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Professor Paul Workman, Signal Transduction & Molecular Pharmacology and Clinical Pharmacology & Trials 

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Journal Articles

Ferraldeschi, R., Welti, J., Powers, M.V., Yuan, W., Smyth, T., Seed, G., Riisnaes, R., Hedayat, S., Wang, H., Crespo, M., et al. (2016). Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. Cancer research, Vol.76 (9), pp. 2731-2742.

Ang, J.E., Pandher, R., Ang, J.C., Asad, Y.J., Henley, A.T., Valenti, M., Box, G., de Haven Brandon, A., Baird, R.D., Friedman, L., et al. (2016). Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation. Molecular cancer therapeutics, Vol.15 (6), pp. 1412-1424.

Mallinger, A., Schiemann, K., Rink, C., Stieber, F., Calderini, M., Crumpler, S., Stubbs, M., Adeniji-Popoola, O., Poeschke, O., Busch, M., et al. (2016). Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. Journal of medicinal chemistry, Vol.59 (3), pp. 1078-1101.

Cheeseman, M.D., Westwood, I.M., Barbeau, O., Rowlands, M., Dobson, S., Jones, A.M., Jeganathan, F., Burke, R., Kadi, N., Workman, P., et al. (2016). Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70. J med chem, Vol.59 (10), pp. 4625-4636.  show abstract

Sarker, D., Ang, J.E., Baird, R., Kristeleit, R., Shah, K., Moreno, V., Clarke, P.A., Raynaud, F.I., Levy, G., Ware, J.A., et al. (2015). First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin cancer res, Vol.21 (1), pp. 77-86.  show abstract

Smith, J.R., de Billy, E., Hobbs, S., Powers, M., Prodromou, C., Pearl, L., Clarke, P.A. & Workman, P. (2015). Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins. Oncogene, Vol.34 (1), pp. 15-26.  show abstract

Dale, T., Clarke, P.A., Esdar, C., Waalboer, D., Adeniji-Popoola, O., Ortiz-Ruiz, M.-., Mallinger, A., Samant, R.S., Czodrowski, P., Musil, D., et al. (2015). A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nature chemical biology, Vol.11 (12), pp. 973-980.

Gurden, M.D., Westwood, I.M., Faisal, A., Naud, S., Cheung, K.-., McAndrew, C., Wood, A., Schmitt, J., Boxall, K., Mak, G., et al. (2015). Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. Cancer research, Vol.75 (16), pp. 3340-3354.

Mallinger, A., Crumpler, S., Pichowicz, M., Waalboer, D., Stubbs, M., Adeniji-Popoola, O., Wood, B., Smith, E., Thai, C., Henley, A.T., et al. (2015). Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J med chem, Vol.58 (4), pp. 1717-1735.  show abstract

Mitsopoulos, C., Schierz, A.C., Workman, P. & Al-Lazikani, B. (2015). Distinctive Behaviors of Druggable Proteins in Cellular Networks. Plos computational biology, Vol.11.

Samant, R.S., Clarke, P.A. & Workman, P. (2014). E3 ubiquitin ligase Cullin-5 modulates multiple molecular and cellular responses to heat shock protein 90 inhibition in human cancer cells. Proc natl acad sci u s a, Vol.111 (18), pp. 6834-6839.  show abstract

Workman, P. (2014). Successes for UK cancer partnership. Nature, Vol.510 (7504), pp. 218-218.

Patel, M.N., Halling-Brown, M.D., Tym, J.E., Workman, P. & Al-Lazikani, B. (2013). Objective assessment of cancer genes for drug discovery. Nat rev drug discov, Vol.12 (1), pp. 35-50.  show abstract

Polier, S., Samant, R.S., Clarke, P.A., Workman, P., Prodromou, C. & Pearl, L.H. (2013). ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system. Nat chem biol, Vol.9 (5), pp. 307-312.  show abstract

Bjerke, L., Mackay, A., Nandhabalan, M., Burford, A., Jury, A., Popov, S., Bax, D.A., Carvalho, D., Taylor, K.R., Vinci, M., et al. (2013). Histone H3 3 Mutations Drive Pediatric Glioblastoma through Upregulation of MYCN. Cancer discovery, Vol.3 (5), pp. 512-519.

Workman, P. & Al-Lazikani, B. (2013). Drugging cancer genomes. Nat rev drug discov, Vol.12 (12), pp. 889-890.

