prmt5 inhibitor jnj  (MedChemExpress)

Journal: bioRxiv

Article Title: PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma

doi: 10.64898/2026.01.30.702866

Figure Lengend Snippet: a. Schematic of LUAD dedifferentiation spectrum, including the relative states of KP Early and KP Late . Each bar represents the general expression pattern of the given dedifferentiation state marker. b. Schematic of generation of PRMT5i-resistant variants of KP Late (KP1 36 ) and KP Early (KP2 36 ) cell lines. c. Dose response curves for KP Late (blue) and a representative KP Late -R line, KP Late -R1 (red) treated with JNJ-64619178 (PRMT5i) for 5 days. Data are mean ± SD of 3 technical replicates/line. p=0.0012, Welch’s t-test. d. GSEA results for gene sets listed in Supplementary Fig. 1c comparing KP Early and KP Late to their resistant lines. Color represents normalized enrichment score, while size inversely correlates with significance. e. Western blot of core LUAD dedifferentiation markers (Nkx2.1, Hnf4a, Hmga2) and Hsp90 loading control in KP Early and KP Late , as well as one control (DMSO selection) and three PRMT5i-resistant populations. f. UMAP of scRNA-seq dataset from an autochthonous KP model of LUAD with ( Left panel ) all clusters marked, ( Center panel ) Stmn2 expression, or ( Right panel ) Sox11 expression within the individual clusters. Cluster 12 (circled) was previously described to contain late-stage, pro-metastatic cells 44 .

Article Snippet: The PRMT5 inhibitor JNJ-64619178 was used for all PRMT5i treatment experiments and obtained from MedChemExpress (HY-101564).

Techniques: Expressing, Marker, Western Blot, Control, Selection

Journal: bioRxiv

Article Title: PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma

doi: 10.64898/2026.01.30.702866

Figure Lengend Snippet: a. Differentially accessible loci in KP Early after 5-day vehicle or 100nM PRMT5i treatment. Points represent individual loci that are more accessible (pink, p adj <0.01, log 2 FC>1), less accessible (blue, p adj <0.01, log 2 FC<-1), or not differentially accessible (gray). b. Cumulative fraction of the coefficient of variation for significant loci of KP Early after 5-day vehicle or PRMT5i treatment, indicating vehicle-derepressed (blue) and PRMT5i-derepressed (red) loci. p<10 -44 , F test. c. ChromVAR deviation score differences between vehicle- and PRMT5i-treated parental cells (x-axis) and resistant and parental cells (y-axis) for KP Early and KP Late . Points indicate differentially accessible (dark gray or colored, p adj <0.01) and not significant (light gray) motifs. Colored points represent motifs within the same TF family. d. Accessibility of indicated TF family motifs across: ( Top panel ) UMAP projections of a scATAC-seq dataset from an autochthonous model of LUAD, and ( Bottom panel ) chromVAR deviation scores for each biological replicate (n=3) of parental (blue), PRMT5i-treated parental (pink), and resistant (red) lines. e. Four categories of genome-wide representation of loci indicating derepression or repression of peak accessibility in response to a 5-day PRMT5i treatment of KP Early and whether this is established or not, in the stably-resistant KP Early -R1. ( Left panel ) Representative accessibility track, ( Center panel ) genome-wide accessibility heatmap, and ( Right panel ) all enriched TF motifs (p<10 -50 ) are shown. Colors denote: parental (blue), PRMT5i-treated parental (pink), and stable resistant (red) lines. f. Comparison of loci that show differentially accessible in response to a 5-day PRMT5i treatment of KP Early (drug-responsive) versus ones established in stably-resistant cells for ( Top panel ) KP Early and ( Bottom panel ) KP Late . Proportion of drug-responsive peaks that are also resistance state peaks is shown as a percentage. g. CTCF chromVAR deviation score in KP Early and KP Late treated with vehicle (blue) or PRMT5i for 5 days (pink). h. Genomic annotation of PRMT5-derepressed loci in KP Early and KP Late .

Article Snippet: The PRMT5 inhibitor JNJ-64619178 was used for all PRMT5i treatment experiments and obtained from MedChemExpress (HY-101564).

Techniques: Genome Wide, Stable Transfection, Comparison

Journal: bioRxiv

Article Title: PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma

doi: 10.64898/2026.01.30.702866

Figure Lengend Snippet: a. Schematic of the CDKN2A and adjacent MTAP loci indicating gene products and functions. b. Frequents of CDKN2A copy number losses in various tumor types, with SKCM (skin cutaneous melanoma) and LUAD highlighted. c. Schematic of effects of CDKN2A- deficiency on MTAP and PRMT5 biology. d. Normalized RNA expression counts for HMGA2 and RUNX2 in CDKN2A / MTAP -deficient LU99 cells treated with vehicle (blue) or MRTX1719 (red), an MTA-cooperative PRMT5i, for 3 or 5 days. Data are mean ± SD of 2 biological replicates/line. *p<0.05, **p<0.01, ***p<0.001, Student’s t-test. e-f. Differentially expressed genes comparing CDKN2A DKO to the rest of the tumors (+) in the TCGA LUAD ( e ) Firehose Legacy or ( f ) PanCancer cohorts. ( Left panel ) Points represent individual genes that have increased expression (red, p<0.05, log 2 FC>0.5) or decreased expression (blue, p<0.05, log 2 FC<-0.5). ( Right panel ) Expression of HMGA2 in indicated groups. Points represent individual patients with the total number of patients per group listed below the axis. p=0.00068 Legacy cohort and p=0.00003 PanCancer cohort, Student’s t-test.

Article Snippet: The PRMT5 inhibitor JNJ-64619178 was used for all PRMT5i treatment experiments and obtained from MedChemExpress (HY-101564).

