David P. Fairlie

Inhbitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats (2006)

Gregory, Laura S., Kelly, Wendy L., Reid, Robert R., Fairlie, David P., Forwood, Mark R.

Epidemiological evidence and in vitro data suggest that COX-2 is a key regulator of accelerated remodeling. Accelerated states of osteoblast and osteoclast activity are regulated by prostaglandins in...

Inhbitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats (2006)

Gregory, Laura S., Kelly, Wendy L., Reid, Robert R., Fairlie, David P., Forwood, Mark R.

Epidemiological evidence and in vitro data suggest that COX-2 is a key regulator of accelerated remodeling. Accelerated states of osteoblast and osteoclast activity are regulated by prostaglandins in...

Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A(2) in young spontaneously hypertensive rats (2006)

Levick, Scott, Loch, David, Rolfe, Barbara, Reid, Robert C., Fairlie, David P., Taylor, Stephan M., ...

The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory...

Modular alpha-helical mimetics with antiviral activity against respiratory syncitial virus (2006)

Shepherd, Nicholas E., Hoang, Huy N., Desai, Vishal S., Letouze, Eric, Young, Paul R., Fairlie, David P.

A 13-residue peptide sequence from a respiratory syncitial virus fusion protein was constrained in an alpha-helical conformation by fusing two back-to-back cyclic alpha-turn mimetics. The resulting...

Inhbitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats (2006)

Gregory, Laura S., Kelly, Wendy L., Reid, Robert R., Fairlie, David P., Forwood, Mark R.

Epidemiological evidence and in vitro data suggest that COX-2 is a key regulator of accelerated remodeling. Accelerated states of osteoblast and osteoclast activity are regulated by prostaglandins in...

Site-directed Mutagenesis and Kinetic Studies of the West Nile Virus NS3 Protease Identify Key Enzyme-Substrate Interactions (2005)

Keith J. Chappell, Tessa A. Nall, Martin J. Stoermer, Ning-Xia Fang, David P. Fairlie, ...

A series of papers that have been published since our 2001 paper (above) has built on our understanding of flavivirus protease specificity. We have expanded our studies to incorporate West Nile virus...

Site-directed Mutagenesis and Kinetic Studies of the West Nile Virus NS3 Protease Identify Key Enzyme-Substrate Interactions (2005)

Keith J. Chappell, Tessa A. Nall, Martin J. Stoermer, Ning-Xia Fang, David P. Fairlie, ...

A series of papers that have been published since our 2001 paper (above) has built on our understanding of flavivirus protease specificity. We have expanded our studies to incorporate West Nile virus...

Site-directed mutagenesis and kinetic studies of the West Nile virus NS3 protease identify key enzyme-substrate interactions (2005)

Chappell, Keith J., Nall, Tessa A., Stoermer, Martin J., Fang, Ning-Xia, Tyndall, Joel D. A., Fairlie, David P., ...

The flavivirus West Nile virus (WNV) has spread rapidly throughout the world in recent years causing fever, meningitis, encephalitis, and fatalities. Because the viral protease NS2B/NS3 is essential...

Alpha-Turn Mimetics: Short Peptide -Helices Composed of Cyclic Metallopentapeptide Modules (2004)

Michael J. Kelso, Renée L. Beyer, Huy N. Hoang, Ami S. Lakdawala, James P. Snyder, Warren V. Oliver, ...

Interfering with protein-protein binding is the mode of action of many existing drugs and is a potential mechanistic target in the design of new drugs. Small molecule peptidomimetics are potential...

Countering cooperative effects in protease inhibitors using constrained b-strand-mimicking templates in focused combinatorial libraries (2004)

Reid, Robert C., Pattenden, Lenard K., Tyndall, Joel D. A., Martin, Jennifer L., Walsh, Terry, Fairlie, David P.

A major problem in de novo design of enzyme inhibitors is the unpredictability of the induced fit, with the shape of both ligand and enzyme changing cooperatively and unpredictably in response to...

Formation of mononuclear and chloro-bridged binuclear copper(II) complexes of patellamide D, a naturally occurring cyclic peptide: influence of anion and solvent (2004)

Van Den Brenk, Anna L., Tyndall, Joel D. A., Cusack, Rodney M., Jones, Alun, Fairlie, David P., Gahan, Lawrence R., ...

Patellamide D (patH(4)) is a cyclic octapeptide isolated from the ascidian Lissoclinum patella. The peptide possesses a 24-azacrown-8 macrocyclic structure containing two oxazoline and two thiazole...

Alpha-Turn Mimetics: Short Peptide -Helices Composed of Cyclic Metallopentapeptide Modules (2004)

Michael J. Kelso, Renée L. Beyer, Huy N. Hoang, Ami S. Lakdawala, James P. Snyder, Warren V. Oliver, ...

Interfering with protein-protein binding is the mode of action of many existing drugs and is a potential mechanistic target in the design of new drugs. Small molecule peptidomimetics are potential...

Tumor cell-specific cytotoxicity by targeting cell cycle checkpoints (2003)

Robyn Warrener, Heather Beamish, Andrew Burgess, Nigel J. Waterhouse, Nichole Giles, David P. Fairlie, ...

Warrener and Beamish are joint first authors on this paper. In this paper we demonstrate that the selective targeting of cell cycle checkpoint by chemotherapeutic agents increases the efficacy of the...

Cycloadditions of isobenzofuran to a constrained template bearing neighboring dienophiles (2003)

Stoermer, Martin J., Weerasuria, K. D. V., Fairlie, David P.

