Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice

…, SL Graham, K Hamilton, LK Handt, GD Hartman… - Nature medicine, 1995 - nature.com
For Ras oncoproteins to transform mammalian cells, they must be post-translationally modified
with a farnesyl group in a reaction catalysed by the enzyme farnesyl-protein transferase (…

Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors

…, D Defeo-Jones, RE Jones, GD Hartman… - Bioorganic & medicinal …, 2005 - Elsevier
This letter describes the development of two series of potent and selective allosteric Akt
kinase inhibitors that display an unprecedented level of selectivity for either Akt1, Akt2 or both …

Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors

GD Hartman, MS Egbertson, W Halczenko… - Journal of medicinal …, 1992 - ACS Publications
When a blood vessel is injured, either by the acute damage of wounding or clinical interventions,
or more chronically by the pathophysiological processes of ath-erosclerosis, platelets …

Discovery of the Dual Orexin Receptor Antagonist [(7R)-4-(5-Chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl] …

…, S Roller, TD Cabalu, D Cui, GD Hartman… - Journal of medicinal …, 2010 - ACS Publications
Despite increased understanding of the biological basis for sleep control in the brain, few
novel mechanisms for the treatment of insomnia have been identified in recent years. One …

Evaluation of farnesyl: protein transferase and geranylgeranyl: protein transferase inhibitor combinations in preclinical models

…, E Rands, TM Williams, SL Graham, GD Hartman… - Cancer research, 2001 - AACR
Farnesyl:protein transferase (FPTase) inhibitors (FTIs) were originally developed as potential
anticancer agents targeting the ras oncogene and are currently in clinical trials. Whereas …

Inhibition of a mitotic motor protein: where, how, and conformational consequences

…, CA Buser, M Schaber, GD Hartman… - Journal of molecular …, 2004 - Elsevier
We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9Å resolution
structure of the motor domain of KSP, bound with the small molecule monastrol and Mg 2+ …

Discovery of 2, 3, 5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors

…, D Defeo-Jones, RE Jones, GD Hartman… - Bioorganic & medicinal …, 2005 - Elsevier
This letter describes the discovery of a novel series of dual Akt1/Akt2 kinase inhibitors,
based on a 2, 3, 5-trisubstituted pyridine scaffold. Compounds from this series, which …

Discovery of Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 5 from a Series of N-(1,3-Diphenyl-1H- pyrazol-5-yl)benzamides That …

…, S Smith, ME Duggan, GD Hartman… - Journal of medicinal …, 2004 - ACS Publications
This report describes the discovery of the first centrally active allosteric modulators of the
metabotropic glutamate receptor subtype 5 (mGluR5). Appropriately substituted N-(1,3-diphenyl…

Kinesin Spindle Protein (KSP) Inhibitors. 9. Discovery of (2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5 …

…, Y Yan, LC Kuo, NE Kohl, GD Hartman - Journal of medicinal …, 2008 - ACS Publications
Inhibition of kinesin spindle protein (KSP) is a novel mechanism for treatment of cancer with
the potential to overcome limitations associated with currently employed cytotoxic agents. …

Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp

…, RJ Gould, W Halczenko, GD Hartman… - Journal of medicinal …, 1994 - ACS Publications
Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9
nM and demonstrated a selectivity of> 24 000-fold between platelet and human umbilical …