Validation of select PDN drug candidates in an in vivo endotoxemia model Validation of select PDN drug candidates in an in vivo endotoxemia model Therapeutic.

Slides:



Advertisements
Similar presentations
Culture type shapes drug‐induced growth arrest in ovarian cancer patient cells Culture type shapes drug‐induced growth arrest in ovarian cancer patient.
Advertisements

Abundance of proteins matching selected subcellular locations and functions in CaCo‐2 cells. Abundance of proteins matching selected subcellular locations.
Global comparison of MinSpan pathways with databases of human‐defined pathways The pairwise connection specificity index (CSI) was calculated for all pathway.
Schematic diagram of the three circuits analysed in this work.
Attema et al., Supplementary Figure 1
Melting behavior of proteins identified in the Escherichia coli meltome and their properties Melting behavior of proteins identified in the Escherichia.
Overview of the experimental setting.
Thermal proteome profiling in Escherichia coli
Melting behavior of protein complexes
In vivo selectivity of compound 6b.
Analysis of in silico flux changes along the exponential growth phase: (A) In silico flux changes from 24 to 36 h, from 36 to 48 h, and from 48 to 60 h.
Heatmaps of the gene mutation distributions in oncogene‐signaling blocks for six representative cancer types. Heatmaps of the gene mutation distributions.
Validation of the CCE associations by mass spectrometry.
Treatment with p38γ/p38δ inhibitor shows antifungal effects in vivo
Skin proliferation kinetics and in vivo fibroblast lineage tracing during dermal maturation (related to Fig 4)‏ Skin proliferation kinetics and in vivo.
Prediction of IGHV status based on Factor 1 in the CLL data and validation on outlier cases on independent assays Prediction of IGHV status based on Factor.
Dose response of pAGA1 and pFIG1 induction
Correlating protein to mRNA and proteins per mRNA ratios
Characterization of promoters relative to pAGA1
Drug network derived from the core EGFR interactome and combination strategy to overcome the resistant cells. Drug network derived from the core EGFR interactome.
EGFL7 affected tumor growth and reduced overall survival
SKAP55‐deficient mice enhance DC‐based vaccine for prevention of tumors in vivo AWT and SKAP55 KO C57BL/6 mice were s.c. immunized on day −14 and day −7.
Networks of ERK substrates.
The limiting, degrading entity hypothesis
Feature‐based COG enrichment analysis
BETi potentiate the efficacy of MEKi in NRAS‐mutant melanoma
USP9X and XIAP promote lymphoma growth and resistance to spindle poisons in vivo USP9X and XIAP promote lymphoma growth and resistance to spindle poisons.
Lysozyme expression in isolated Paneth cells and linage tracing of Notch1+ cells Lysozyme expression in isolated Paneth cells and linage tracing of Notch1+
Characterization of Factor 5 (oxidative stress response factor) in the CLL data Characterization of Factor 5 (oxidative stress response factor) in the.
Patient organoids respond more diverse to drugs and with lower therapeutic potential than 2D cultured patient cells Patient organoids respond more diverse.
Chemical inhibitors of microtubule function attenuate signal but do not affect pathway variability Chemical inhibitors of microtubule function attenuate.
Computational wound healing gradients and in vivo imaging of the wound bed at PW2 (related to Fig 6)‏ Computational wound healing gradients and in vivo.
DeathPro dyes Hoechst and PI do not affect organoid growth and drug responses DeathPro dyes Hoechst and PI do not affect organoid growth and drug responses.
Association of cryptococci with the brain endothelium requires Mpr1 in the tail-vein murine model. Association of cryptococci with the brain endothelium.
Francis Crick's central dogma of biology revolves around the transcription of mRNA from DNA, the translation of proteins from mRNA, and the degradation.
QRT–PCR analysis of tissue‐specific candidate gene expression in response to reduced IIS qRT–PCR analysis of tissue‐specific candidate gene expression.
Allele‐specific expression at single‐cell resolution
Two‐way unsupervised uncentered unnormalized hierarchical clustering using a Pearson's correlation of the phenotypic profiles of 4281 nonessential genes.
Transcriptomic and epigenetic changes associated with Factor 1 in the scMT data Transcriptomic and epigenetic changes associated with Factor 1 in the scMT.