Al-Lazikani, B., Banerji, U. & Workman, P. (2012). Combinatorial drug therapy for cancer in the post-genomic era. Nat biotechnol, Vol.30 (7), pp. 679-692.  show abstract

Yap, T.A., Walton, M.I., Grimshaw, K.M., Te Poele, R.H., Eve, P.D., Valenti, M.R., de Haven Brandon, A.K., Martins, V., Zetterlund, A., Heaton, S.P., et al. (2012). AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity. Clin cancer res, Vol.18 (14), pp. 3912-3923.  show abstract

Day, J.E., Sharp, S.Y., Rowlands, M.G., Aherne, W., Hayes, A., Raynaud, F.I., Lewis, W., Roe, S.M., Prodromou, C., Pearl, L.H., et al. (2011). Targeting the Hsp90 Molecular Chaperone with Novel Macrolactams Synthesis, Structural, Binding, and Cellular Studies. Acs chemical biology, Vol.6 (12), pp. 1339-1347.

Rowlands, M., McAndrew, C., Prodromou, C., Pearl, L., Kalusa, A., Jones, K., Workman, P. & Aherne, W. (2010). Detection of the ATPase activity of the molecular chaperones Hsp90 and Hsp72 using the TranscreenerTM ADP assay kit. J biomol screen, Vol.15 (3), pp. 279-286.  show abstract

Gaspar, N., Sharp, S.Y., Eccles, S.A., Gowan, S., Popov, S., Jones, C., Pearson, A., Vassal, G. & Workman, P. (2010). Mechanistic evaluation of the novel HSP90 inhibitor NVP-AUY922 in adult and pediatric glioblastoma. Mol cancer ther, Vol.9 (5), pp. 1219-1233.  show abstract

Pacey, S., Gore, M., Chao, D., Banerji, U., Larkin, J., Sarker, S., Owen, K., Asad, Y., Raynaud, F., Walton, M., et al. (2010). A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma. Invest new drugs, .  show abstract

Grimshaw, K.M., Hunter, L.J., Yap, T.A., Heaton, S.P., Walton, M.I., Woodhead, S.J., Fazal, L., Reule, M., Davies, T.G., Seavers, L.C., et al. (2010). AT7867 Is a Potent and Oral Inhibitor of AKT and p70 S6 Kinase That Induces Pharmacodynamic Changes and Inhibits Human Tumor Xenograft Growth. Mol cancer ther, Vol.9 (5), pp. 1100-1110.  show abstract

Yap, T.A., Sandhu, S.K., Workman, P. & de Bono, J.S. (2010). Envisioning the future of early anticancer drug development. Nat rev cancer, Vol.10 (7), pp. 514-523.  show abstract

Hayward, D.G., Newbatt, Y., Pickard, L., Byrne, E., Mao, G.J., Burns, S., Sahota, N.K., Workman, P., Collins, I., Aherne, W., et al. (2010). Identification by High-Throughput Screening of Viridin Analogs as Biochemical and Cell-Based Inhibitors of the Cell Cycle-Regulated Nek2 Kinase. J biomol screen, Vol.15 (8), pp. 918-927.  show abstract

Ewan, K., Pajak, B., Stubbs, M., Todd, H., Barbeau, O., Quevedo, C., Botfield, H., Young, R., Ruddle, R., Samuel, L., et al. (2010). A Useful Approach to Identify Novel Small-Molecule Inhibitors of Wnt-Dependent Transcription. Cancer res, Vol.70 (14), pp. 5963-5973.  show abstract

Bavetsias, V., Large, J.M., Sun, C., Bouloc, N., Kosmopoulou, M., Matteucci, M., Wilsher, N.E., Martins, V., Reynisson, J., Atrash, B., et al. (2010). Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J med chem, Vol.53 (14), pp. 5213-5228.  show abstract

Workman, P. & Collins, I. (2010). Probing the probes: fitness factors for small molecule tools. Chem biol, Vol.17 (6), pp. 561-577.  show abstract

Gaspar, N., Sharp, S.Y., Pacey, S., Jones, C., Walton, M., Vassal, G., Eccles, S., Pearson, A. & Workman, P. (2009). Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells. Cancer res, Vol.69 (5), pp. 1966-1975.  show abstract

van Montfort, R.L. & Workman, P. (2009). Structure-based design of molecular cancer therapeutics. Trends biotechnol, Vol.27 (5), pp. 315-328.  show abstract

Raynaud, F.I., Eccles, S.A., Patel, S., Alix, S., Box, G., Chuckowree, I., Folkes, A., Gowan, S., De Haven Brandon, A., Di Stefano, F., et al. (2009). Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol cancer ther, Vol.8 (7), pp. 1725-1738.  show abstract

Brough, P.A., Barril, X., Borgognoni, J., Chene, P., Davies, N.G., Davis, B., Drysdale, M.J., Dymock, B., Eccles, S.A., Garcia-Echeverria, C., et al. (2009). Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J med chem, Vol.52 (15), pp. 4794-4809.  show abstract

Smith, J.R., Clarke, P.A., de Billy, E. & Workman, P. (2009). Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene, Vol.28 (2), pp. 157-169.  show abstract

Gorsuch, S., Bavetsias, V., Rowlands, M.G., Aherne, G.W., Workman, P., Jarman, M. & McDonald, E. (2009). Synthesis of isothiazol-3-one derivatives as inhibitors of histone acetyltransferases (HATs). Bioorg med chem, Vol.17 (2), pp. 467-474.  show abstract

Workman, P. (2009). Drugging the cancer genome. Drug discovery today, (July 2009).