Techniques: RNA Expression, Expressing

Journal: EMBO Molecular Medicine

Article Title: Isomeranzin activates Gnas-AMPK signaling to drive white adipose browning and curb obesity in mice

doi: 10.1038/s44321-025-00335-y

Figure Lengend Snippet: ( A ) Workflow diagram illustrating the process of obtaining thermogenic gene expression profiles associated with browning promotion from RNA-seq data in the GEO database, followed by the use of the CMap database to screen for small molecule compounds that promote browning. ( B ) Heatmap of the top 100 upregulated genes from four RNA-seq datasets. The remaining 100 genes are listed in Table . ( C ) Venn diagram of the four small molecule compound sets identified. ( D ) Representative immunoblot of Ucp1 protein in primary inguinal adipocytes treated with ten candidate small molecule compounds. Rosiglitazone is used as a positive control for adipose browning promotion. ( E ) Relative mRNA expression levels of Ucp1 in primary inguinal adipocytes treated with ten candidate small molecule compounds ( n = 3). Control vs. AS-601245, p = 0.9610; Control vs. AT-7519, p = 0.0015; Control vs. BMS-345541, p = 0.9888; Control vs. CGP-60474, p = 0.9994; Control vs. ER-27319, p < 0.0001; Control vs. JNJ-7706621, p < 0.0001; Control vs. Alvocidib, p = 0.0170; Control vs. Daunorubicin, p = 0.0004; Control vs. Isomerazin, p < 0.0001; Control vs. Pirarubicin, p < 0.0001. ( F ) Relative mRNA expression levels of Fabp4 in primary inguinal adipocytes treated with ten candidate small molecule compounds ( n = 3). Control vs. AS-601245, p = 0.9974; Control vs. AT-7519, p = 0.0017; Control vs. BMS-345541, p = 0.9975; Control vs. CGP-60474, p = 0.0002; Control vs. ER-27319, p = 0.0005; Control vs. JNJ-7706621, p < 0.0001; Control vs. Alvocidib, p = 0.0032; Control vs. Daunorubicin, p < 0.0001; Control vs. Isomerazin, p = 0.9995; Control vs. Pirarubicin, p < 0.0001. n presents biological replicates. Data are presented as mean ± SEM. Statistical test: one-way ANOVA followed by Dunnett’s multiple comparisons test. Statistical significance is indicated as follows: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, and ns indicates no significant difference. .

Article Snippet: JNJ-7706621 , MedChemExpress , HY-10329.

Techniques: Gene Expression, RNA Sequencing, Western Blot, Positive Control, Expressing, Control

Journal: Advanced Science

Article Title: Stromal Cell‐Mast Cell Communication Orchestrates Anti‐Viral Immunity in the Meninges

doi: 10.1002/advs.202514842

Figure Lengend Snippet: Meningeal stromal cell‐derived IL‐33 and ATP coordinate antiviral defense. A) Maximal intensity projection of dural meninges stained for stromal cells (green), IL‐33 (red), LCMV (white) and nuclei (blue) at 6 dpi. Scale bar, 2000 µm (left, whole mount); 100 µm (right). n = 6 (mice). B) The density of meningeal IL‐33 + stromal cells (A). n = 20 (clusters, from 6 mice). C–H) Primary meningeal stromal cells were cultured. C) Staining of IL‐33 (red), nuclei (blue), and LCMV (white) post LCMV infection. MOI = 2:1. Scale bar, 200 µm. n = 6–7 (views). D) The percentage of IL‐33 high cells (C). E) The percentage of IL‐33 high cells treated with medium alone (NC), LCMV, LCMV + 2‐APB at 1 dpi. MOI = 1:1. n = 25‐28 (views). F) The percentage of IL‐33 high cells treated with medium alone (NC), or ionomycin + PMA for 1 day. n = 24‐36 (views). G) Heatmap of differentially expressed genes at 1 dpi. MOI = 2:1. n = 3 (wells, each well from 2 mice). H) The extracellular ATP level after LCMV infection. MOI = 2:1. n = 2‐3 (wells, each well from 2 mice). I) Live cell imaging of calcium flux in PCMCs from Tpsb2‐CreERT2; Ai162 fl/+ mice stimulated with conditioned medium from virus‐infected stromal cells. Scale bar, 50 µm. n = 75–275 (cells). J) Quantification of (I). K) Live cell imaging of calcium flux in BMMCs from Tpsb2‐CreERT2; Ai162 fl/+ mice stimulated with IL‐33, ATP, or ionomycin + PMA. Scale bar, 50 µm. n = 156‐356 (cells). L) Quantification of (K). M) Live cell imaging of calcium flux in the meninges from Tpsb2‐CreERT2; Ai162 fl/+ mice with the stimulation of ATP ex vivo . Scale bar, 200 µm. n = 33 (cells). N) Quantification of (M). O) Meningeal immune cell subset counts treated with ATP receptor antagonist (AZD9056, JNJ55308942, suramin sodium salt) at 6 dpi. n = 7–8 (mice). Data are presented as mean ± SEM and p values were calculated by two‐tailed, paired Student's t ‐test (B), two‐tailed, unpaired Student's t ‐test (D–F, H, O), Wald test from DESeq2 (G).

Article Snippet: For ATP receptor blockade experiments, mice received intraperitoneal injections of 12.5 mg kg −1 AZD9056 (MCE, HY‐19427A), 12.5 mg kg −1 JNJ‐55308942 (MCE, HY‐123857), or 20 mg kg −1 suramin (MCE, HY‐B0879A) on days 1, 3, and 5 post‐infection.

Techniques: Derivative Assay, Staining, Cell Culture, Infection, Live Cell Imaging, Virus, Ex Vivo, Two Tailed Test