Inhibition of CDK9 by UNC drives MYC loss.

Slides:

Advertisements

Similar presentations

Demonstrations I, II, and III.

Advertisements

Cytotoxicity of MSP samples to normal and cancer cell lines.

Nuclear calcium signaling drives nuclear actin polymerization in T cells. Nuclear calcium signaling drives nuclear actin polymerization in T cells. (A)

Nuclear Arp3 mediates formation of TCR-induced nuclear actin filaments

Three different types of transfer functions with a codomain of [0,1].

Histology results comparing surgical and naïve groups.

T2-weighted cross-sectional MR imaging of MSP swarms inside SD rats.

Inhibition of macropinocytosis activates the TFEB-TRPML1 axis.

Group data during free walking between sessions 1 and 16.

Arp2/3-mediated formation of nuclear actin networks is essential for CD4+ T cell effector functions. Arp2/3-mediated formation of nuclear actin networks.

Platelets are required for hFcγRIIA-induced anaphylaxis.

Tukey boxplots overlaid on data points from objective and subjective measures, displaying results from study 1. Tukey boxplots overlaid on data points.

T-bethi MP cells produce IFN-γ in response to IL-12.

Differentiation of AZD4785 from MAPK pathway inhibitors in vitro

Tactile features for prosthesis perception.

BAP1 deficiency results in thymic atrophy and loss of thymocyte populations. BAP1 deficiency results in thymic atrophy and loss of thymocyte populations.

Fig. 4 Altitudinal distributions of ice thickness change (m year−1) for the 650 glaciers. Altitudinal distributions of ice thickness change (m year−1)

AMPK-mediated mTORC2 signaling does not require mTOR Ser1261phosphorylation. AMPK-mediated mTORC2 signaling does not require mTOR Ser1261phosphorylation.

AMPK directly increases mTORC2 catalytic activity.

LIMK1 inhibition protects against Aβ-induced neuronal hyperexcitability. LIMK1 inhibition protects against Aβ-induced neuronal hyperexcitability. (A) Representative.

Cell viability tests. Cell viability tests. SEM images of (A) MC3T3-E1 cells and (B) MSCs on days 1, 3, and 5 of culture. (C) Survival rates of MC3T3-E1.

Experimental characterization of the milliDelta’s quasi-static workspace (yellow) compared with the theoretical workspace (blue) generated by the kinematic.

T2-weighted cross-sectional MR imaging of MSP swarms inside SD rats.

Fig. 5 Thermal conductivity of n-type ZrCoBi-based half-Heuslers.

Microrobots with different cell-carrying capacities under different grid lengths (lg) and burr lengths (lb). Microrobots with different cell-carrying capacities.

Immune evasion occurs through loss of TNF, IFN-γ, or antigen presentation pathways. Immune evasion occurs through loss of TNF, IFN-γ, or antigen presentation.

Fig. 2 Reference-fixing experiment, results.

Global analysis of RV[S/T]F motif phosphorylation during mitosis.

PLI and PLIII are activating ligands for MR1Ts.

Optimization of a MYC degradation screen.

Fig. 3 NK cells are enriched in ICB-sensitive tumors in mouse models and patients and are required for response. NK cells are enriched in ICB-sensitive.

MYC degradation screen identifies a compound that stabilizes MYC protein. MYC degradation screen identifies a compound that stabilizes MYC protein. (A)

Fig. 3 Rotation experiment, setup.

Fig. 1 Product lifetime distributions for the eight industrial use sectors plotted as log-normal probability distribution functions (PDF). Product lifetime.

Fig. 3 BMS blocks functional responses in primary immune cells driven by IL-23 and IL-12. BMS blocks functional responses in primary immune.

Drug response profiles and experimental validation.

Fig. 1 Distribution of total and fake news shares.

In vitro cell-release experiments on a glass substrate.

Fig. 6 RUNX/CBFB interaction inhibitor, Ro5-3335, significantly decreases mouse neurofibroma growth in vivo. RUNX/CBFB interaction inhibitor, Ro5-3335,

Fig. 1 Impacts of intensified acidification on stream pH and calcium concentration. Impacts of intensified acidification on stream pH and calcium concentration.

Sensitivity analysis of cellular responses to perturbation of the DNA damage response signaling in the presence of chemotherapies. Sensitivity analysis.

Fig. 6 WPS imaging of different chemical components in living cells.

Fig. 4 Cdc42 enhances the cellular uptake of EVs.

