Alexandra E. Gould
YOU?
Author Swipe
View article: Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform
Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform Open
PPM1D is a serine/threonine phosphatase recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses p53. Though PPM1D inhibition impairs tumor growth in cancer models and is the subject of multiple drug discove…
View article: A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo
A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i>
A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i> Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform
Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform Open
Protein phosphatase, Mg 2+ /Mn 2+ dependent 1D (PPM1D), is a serine/threonine phosphatase that is recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses the activation of p53. Consistent with its oncogenic…
View article: Supplementary Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Supplementary Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Open
Supplementary Tables (S1-6) and Figures (S1-6)
View article: Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Open
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting
View article: Supplementary Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Supplementary Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Open
Supplementary Tables (S1-6) and Figures (S1-6)
View article: Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Open
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting
View article: Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome
Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome Open
View article: Target-driven machine learning-enabled virtual screening (TAME-VS) platform for early-stage hit identification
Target-driven machine learning-enabled virtual screening (TAME-VS) platform for early-stage hit identification Open
High-throughput screening (HTS) methods enable the empirical evaluation of a large scale of compounds and can be augmented by virtual screening (VS) techniques to save time and money by using potential active compounds for experimental tes…
View article: Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non–small cell lung cancer
Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non–small cell lung cancer Open
In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resi…
View article: Susceptibilities of Ugandan Plasmodium falciparum Isolates to Proteasome Inhibitors
Susceptibilities of Ugandan Plasmodium falciparum Isolates to Proteasome Inhibitors Open
The proteasome is a promising target for antimalarial chemotherapy. We assessed ex vivo susceptibilities of fresh Plasmodium falciparum isolates from eastern Uganda to seven proteasome inhibitors: two asparagine ethylenediamines, two macro…
View article: Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy
Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy Open
Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5′-monophosphate–mimicking nucleoside sulfamates. The target enzyme catalyz…
View article: Design of proteasome inhibitors with oral efficacy in vivo against <i>Plasmodium falciparum</i> and selectivity over the human proteasome
Design of proteasome inhibitors with oral efficacy in vivo against <i>Plasmodium falciparum</i> and selectivity over the human proteasome Open
Significance Here, we describe inhibitors of the Plasmodium proteasome, an enzymatic complex that malaria parasites rely on to degrade proteins. Starting from inhibitors developed to treat cancer, derivatives were designed and synthesized …
View article: Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route
Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route Open
Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammati…
View article: Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Open
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSC…
View article: Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors
Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors Open
Autophagy is postulated to be required by cancer cells to survive periods of metabolic and/or hypoxic stress. ATG7 is the E1 enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This artic…
View article: Target Validation and Identification of Novel Boronate Inhibitors of the <i>Plasmodium falciparum</i> Proteasome
Target Validation and Identification of Novel Boronate Inhibitors of the <i>Plasmodium falciparum</i> Proteasome Open
The Plasmodium proteasome represents a potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities…
View article: Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG
Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG Open