A high yielding synthesis of the pentacyclic diene ± dione 1 has enabled investigation of its reactivity as a double dienophile in Diels ±Alder [4 2] cycloadditions with isobenzofuran, leading to...

Tumor cell-specific cytotoxicity by targeting cell cycle checkpoints (2003)

Robyn Warrener, Heather Beamish, Andrew Burgess, Nigel J. Waterhouse, Nichole Giles, David P. Fairlie, ...

Warrener and Beamish are joint first authors on this paper. In this paper we demonstrate that the selective targeting of cell cycle checkpoint by chemotherapeutic agents increases the efficacy of the...

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug (2003)

Reid, Robert C., Abbenante, Giovanni, Taylor, Stephen M., Fairlie, David P.

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of...

Activity of Recombinant Dengue 2 Virus NS3 Protease in the Presence of a Truncated NS2B Co-factor, Small Peptide Substrates, and Inhibitors (2001)

Donmienne Leung, Kate Schroder, Helen White, Ning-Xia Fang, Martin J. Stoermer, Giovanni Abbenante, ...

Our paper describes the expression and purification of the first active recombinant flavivirus protease suitable for in vitro assays. We used this assay to probe substrate specificity and develop the...

Histone Deacetylase Inhibitors Trigger a G2 Checkpoint in Normal Cells That Is Defective in Tumor Cells

Qiu, Ling, Burgess, Andrew, Fairlie, David P., Leonard, Helen, Parsons, Peter G., Gabrielli, Brian G.

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic...

Potencies of Human Immunodeficiency Virus Protease Inhibitors In Vitro against Plasmodium falciparum and In Vivo against Murine Malaria

Andrews, Katherine T., Fairlie, David P., Madala, Praveen K., Ray, John, Wyatt, David M., Hilton, Petrina M., ...

Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for...

Histone Deacetylase Inhibitors Trigger a G2 Checkpoint in Normal Cells That Is Defective in Tumor Cells

Qiu, Ling, Burgess, Andrew, Fairlie, David P., Leonard, Helen, Parsons, Peter G., Gabrielli, Brian G.

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic...

Potencies of Human Immunodeficiency Virus Protease Inhibitors In Vitro against Plasmodium falciparum and In Vivo against Murine Malaria

Andrews, Katherine T., Fairlie, David P., Madala, Praveen K., Ray, John, Wyatt, David M., Hilton, Petrina M., ...

Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for...

Effects of a new C5a receptor antagonist on C5a- and endotoxin- induced neutropenia in the rat

Short, Anna, Wong, Allan K, Finch, Angela M, Haaima, Gerald, Shiels, Ian A, Fairlie, David P, ...

A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin...

Pharmacological characterization of antagonists of the C5a receptor

Paczkowski, Natalii J, Finch, Angela M, Whitmore, Jacqueline B, Short, Anna J, Wong, Allan K, Monk, Peter N, ...

Potent and highly selective small molecule antagonists have recently been developed by us for C5a receptors (C5aR) on human polymorphonuclear leukocytes (PMN). In this study we compared a new cyclic...

Inhibition of immune-complex mediated dermal inflammation in rats following either oral or topical administration of a small molecule C5a receptor antagonist

Strachan, Anna J, Shiels, Ian A, Reid, Robert C, Fairlie, David P, Taylor, Stephen M

Initiation of a peritoneal Arthus reaction by deposition of immune-complexes results in vascular leakage, polymorphonuclear leukocyte (PMN) infiltration, and tumour necrosis factor α (TNFα) and...

Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist

Arumugam, Thiruma V, Arnold, Naomi, Proctor, Lavinia M, Newman, Michelle, Reid, Robert C, Hansford, Karl A, ...

A new group IIa sPLA2 inhibitor was compared with selective inhibitors of COX-1, COX-2 and an LTC4 antagonist for effects on local and remote tissue injuries following ischaemia and reperfusion (I/R)...

Comparative anti-inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury

Proctor, Lavinia M, Arumugam, Thiruma V, Shiels, Ian, Reid, Robert C, Fairlie, David P, Taylor, Stephen M

Complement activation is implicated in the pathogenesis of intestinal ischaemia–reperfusion injury (I/R), although the relative importance of individual complement components is unclear. A C3a...

Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death

Arumugam, Thiruma V., Tang, Sung-Chun, Lathia, Justin D., Cheng, Aiwu, Mughal, Mohamed R., Chigurupati, Srinivasulu, ...

Stroke is among the three leading causes of death worldwide and the most frequent cause of permanent disability. Brain ischemia induces an inflammatory response involving activated complement...

Activity of Recombinant Dengue 2 Virus NS3 Protease in the Presence of a Truncated NS2B Co-factor, Small Peptide Substrates, and Inhibitors

Donmienne Leung, Kate Schroder, Helen White, Ning-Xia Fang, Martin J. Stoermer, Giovanni Abbenante, ...

Our paper describes the expression and purification of the first active recombinant flavivirus protease suitable for in vitro assays. We used this assay to probe substrate specificity and develop the...

Inhibitory effects of bisbenzylisoquinolines on synthesis of the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha

Seow, W. Kim, Nakamura, Kazuhiro, Sugimura, Yukio, Sugimoto, Yukihiro, Yamada, Yasuyuki, Fairlie, David P., ...

Synthesis of IL-1β and TNFα by human monocytesmacrophages was significantly inhibited by eleven bisbenzylisoquinolines and one half-molecule (benzylisoquinoline), with IC50 values in the μM range....