Journal: PLoS ONE

Article Title: Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

doi: 10.1371/journal.pone.0027682

Figure Lengend Snippet: In vitro growth rates of cells harboring resistance mutations [8] .

Article Snippet: The small molecule inhibitor imatinib mesylate (Gleevec, Novartis) induces a complete cytogenetic response in over of patients with chronic phase CML .

Techniques: In Vitro

Journal: PLoS ONE

Article Title: Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

doi: 10.1371/journal.pone.0027682

Figure Lengend Snippet: In vivo growth rates of cells harboring resistance mutations.

Article Snippet: The small molecule inhibitor imatinib mesylate (Gleevec, Novartis) induces a complete cytogenetic response in over of patients with chronic phase CML .

Techniques: In Vivo

Journal: PLoS ONE

Article Title: Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

doi: 10.1371/journal.pone.0027682

Figure Lengend Snippet: (a) The panel displays the probability that there exists at least one cell with any specified mutation in the CML stem cell population at detection time. Parameters are and . (b) The probability that the leukemic stem cell population is free of mutants conferring resistance to imatinib, dasatinib, imatinib plus dasatinib, and all three drugs at detection time. Parameters are (red), (blue), and .

Article Snippet: The small molecule inhibitor imatinib mesylate (Gleevec, Novartis) induces a complete cytogenetic response in over of patients with chronic phase CML .

Techniques: Mutagenesis

Journal: Genome Medicine

Article Title: The expressed mutational landscape of microsatellite stable colorectal cancers

doi: 10.1186/s13073-021-00955-2

Figure Lengend Snippet: Correlation between TP53 and RAS / BRAF V600E mutation expression levels and sensitivity to targeted anticancer agents in pre-clinical models. a Sensitivity to the EGFR inhibitor erlotinib, the MEK inhibitor trametinib, and the MDM2 inhibitor idasanutlin in a panel of 29 unique CRC cell lines plotted according to RAS / BRAF V600E or TP53 mutation status, as indicated (mut, mutated; wt, wild-type; color codes are shown in c ). Higher DSS indicates stronger sensitivity. p -value is from Welch’s t -test of wild-type versus mutated samples. b , c Upper panels show the mutation status for RAS / BRAF V600E and TP53 in each of the 7 selected cell lines and 8 patient-derived organoids (PDOs). Scatter plots show the DSS of matched drugs versus mutant allele expression levels (color-coded as indicated). Spearman’s correlations in blue are for KRAS -mutated PDOs only (excluding the single NRAS -mutated sample). d Scatter plot of RNA-level versus DNA-level MAFs of RAS and TP53 in matched primary and metastatic tumor samples from each of four patients (three with RAS mutations and two with TP53 mutations). Patient 2 showed higher relative expression of the RAS mutant allele in the metastasis

Article Snippet: The MDM2-TP53 inhibitor idasanutlin (MedChemExpress, Monmouth Junction, NJ, USA), three EGFR inhibitors (afatinib: Selleck Chemicals; erlotinib: MedChemExpress; and lapatinib: LC Laboratories, Woburn, MA, USA) and two MEK inhibitors (binimetinib and trametinib, ChemieTek, Indianapolis, IN, USA) were included in the screens at five and nine different concentrations over a 10,000-fold concentration range each (typically 1–10,000 nmol/L) in the cell lines and PDOs, respectively.

Techniques: Mutagenesis, Expressing, Derivative Assay

Journal: Journal of medicinal chemistry

Article Title: Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer

doi: 10.1021/acs.jmedchem.3c00917

Figure Lengend Snippet: Examples of reported inhibitors of m7GpppX cap binding to eIF4E and proposed acyclic nucleoside phosphonate prodrugs inspired by the anti-viral drugs, adefovir and tenofovir dipivoxil.

Article Snippet: These compounds, in addition to recently reported small molecule eIF4E inhibitors reported by eFFECTOR Therapeutics, 40 will provide important tools for validating eIF4E as an anti-cancer therapeutic target, as well as provide new insights into the role of cap-dependent translation in cancer and other relevant human diseases.

Techniques: Binding Assay

Journal: Journal of medicinal chemistry

Article Title: Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer

doi: 10.1021/acs.jmedchem.3c00917

Figure Lengend Snippet: eIF4E bound to 7n. The eIF4E protein backbone is shown as a gray ribbon with residues that interact with 7n shown as sticks. 7n is shown as sticks with cyan carbons. Nitrogen atoms are colored blue, oxygens in red and phosphorus in orange. Dashed lines represent hydrogen bonds (PDB: 8SX4).

Article Snippet: These compounds, in addition to recently reported small molecule eIF4E inhibitors reported by eFFECTOR Therapeutics, 40 will provide important tools for validating eIF4E as an anti-cancer therapeutic target, as well as provide new insights into the role of cap-dependent translation in cancer and other relevant human diseases.

