target validation in cancer. Curr Opin Pharmacol. 2014;17:87-100 pubmed publisher
..Among other topical examples, we highlight the emergence of designed irreversible chemical tools to study potential target proteins and oncogenic pathways that were hitherto regarded as poorly druggable. ..
Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med. 2004;10:47-51 pubmed
..However, the reason for therapeutic selectivity in cancer cells versus normal cells is unclear. New research now shows that Hsp90 exists in cancer cells in a heightened, activated state that is highly susceptible to inhibition by 17AAG. ..
Workman P. Overview: translating Hsp90 biology into Hsp90 drugs. Curr Cancer Drug Targets. 2003;3:297-300 pubmed
..The opportunities and challenges involved in translating the fast moving biology of Hsp90 into patient benefit is discussed. ..
Workman P. Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Lett. 2004;206:149-57 pubmed
..This article reviews the current status and future prospects for the exploitation of Hsp90 as a new molecular target for cancer treatment. ..
Banerji U, Judson I, Workman P. The clinical applications of heat shock protein inhibitors in cancer - present and future. Curr Cancer Drug Targets. 2003;3:385-90 pubmed
..Examples of likely disease targets include chronic myeloid leukaemia, melanoma, breast, ovarian, brain, thyroid, colorectal and prostate cancer. ..
Yap T, Bjerke L, Clarke P, Workman P. Drugging PI3K in cancer: refining targets and therapeutic strategies. Curr Opin Pharmacol. 2015;23:98-107 pubmed publisher
..Finally, we envision the future development and use of PI3K inhibitors for the treatment of patients with a range of malignancies. ..
Workman P, Clarke P, Raynaud F, Van Montfort R. Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res. 2010;70:2146-57 pubmed publisher
..The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery. ..