Signal Transduction and Molecular Pharmacology Team Publications

Team Leader: Professor Paul Workman

Location: Haddow Laboratories

Section: Cancer Research UK Cancer Therapeutics Unit

Publications

N Gaspar; SY Sharp; S Pacey; C Jones; M Walton; G Vassal; A Pearson; P Workman. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (tanespimicin; 17-AAG) in glioblastoma cell lines. Cancer Res 69: 1966-75, 2009

C Prodromou; JM Nuttall; SH Millson; MS Roe; S Tiow-Suan; D Tan; P Workman; LH Pearl; PW Piper. Crystal structures reveal how an amino acid substitution in Hsp90 generates radicicol resistance. ACS Chem Biol 2009 in press

S Guillard ; PA Clarke; R Te Poele; Z Mohri; L Bjerke; M Valenti; F Raynaud; SA Eccles; P Workman. Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma. Cell Cycle 8: 443-53, 2009

MV Powers; PA Clarke; P Workman. Dual targeting HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell 14: 250-62, 2008

JR Smith; PA Clarke; E de Billy; P Workman. Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene 28: 157-69, 2009

AJ Folkes; K Ahmadi; WK Alderton; S Alix; SJ Baker; G Box; IS Chuckowree; PA Clarke; P Depledge; SA Eccles; LS Friedman; A Hayes; TC Hancox; A Kugendradas; L Lensun; P Moore; AG Olivero; J Pang; S Patel; GH Pergl-Wilson; FI Raynaud; A Robson; N Saghir; L Salphati; S Sohal; MH Ultsch; M Valenti; HJ Wallweber; NC Wan; C Wiesmann; P Workman; A Zhyvoloup; MJ Zvelebil; SJ Shuttleworth. 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 51: 5522-32, 2008

SA Eccles; A Massey; FI Raynaud; SY Sharp; G Box; M Valenti; L Patterson; S Gowan; F Boxall; W Aherne; M Rowlands; A Hayes; V Martins; F Urban; K Boxall; C Prodromou; L Pearl; K James; TP Matthews; KM Cheung; A Kalusa; K Jones; E McDonald; X Barril; PA Brough; JE Cansfield; B Dymock; MJ Drysdale; H Finch; R Howes; RE Hubbard; A Surgenor; P Webb; M Wood; L Wright; P Workman. NVP-AUY922: A novel HSP90 inhibitor active against xenograft tumor growth; angiogenesis and metastasis. Cancer Res 68: 2850-60, 2008

JL Holmes; SY Sharp; S Hobbs; P Workman. Silencing of HSP90 cochaperone AHA1 expression decreases client protein activation and increases cellular sensitivity to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Cancer Res 68: 1188-97, 2008

Cheung KM; Matthews TP; James K; Rowlands MG; Boxall KJ; Sharp SY; Maloney A; Roe SM; Prodromou C; Pearl LH; Aherne GW; McDonald E; Workman P. The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrzole class of Hsp90 inhibitors. Bioorg Med Chem Lett 15: 3338-3343, 2005

Hostein I; Robertson D; Di Stefano D; Workman P; Clarke PA. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res 61: 4003-4009, 2001

Banerji U; Walton M; Raynaud F; Grimshaw R; Kelland L; Valenti M; Judson I; Workman P; 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 11: 7023-7032, 2005

Dymock BW; Barril X; Brough PA; Cansfield JE; Massey A; McDonald E; Hubbard RE; Surgenor A; Roughley SD; Webb P; Workman P; Wright L; Drysdale MJ. Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design. J Med Chem 48: 4212-4215, 2005

Whittaker SR; Walton MI; Garrett MD; Workman P. The cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res 64: 262-272, 2004

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