Journal: MedComm

Article Title: Discovery of a First‐in‐Class Murine Double Minute 2‐Recruiting Positive Transcription Elongation Factor B PROTAC Degrader With Selective Antitumor Activity

doi: 10.1002/mco2.70723

Figure Lengend Snippet: MDM2‐ and p53‐dependent activities of MDM2‐recruiting P‐TEFb PROTAC degraders. (A) Effects of siRNA‐mediated MDM2 knockdown on cellular sensitivity to dCDK9‐010. Data were presented as mean ± standard deviation (SD); n = 3. (B) Effects of MDM2 knockdown on dCDK9‐010‐mediated CDK9/Cyclin T degradation. TC‐32 cells were transfected with indicated siRNAs for 48 h, followed by treatment with 2 µM dCDK9‐010 for 8 h. (C) MDM2 mRNA levels in wild type versus TP53 ‐knockout U87 cells, with or without compound treatment (2 µM, 8 h). Data were presented as mean ± SD ( n = 3); *** p < 0.001 based on one‐way analysis of variance (ANOVA); n.s., no significance. (D) Immunoblot analysis of P‐TEFb components, p53, and MDM2 in wild‐type and TP53 ‐knockout isogenic U87 cells after compound treatment (2 µM, 8 h). (E) Viability of isogenic U87 cells treated with dCDK9‐010. Data were presented as mean ± SD ( n = 3). (F) Immunoblot analysis of P‐TEFb components, p53, and MDM2 in NCI‐H226 and TC‐32 cells after siRNA‐mediated TP53 silencing and dCDK9‐010 treatment (2 µM, 8 h). (G) Effects of TP53 or MDM4 knockdown by siRNA relative to control on dCDK9‐010 sensitivity in NCI‐H226 and TC‐32 cells. Data were presented as mean ± SD ( n = 3).

Article Snippet: HEK293T (ATCC), TC‐32 (COG Repository, USA), HCT116 (ATCC), A549 (ATCC), HEPG2 (ATCC), HT1080 (ATCC), MDA‐MB‐231 (ATCC), U87 (U‐87MG, ATCC), U251 (U251MG, ATCC), and MKN45 (ATCC) cells lines were maintained in Dulbecco's modified Eagle medium (DMEM; Sigma‐Aldrich, Taufkirchen, Germany).

Techniques: Knockdown, Standard Deviation, Transfection, Knock-Out, Western Blot, Control

Journal: MedComm

Article Title: Discovery of a First‐in‐Class Murine Double Minute 2‐Recruiting Positive Transcription Elongation Factor B PROTAC Degrader With Selective Antitumor Activity

doi: 10.1002/mco2.70723

Figure Lengend Snippet: Selective activities of compounds 12 (dCDK9‐009) and 13 (dCDK9‐010) against TP53 wild‐type cancer cells. (A and B) Examination of dose‐dependent impacts of dCDK9‐009 and dCDK9‐010 in TP53 wild‐type HCT116, HT1080, NCI‐H460, and U87. Cells were treated with increasing concentrations of indicated compounds for 24 h. (C and D) Examination of impacts of dCDK9‐009 and dCDK9‐010 in non‐malignant HEK293T and mesenchymal stem cell line ASC52telo. Cells were treated with increasing concentrations of indicated compounds for 24 h. (E and F) Effect of dCDK9‐009 and dCDK9‐010 treatment on cellular viabilities of indicated cancer cell lines, as well as ASC52telo. IC 50 was presented as mean ± SD with three independent replicates. (G) Heatmap summarizing the IC 50 values of dCDK9‐009 and dCDK9‐010 across human cell lines tested in this study (related to E and F, Figures S3, S4, and S8).

Article Snippet: HEK293T (ATCC), TC‐32 (COG Repository, USA), HCT116 (ATCC), A549 (ATCC), HEPG2 (ATCC), HT1080 (ATCC), MDA‐MB‐231 (ATCC), U87 (U‐87MG, ATCC), U251 (U251MG, ATCC), and MKN45 (ATCC) cells lines were maintained in Dulbecco's modified Eagle medium (DMEM; Sigma‐Aldrich, Taufkirchen, Germany).