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer

doi: 10.1021/acs.jmedchem.3c00917

Figure Lengend Snippet: Activation of eIF4E and cap-dependent translation.

Article Snippet: These compounds, in addition to recently reported small molecule eIF4E inhibitors reported by eFFECTOR Therapeutics, 40 will provide important tools for validating eIF4E as an anti-cancer therapeutic target, as well as provide new insights into the role of cap-dependent translation in cancer and other relevant human diseases.

Techniques: Activation Assay

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Inhibition of αvβ6 integrin or TGFβR1 induce proliferation in primary human bladder epithelial cells in culture. All proliferation measurements were assessed following 3 days of exposure to treatments. Selective αvβ6 integrin inhibitor, MORF-627 (A). Structurally distinct tool αvβ6 integrin inhibitor (B). TGFβR1 multikinase inhibitor (C). Proliferative changes induced by MORF-627 were reversed by concomitant incubation of test agent with exogenous TGF-β (D). Graphs represent 3 independent experiments, with each concentration run in triplicate per study. All data are plotted as raw luminescence mean ± SEM; * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 2-tailed unpaired t -test with Welsh’s correction.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Inhibition, Incubation, Concentration Assay

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Inhibition of αvβ6 integrin or TGFβR1 induce proliferation in primary human alveolar epithelial cells in culture. All proliferation measurements were assessed following 3 days of exposure to treatments. Selective αvβ6 integrin inhibitor, MORF-627 (A). Structurally distinct tool αvβ6 integrin inhibitor (B). TGFβR1 multikinase inhibitor (C). Proliferative changes induced by MORF-627 were reversed by concomitant incubation of test agent with exogenous TGF-β (D). Graphs represent 3 independent experiments, with each concentration run in triplicate per study. All data are plotted as raw luminescence mean ± SEM; * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 2-tailed unpaired t -test with Welsh’s correction.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Inhibition, Incubation, Concentration Assay

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Tool αvβ6 inhibitor and TGFβR1 selective inhibitor increased biliary epithelial cell proliferation in DDC-induced biliary fibrosis model. A, Representative images of IHC staining for CK19 expressing epithelial cells in healthy mice ( n = 5) and mice fed with DDC diet with or without treatment ( n = 9–15/group). Scale bar = 200 µm. B, IHC quantification of CK19 expressing biliary epithelial cells. (**** p < .0001 indicate statistical significance compared with DDC vehicle group, using 1-way ANOVA with Dunnett’s post hoc test.) C, IHC quantification of Ki67 positive proliferating cells (* p < .05, ** p < .01 indicate statistical significance compared with DDC vehicle group using 2-tailed Student’s T test). All data are shown as means ± SEM.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Immunohistochemistry, Expressing

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Anti-αvβ6 antibody (3G9) increased biliary epithelial cell proliferation in DDC-induced biliary fibrosis model. A, IHC quantification of CK19 expressing epithelial cells in healthy mice and mice fed with DDC diet with or without treatment ( n = 10/group). B, IHC quantification of Ki67 positive proliferating cells. C, KEGG pathway analysis of bulk RNA sequencing data from liver tissues. All data are shown as means ± SEM. * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with DDC vehicle group, using 1-way ANOVA with Dunnett’s post hoc test.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Expressing, RNA Sequencing

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Anti-αvβ6 antibody (3G9) promoted cell proliferation in bleomycin-induced lung fibrosis model. A, KEGG pathway analysis of bulk RNA sequencing data from lung tissues. mRNA levels of cell cycle genes, (B) Mki67 and (C) Pcna, in lung tissues. All data are shown as means ± SEM. * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 1-way ANOVA with Dunnett’s post hoc test.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: RNA Sequencing

Journal: Journal of Clinical Medicine

Article Title: Anticoagulation Management: Current Landscape and Future Trends

doi: 10.3390/jcm14051647

Figure Lengend Snippet: FDA-Approved Anticoagulants.

Article Snippet: ONO-7684 , Small-molecule factor XIa inhibitor [ ] , Intravenous , ONO Pharmaceuticals , Undisclosed.

Techniques: Coagulation, Molecular Weight, Inhibition, Injection, Binding Assay

Journal: Journal of Clinical Medicine

Article Title: Anticoagulation Management: Current Landscape and Future Trends

doi: 10.3390/jcm14051647

Figure Lengend Snippet: FXI-Anticoagulants in Development.

Article Snippet: ONO-7684 , Small-molecule factor XIa inhibitor [ ] , Intravenous , ONO Pharmaceuticals , Undisclosed.

Techniques: Clinical Proteomics, Activation Assay, Coagulation