48 clinically relevant GPCR receptors mapped using MYTH
Live‐cell imaging uncovers a slowly cycling drug‐resistant state involved in adaptation to RAF inhibition Live‐cell imaging uncovers a slowly cycling drug‐resistant.
Development of a 3D tissue model and in vivo live imaging during dermal maturation Development of a 3D tissue model and in vivo live imaging during dermal.
Impact of growth phase on the Escherichia coli meltome and proteome
Simulation showing that the cell length variability of the entire population can mask abnormal cell length variability at a specific cell cycle period.
In vivo efficacy of Olaparib in PTEN deficient xenografts.
An integrated NHR network.
Proliferative advantage depends on environmental dynamics
Reproducibility of DeathPro drug screens
When grown with biofuel, strains with beneficial pumps dominate the culture. When grown with biofuel, strains with beneficial pumps dominate the culture.
Melting behavior of protein complexes
In vivo imaging of the wound bed at later time points (related to Fig 7)‏ In vivo imaging of the wound bed at later time points (related to Fig 7) A–CRepresentative.
Experimental validation of predicted endocytosis functions in human.
Drug sensitivity described by LD50 is similar in cells cultured in 2D or as organoids Drug sensitivity described by LD50 is similar in cells cultured in.
Therapeutic role of TR in HFD‐established diabetic mice
Global and focused views of human interaction map.
Schematics for nutrient pulse systems
Rare and abundant codons.
BT_0370 galactokinase and BT_371 glucose/galactose transporter
Iterative workflows. Iterative workflows. (A) A generic network reconstruction and model‐driven systems biology workflow is a cyclic path that iterates.
Glucose pulses incorporate directly into the de novo biomass in non‐dividing cells Glucose pulses incorporate directly into the de novo biomass in non‐dividing.
Perturbation of ligand depletion affects the ultrasensitivity of long‐term P‐Smad2 responses to different doses of TGF‐β stimulation. Perturbation of ligand.
(A) Observed significant protein fold‐changes during the fed–fasting transition in C57BL/6J (B6) and 129Sv (S9) mice fed with a normal diet (T0). (A) Observed.
Many of the diseases associated with high coevolution scores share genetic components. Many of the diseases associated with high coevolution scores share.
Inhibitory effect of perhexiline on the proliferation of the HepG2 cell line A, BPerhexiline was used to mimic the effect of the l‐carnitine analog on.
CNP520 treatment of male C57/BL6 mice for 8 weeks did not cause hair depigmentation CNP520 treatment of male C57/BL6 mice for 8 weeks did not cause hair.
AN12855 is efficacious in acute and chronic murine models of TB infection. AN12855 is efficacious in acute and chronic murine models of TB infection. (A,
Activity of a chemically modified miR-21 inhibitor in human bladder cancer xenografts. Activity of a chemically modified miR-21 inhibitor in human bladder.
Average trastuzumab serum concentrations in female minipigs following single subcutaneous administration of trastuzumab in formulations without and with.
In vivo tumor targeting and biodistribution of radiolabeled anti-CEA Fab-H-2Kb/ova conjugates. In vivo tumor targeting and biodistribution of radiolabeled.
Depletion of CD8+, CD4+, and Ly6G+ cells in subcutaneous TUBO tumor-bearing BALB/c mice treated with KM100 + MTX. Depletions were conducted by intraperitoneal.
Presentation transcript:

Validation of select PDN drug candidates in an in vivo endotoxemia model Validation of select PDN drug candidates in an in vivo endotoxemia model Therapeutic leads generated using PDN were directly tested for survival benefit using a murine model of endotoxemia. Select compounds were injected 24 h before and on the day of LPS administration, using routes and doses specified in the methods. C57bl/6 female mice were injected with a high‐lethality dose of Escherichia coli LPS (38–40 μg/g) followed by a subcutaneous injection of sterile saline. Significant differences in concentration between drug and vehicle‐treated pre‐ and post‐pubertal mice are labeled with ****P < 0.0001, ***P < 0.001, **P < 0.01, or *P < 0.05. Percent survival was compared using a log‐rank Mantel–Cox test. Rose B Joachim et al. Mol Syst Biol 2018;14:e7998 © as stated in the article, figure or figure legend