Techniques:

Journal: Nature Communications

Article Title: Iontronic click-to-release enables electrically controlled delivery of drugs and biomolecules beyond charge and size limitations

doi: 10.1038/s41467-026-70985-0

Figure Lengend Snippet: a Schematic of the synthesis and immobilization strategy for biotinylated CA4-prodrug ( 6 ), synthesized via sequential decoration of cTCO-bis-NHS ( 5 ). The biotin handle allows immobilization onto streptavidin-coated magnetic beads, forming a localized, iontronically activatable prodrug reservoir. IPs were positioned above the beads in a transwell insert containing U-87 cells in the lower chamber. Grey pills indicate inactive (bound) drug, blue (colored) pills indicate active drug. b 3D-printed platform designed to precisely position iontronic devices in standard 96-well transwell plates. c Cell viability of U-87 cells after operating iontronic devices delivering 1 for 4 h at +20 nA (Active, n = 8) and at −20 nA (Reverse, n = 7) into transwells holding CA4-immobilized beads from ( a ). Points represent individual biological replicates; bars indicate mean ± SD. GC growth control (untreated, n = 32), “No Beads” = operation of iontronic devices delivering 1 at +20 nA, no beads in transwell present ( n = 6), “No Tz 1 ” = CA4-immobilized beads in transwell present with iontronic delivery of K + (0.1 M KCl) instead of Tz 1 ( n = 8). Statistical analysis was done via a Brown–Forsythe and Welch ANOVA tests (one-way) and Dunnett’s T3 multiple comparisons test. α = 0.05. p -values: GC vs. No Beads (ns) = 0.2377; GC vs. No Tz 1 (ns) = 0.3827; GC vs. Reverse, 4 h (ns) = 0.5739, GC vs. Active, 4 h (****) = <0.0001. Certain graphical elements in ( a ) were created in BioRender. Hecko, S. (2026) https://www.BioRender.com/z8yr1eu .

Article Snippet: The human GBM cell line U-87 (provided by the MUG Cell Bank, catalogue no. 300367, CLS) was cultured at 37 °C and 5% CO 2 in Eagle’s minimum essential medium (E-MEM) containing 10% fetal bovine serum (FBS), 4.5 g/L glucose, 2 mM L -glutamine, and 1% MEM Non-Essential Amino Acids.

Techniques: Synthesized, Magnetic Beads, Control

Journal: Nature Communications

Article Title: Iontronic click-to-release enables electrically controlled delivery of drugs and biomolecules beyond charge and size limitations

doi: 10.1038/s41467-026-70985-0

Figure Lengend Snippet: a Schematic overview of the bioorthogonal click-to-release (C2R) cascade of CA4-prodrug: Aminoethyl tetrazine (Tz 1 ) triggers the release of the cytotoxic agent combretastatin A-4 ( CA4 ) from sulfo-cTCO-DMEDA-CA4 ( 4 ) via a tetrazine-triggered elimination from TCO caged payload and self-immolation. b Dose-dependent cell viability of human glioblastoma cell line U-87 after 72 h incubation with the key components of the C2R reaction. Data represent mean ± SD of n = 3 independent biological replicates. Curves were fit using four-parameter logistic regression. Prodrug 4 (0.01–1000 nM, grey curve); parent CA4 (0.01–1000 nM, blue curve); released CA4 (0.01–1000 nM 4 + 5 µM 1, dashed blue curve); Tz 1 (5 µM, purple data point). c Cell viability of U-87 cells after operating iontronic devices delivering 1 for 1 h at +20 nA (Active, n = 9) and at −20 nA (Reverse, n = 11). Points represent individual biological replicates; bars indicate mean ± SD. GC growth control (untreated, n = 12). Statistical analysis was done via a Brown–Forsythe and Welch ANOVA tests (one-way) and Dunnett’s T3 multiple comparisons test. α = 0.05. p -values: GC vs. Reverse, 1 h (ns) = 0.5339; GC vs. Active, 1 h (****) = <0.0001. Certain graphical elements in ( a ) were created in BioRender. Hecko, S. (2026) https://www.BioRender.com/z8yr1eu .

Article Snippet: The human GBM cell line U-87 (provided by the MUG Cell Bank, catalogue no. 300367, CLS) was cultured at 37 °C and 5% CO 2 in Eagle’s minimum essential medium (E-MEM) containing 10% fetal bovine serum (FBS), 4.5 g/L glucose, 2 mM L -glutamine, and 1% MEM Non-Essential Amino Acids.

Techniques: Incubation, Control