Fig. 5 Simultaneous absence of caspase-3 and -7 is required for significant decrease of caspase-8 and -9 activation in intrinsic apoptosis. Simultaneous.

Galloping-like gait with the design of a two-legged robot.

AEGIS autonomous targeting process.

Fig. 3 ET dynamics on the control and treatment watersheds during the pretreatment and treatment periods. ET dynamics on the control and treatment watersheds.

Fig. 2 Results of the learning and testing phases.

Fig. 3 Production of protein and Fe(II) at the end of growth correlated with increasing concentrations of ferrihydrite in the media that contained 0.2.

Pharmacological targeting of CDs promotes response to KRASG12C inhibition in vivo. Pharmacological targeting of CDs promotes response to KRASG12C inhibition.

Fig. 2 NH3, NOx, SO2, and NMVOC emission changes triggered by the JJJ clean air policy. NH3, NOx, SO2, and NMVOC emission changes triggered by the JJJ.

Immune evasion occurs independently of perforin-mediated killing.

Fig. 2 Top 10 countries, ecoregions, conservation hotspots, and KBAs with the largest area of restoration hotspots. Top 10 countries, ecoregions, conservation.

CDs with KRASG12C cooperatively sustain downstream signaling outputs to promote survival and proliferation. CDs with KRASG12C cooperatively sustain downstream.

Combination therapies targeting CDs with KRASG12C differ in their ability to promote S-IIP target engagement. Combination therapies targeting CDs with.

Initial testing and characterization of cAMPr in ES cells.

UNC drives MYC protein loss.

Fig. 4 CO2 emission changes triggered by the JJJ clean air policy.

Fig. 6 Stabilization of hippocampal signaling over sleep.

Fig. 3 Effects of ASO and eGLP1-ASO conjugates on gene expression and protein levels in vitro in cell lines and primary mouse islet cells. Effects of ASO.

Fig. 3 Comparisons of NDVI trends over the globally vegetated areas from 1982 to Comparisons of NDVI trends over the globally vegetated areas from.

Fig. 4 A novel peptidomimetic (AV3) against ITGA5.

Acute circadian disruption alters ILC3 cytokine secretion.

REV-ERBα deficiency reduces frequency and number of NKp46+ ILC3s.

Afatinib rapidly destabilizes endogenous TRIB2 and specifically induces caspase 3 cleavage and U937 cytotoxicity. Afatinib rapidly destabilizes endogenous.

Fig. 1 Spatial and cartilage depth-related distributions of deamidated proteins in human adult cartilage. Spatial and cartilage depth-related distributions.

Fig. 3 Gene expression analysis in 48-plex drug treatment experiments.

Fig. 2 Speaker-independent speech separation with ODAN.

Fig. 3 Calculated electronic structure of ZrCoBi.

Fig. 5 Treatment with molecules 13, 14, and 15 decreases HIV-1 R5 infection in human macrophages. Treatment with molecules 13, 14, and 15 decreases HIV-1.

Presentation transcript:

Inhibition of CDK9 by UNC10112785 drives MYC loss. Inhibition of CDK9 by UNC10112785 drives MYC loss. (A) MIA PaCa-2 cells were treated for 1 hour with different concentrations UNC10112785, after which they were lysed and applied to the MIBs column. Kinases were eluted from the column and identified and quantified by LC/MS as described in Materials and Methods. Bars to the left of center line indicate kinases reduced after compound addition. Data are from one experiment, which served to identify hits to validate with reproducibility and explore further. (B) MIA PaCa-2 cells were treated with UNC10112785, and CDK8/19 inhibition was measured by the abundance of phosphorylated STAT1 (pSTAT1). (C and D) MIA PaCa-2 cells were treated with the indicated compounds for 6 hours, and CDK8/19 or CDK9 inhibition was measured by pSTAT1 (C) and pPol II (D). (E) MIA PaCa-2 cells were treated for 72 hours with the indicated compounds, and cell proliferation was measured by cell count, normalized to that cells treated with the vehicle control (DMSO). 2D, two-dimensional. (F) MIA PaCa-2 cells suspended in 3% agarose were treated for 72 hours with the indicated compounds, and cell proliferation was measured by alamarBlue, normalized to cells treated with vehicle (DMSO). All data are representative of at least three independent experiments unless otherwise indicated. Data in (E) and (F) are presented as means ± SD. Devon R. Blake et al., Sci. Signal. 2019;12:eaav7259 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works