Martin G. Rowlands

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We describe the biological properties of NVP-AUY922, a novel resorcinylic isoxazole amide heat shock protein 90 (HSP90) inhibitor. NVP-AUY922 potently inhibits HSP90 (K(d) = 1.7 nmol/L) and proliferation of human tumor cells with GI(50) values of approximately 2 to 40 nmol/L, inducing G(1)-G(2) arrest and apoptosis. Activity is independent of(More)
The molecular chaperone heat-shock protein 90 (HSP90) plays a key role in the cell by stabilizing a number of client proteins, many of which are oncogenic. The intrinsic ATPase activity of HSP90 is essential to this activity. HSP90 is a new cancer drug target as inhibition results in simultaneous disruption of several key signaling pathways, leading to a(More)
Steroidal compounds having a 17-(3-pyridyl) substituent together with a 16,17-double bond have been synthesized, using a palladium-catalyzed cross-coupling reaction of a 17-enol triflate with diethyl(3-pyridyl)borane, which are potent inhibitors of human testicular 17 alpha-hydroxylase-C17,20-lyase. The requirement for these structural features is(More)
The role of histone acetyltransferases (HATs) in the regulation of crucial cellular functions, e.g., gene transcription, differentiation, and proliferation, has recently been documented and there is increasing evidence that aberrant expression of these enzymes may have a role to play in the development of the malignant phenotype. The availability of potent(More)
Intratumoral aromatase activity (AA) was measured in 145 samples of human primary breast carcinoma using the tritiated water release assay which quantifies the tritium lost to water during the aromatization of 1 beta-[3H]androstenedione to estrone. Significant AA was detected in 91/145 (63%) tumors. The possibility of a relationship between AA and a variety(More)
Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer(More)
The PPM1D gene is aberrantly amplified in a range of common cancers and encodes a protein phosphatase that is a potential therapeutic target. However, the issue of whether inhibition of PPM1D in human tumour cells that overexpress this protein compromises their viability has not yet been fully addressed. We show here, using an RNA interference (RNAi)(More)
The role of intratumoural aromatase in human breast cancer growth remains controversial. At the same time as the use of aromatase inhibitors in the clinical setting continues to increase, so does the need for a tool to predict the likely response to this treatment. Intratumoural aromatase is a candidate predictive marker. The presently accepted 'gold(More)
Ire1 (Ern1) is an unusual transmembrane protein kinase essential for the endoplasmic reticulum (ER) unfolded protein response (UPR). Activation of Ire1 by association of its N-terminal ER luminal domains promotes autophosphorylation by its cytoplasmic kinase domain, leading to activation of the C-terminal ribonuclease domain, which splices Xbp1 mRNA(More)
R115777 (Zarnestra) is a farnesyl protein transferase inhibitor currently undergoing worldwide clinical trials. As acquired drug resistance may limit the efficacy of the drug, a model of acquired resistance has been established in vitro by continuous drug exposure of the human colon cancer cell line KM12. A stably resistant cell line possessing 13-fold(More)