Banerji, U., Affolter, A., Judson, I., Marais, R. & Workman, P. (2008). BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors. Mol cancer ther, Vol.7 (4), pp. 737-739.  show abstract

Chung, Y.L., Troy, H., Kristeleit, R., Aherne, W., Jackson, E., Atadja, P., Griffiths, J.R., Judson, I.R., Workman, P., Leach, M.O., et al. (2008). Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts. Neoplasia, Vol.10 (4), pp. 303-313.  show abstract

Powers, M.V., Clarke, P.A. & Workman, P. (2008). Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer cell, Vol.14 (3), pp. 250-262.  show abstract

Caldwell, J.J., Davies, T.G., Donald, A., McHardy, T., Rowlands, M.G., Aherne, G.W., Hunter, L.K., Taylor, K., Ruddle, R., Raynaud, F.I., et al. (2008). Identification of 4-(4-aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as selective inhibitors of protein kinase B through fragment elaboration. J med chem, Vol.51 (7), pp. 2147-2157.  show abstract

Rayter, S., Elliott, R., Travers, J., Rowlands, M.G., Richardson, T.B., Boxall, K., Jones, K., Linardopoulos, S., Workman, P., Aherne, W., et al. (2008). A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D. Oncogene, Vol.27 (8), pp. 1036-1044.  show abstract

Holmes, J.L., Sharp, S.Y., Hobbs, S. & Workman, P. (2008). Silencing of HSP90 cochaperone AHA1 expression decreases client protein activation and increases cellular sensitivity to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Cancer res, Vol.68 (4), pp. 1188-1197.  show abstract

Eccles, S.A., Massey, A., Raynaud, F.I., Sharp, S.Y., Box, G., Valenti, M., Patterson, L., de Haven Brandon, A., Gowan, S., Boxall, F., et al. (2008). NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer res, Vol.68 (8), pp. 2850-2860.  show abstract

de Bono, J.S., Kristeleit, R., Tolcher, A., Fong, P., Pacey, S., Karavasilis, V., Mita, M., Shaw, H., Workman, P., Kaye, S., et al. (2008). Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors. Clin cancer res, Vol.14 (20), pp. 6663-6673.  show abstract

Brough, P.A., Aherne, W., Barril, X., Borgognoni, J., Boxall, K., Cansfield, J.E., Cheung, K.-., Collins, I., Davies, N.G., Drysdale, M.J., et al. (2008). 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J med chem, Vol.51 (2), pp. 196-218.  show abstract

Vaughan, C.K., Mollapour, M., Smith, J.R., Truman, A., Hu, B., Good, V.M., Panaretou, B., Neckers, L., Clarke, P.A., Workman, P., et al. (2008). Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Mol cell, Vol.31 (6), pp. 886-895.  show abstract

Maloney, A., Clarke, P.A., Naaby-Hansen, S., Stein, R., Koopman, J.O., Akpan, A., Yang, A., Zvelebil, M., Cramer, R., Stimson, L., et al. (2007). Gene and protein expression profiling of human ovarian cancer cells treated with the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Cancer res, Vol.67 (7), pp. 3239-3253.  show abstract

Smith, N.F., Raynaud, F.I. & Workman, P. (2007). The application of cassette dosing for pharmacokinetic screening in small-molecule cancer drug discovery. Mol cancer ther, Vol.6 (2), pp. 428-440.  show abstract

Hardcastle, A., Tomlin, P., Norris, C., Richards, J., Cordwell, M., Boxall, K., Rowlands, M., Jones, K., Collins, I., McDonald, E., et al. (2007). A duplexed phenotypic screen for the simultaneous detection of inhibitors of the molecular chaperone heat shock protein 90 and modulators of cellular acetylation. Mol cancer ther, Vol.6 (3), pp. 1112-1122.  show abstract

Chan, F., Sun, C., Perumal, M., Nguyen, Q.D., Bavetsias, V., McDonald, E., Martins, V., Wilsher, N.E., Raynaud, F.I., Valenti, M., et al. (2007). Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol cancer ther, Vol.6 (12 Pt 1), pp. 3147-3157.  show abstract

