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Papers by Philip Harris
Http Dx Doi Org 10 1080 00304949409458025, Feb 18, 2009
Http Dx Doi Org 10 1080 00304940309355359, Feb 9, 2009
Synthesis Stuttgart, 1990
Cell Death & Disease
ABSTRACT
Bioorganic & medicinal chemistry letters, 2015
The RAS-RAF-MEK-ERK, or ERK signaling pathway propagates signals through an intracellular signal ... more The RAS-RAF-MEK-ERK, or ERK signaling pathway propagates signals through an intracellular signal transduction cascade. Since approximately one third of human cancers are impacted by mutations in the ERK signaling pathway, intensive efforts to develop drugs targeting members of this cascade are ongoing. While efforts to develop drugs aimed at inhibiting RAS are still at an early stage, substantial progress in discovering clinical drugs targeting RAF, MEK, and ERK have been made. This review will highlight the recent progress in this area.
Bioorganic & medicinal chemistry letters, Jan 19, 2015
Nod-like receptors (NLRs) are cytoplasmic pattern recognition receptors that are promising target... more Nod-like receptors (NLRs) are cytoplasmic pattern recognition receptors that are promising targets for the development of anti-inflammatory therapeutics. Drug discovery efforts targeting NLRs have been hampered by their inherent tendency to form aggregates making protein generation and the development of screening assays very challenging. Herein we report the results of an HTS screen of NLR family member NLRP1 (NLR family, pyrin domain-containing 1) which was achieved through the large scale generation of recombinant GST-His-Thrombin-NLRP1 protein. The screen led to the identification of a diverse set of ATP competitive inhibitors with micromolar potencies. Activity of these hits was confirmed in a FP binding assay, and two homology models were employed to predict the possible binding mode of the leading series and facilitate further lead-optimization. These results highlight a promising strategy for the identification of inhibitors of NLR family members which are rapidly emerging a...
Tetrahedron, 2015
Dedicated to the memory of Alan R. Katritzky, an invaluable mentor, friend, and scientific collab... more Dedicated to the memory of Alan R. Katritzky, an invaluable mentor, friend, and scientific collaborator over the last 25 years a b s t r a c t
ChemInform, 2001
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Http Dx Doi Org 10 1080 00304949409458025, Feb 18, 2009
Http Dx Doi Org 10 1080 00304940309355359, Feb 9, 2009
Synthesis Stuttgart, 1990
Cell Death & Disease
ABSTRACT
Bioorganic & medicinal chemistry letters, 2015
The RAS-RAF-MEK-ERK, or ERK signaling pathway propagates signals through an intracellular signal ... more The RAS-RAF-MEK-ERK, or ERK signaling pathway propagates signals through an intracellular signal transduction cascade. Since approximately one third of human cancers are impacted by mutations in the ERK signaling pathway, intensive efforts to develop drugs targeting members of this cascade are ongoing. While efforts to develop drugs aimed at inhibiting RAS are still at an early stage, substantial progress in discovering clinical drugs targeting RAF, MEK, and ERK have been made. This review will highlight the recent progress in this area.
Bioorganic & medicinal chemistry letters, Jan 19, 2015
Nod-like receptors (NLRs) are cytoplasmic pattern recognition receptors that are promising target... more Nod-like receptors (NLRs) are cytoplasmic pattern recognition receptors that are promising targets for the development of anti-inflammatory therapeutics. Drug discovery efforts targeting NLRs have been hampered by their inherent tendency to form aggregates making protein generation and the development of screening assays very challenging. Herein we report the results of an HTS screen of NLR family member NLRP1 (NLR family, pyrin domain-containing 1) which was achieved through the large scale generation of recombinant GST-His-Thrombin-NLRP1 protein. The screen led to the identification of a diverse set of ATP competitive inhibitors with micromolar potencies. Activity of these hits was confirmed in a FP binding assay, and two homology models were employed to predict the possible binding mode of the leading series and facilitate further lead-optimization. These results highlight a promising strategy for the identification of inhibitors of NLR family members which are rapidly emerging a...
Tetrahedron, 2015
Dedicated to the memory of Alan R. Katritzky, an invaluable mentor, friend, and scientific collab... more Dedicated to the memory of Alan R. Katritzky, an invaluable mentor, friend, and scientific collaborator over the last 25 years a b s t r a c t
ChemInform, 2001
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.