Raynaud, F.I., Eccles, S., Clarke, P.A., Hayes, A., Nutley, B., Alix, S., Henley, A., Di-Stefano, F., Ahmad, Z., Guillard, S., et al. (2007). Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer res, Vol.67 (12), pp. 5840-5850.  show abstract

Whittaker, S.R., Te Poele, R.H., Chan, F., Linardopoulos, S., Walton, M.I., Garrett, M.D. & Workman, P. (2007). The cyclin-dependent kinase inhibitor seliciclib (R-roscovitine; CYC202) decreases the expression of mitotic control genes and prevents entry into mitosis. Cell cycle, Vol.6 (24), pp. 3114-3131.  show abstract

Sanderson, S., Valenti, M., Gowan, S., Patterson, L., Ahmad, Z., Workman, P. & Eccles, S.A. (2006). Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol cancer ther, Vol.5 (3), pp. 522-532.  show abstract

Newbatt, Y., Burns, S., Hayward, R., Whittaker, S., Kirk, R., Marshall, C., Springer, C., McDonald, E., Marais, R., Workman, P., et al. (2006). Identification of inhibitors of the kinase activity of oncogenic (V600E)BRAF in an enzyme cascade high-throughput screen. J biomol screen, Vol.11 (2), pp. 145-154.  show abstract

Smith, N.F., Hayes, A., James, K., Nutley, B.P., McDonald, E., Henley, A., Dymock, B., Drysdale, M.J., Raynaud, F.I. & Workman, P., et al. (2006). Preclinical pharmacokinetics and metabolism of a novel diaryl pyrazole resorcinol series of heat shock protein 90 inhibitors. Mol cancer ther, Vol.5 (6), pp. 1628-1637.  show abstract

Burns, S., Travers, J., Collins, I., Rowlands, M.G., Newbatt, Y., Thompson, N., Garrett, M.D., Workman, P. & Aherne, W. (2006). Identification of small-molecule inhibitors of protein kinase B (PKB/AKT) in an AlphaScreen (TM) high-throughput screen. J biomol screen, Vol.11 (7), pp. 822-827.  show abstract

Honma, M., Stubbs, M., Collins, I., Workman, P., Aherne, W. & Watt, F.M. (2006). Identification of novel keratinocyte differentiation modulating compounds by high-throughput screening. J biomol screen, Vol.11 (8), pp. 977-984.  show abstract

Chau, N.-., Rogers, P., Aherne, W., Carroll, V., Collins, I., McDonald, E., Workman, P. & Ashcroft, M. (2005). Identification of novel small molecule inhibitors of hypoxia-inducible factor-1 that differentially block hypoxia-inducible factor-1 activity and hypoxia-inducible factor-1alpha induction in response to hypoxic stress and growth factors. Cancer res, Vol.65 (11), pp. 4918-4928.  show abstract

Banerji, U., Walton, M., Raynaud, F., Grimshaw, R., Kelland, L., Valenti, M., Judson, I. & Workman, P. (2005). Pharmacokinetic-pharmacodynamic relationships for the heat shock protein 90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin in human ovarian cancer xenograft models. Clin cancer res, Vol.11 (19 Pt 1), pp. 7023-7032.  show abstract

Stimson, L., Rowlands, M.G., Newbatt, Y.M., Smith, N.F., Raynaud, F.I., Rogers, P., Bavetsias, V., Gorsuch, S., Jarman, M., Bannister, A., et al. (2005). Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol cancer ther, Vol.4 (10), pp. 1521-1532.  show abstract

Banerji, U., O'Donnell, A., Scurr, M., Pacey, S., Stapleton, S., Asad, Y., Simmons, L., Maloney, A., Raynaud, F., Campbell, M., et al. (2005). Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J clin oncol, Vol.23 (18), pp. 4152-4161.  show abstract

Folkes, A.J., Ahmadi, K., Alderton, W.K., Alix, S., Baker, S.J., Box, G., Chuckowree, I.S., Clarke, P.A., Depledge, P., Eccles, S.A., et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J med chem, Vol.51 (18), pp. 5522-10.  show abstract

Yap, T.A., Smith, A.D., Ferraldeschi, R., Al-Lazikani, B., Workman, P. & de Bono, J.S. Drug discovery in advanced prostate cancer: translating biology into therapy. Nat rev drug discov, Vol.15 (10), pp. 699-718.  show abstract

Rye, C.S., Chessum, N.E., Lamont, S., Pike, K.G., Faulder, P., Demeritt, J., Kemmitt, P., Tucker, J., Zani, L., Cheeseman, M.D., et al. Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9. Medchemcomm, Vol.7 (8), pp. 1580-1586.  show abstract