kinase inhibitor library screening epigenetics drug library  (Selleck Chemicals)

Journal: International Journal of Biological Sciences

Article Title: ARID1A deficiency activates OSM-STAT3 axis in endometrial cancer, creating vulnerability to JAK/STAT3 inhibition

doi: 10.7150/ijbs.129142

Figure Lengend Snippet: Identification of synthetic lethality of ARID1A and JAK/STAT3 in endometrial cancer through drug library screening. A. Schematic illustration of the synthetic lethality screenings with the Epigenetics Drug Library and the Kinase Inhibitor Library. B. Immunoblot analysis showing ARID1A knockout in A1 and B7 single clone. C. Drugs with selectivity index (SI)≥2 were selected as synthetic lethality candidates. SI=IC50 ARID1A+/+ /IC50 ARID1A-/- . D. Synthetic lethality in HEC1B-ARID1A -/- cell treated with stattic (D, F) and gandotinib (E, G) for 72h. The cell images were taken with IncuCyte ZOOM. Scale bar, 300 μm. H. Immunoblot analysis validated the ARID1A overexpression in HEC1B-ARID1A -/- cell. I. Overexpressed ARID1A rescued the synthetic lethality mediated by stattic. Data are mean±sd. * P <0.05, ** P <0.01. J-K. HEC1B ARID1A isogenic cell pair were transfected with STAT3-siRNA for 72 h. J. The quantitative analysis of synthetic lethality induced by STAT3-siRNA. Data are mean±sd. *** P <0.001. K. The growth curve of HEC1B ARID1A isogenic cell pair treated with STAT3-siRNA. **** P <0.0001. Two-way ANOVA test. L- N. IC50 test treated with stattic and gandotinib in endometrial cancer cell line. Data are mean±sd. * P <0.05.

Article Snippet: Epigenetics Drug Library and the Kinase Inhibitor Library screening were purchased from Selleck Chemicals.

Techniques: Drug discovery, Western Blot, Knock-Out, Over Expression, Transfection

Journal: NPJ Precision Oncology

Article Title: Lestaurtinib’s antineoplastic activity converges on JAK/STAT signaling to inhibit treatment naïve and therapy resistant forms ovarian cancer

doi: 10.1038/s41698-025-00947-0

Figure Lengend Snippet: a Viability of indicated cell lines following 48 h of treatment with 1 µM of the 145 compounds contained in the Cayman Chemical epigenetic drug library (#11076) relative to DMSO vehicle. N = 2. b Drug screen hit prioritization schema. Figure created with BioRender.com. c Dose response curves (two-fold dilution starting at 2.5 µM) and IC50 concentrations for lestaurtinib in a panel of therapy-sensitive and -resistant ovarian cancer cell lines following 5–10 days of treatment. N = 8. Graphs represent mean ± standard error. Abbreviations: Cis Res cisplatin-resistant, Olap R olaparib-resistant.

Article Snippet: Fig. 1 Identification of lestaurtinib as a novel inhibitor of therapy-sensitive and -resistant ovarian cancer cells. a Viability of indicated cell lines following 48 h of treatment with 1 μM of the 145 compounds contained in the Cayman Chemical epigenetic drug library (#11076) relative to DMSO vehicle.

Techniques: Drug discovery

Journal: Nucleic Acids Research

Article Title: Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing

doi: 10.1093/nar/gkae570

Figure Lengend Snippet: Overview of the reporter system and screen data. ( A ) Heatmap of the chromatin landscape at the integration sites of the integrated pathway reporters (IPRs) in K562 clone #5 used in this study. Z -scores of 25 chromatin features are indicated for all 19 IPRs. Chromatin features are colored by their type, and IPRs are clustered into chromatin groups based on the chromatin features. IPRs in bold are the two example IPRs depicted in B. Adapted from . ( B ) Left panel: genomic locations of the IPRs, colored by their associated chromatin group. Right panel: indel frequency distributions (in the absence of drug treatment) of two representative IPRs, one in euchromatin (IPR5), and one in heterochromatin (IPR7). ( C ) Number of drugs per target group in the screen. HDAC = histone deacetylase, JAK = Janus kinase, AurK = aurora kinase, PARP = poly (ADP-ribose) polymerase, ERD = epigenetic reader domain, HMT = histone methyltransferase, PIM = proviral integration site for moloney murine leukemia virus kinase, HDM = histone demethylase, DNMT = DNA methyltransferase, HAT = histone acetyltransferase and HIF = hypoxia inducible factor. ( D ) Schematic overview of the experimental layout and the readouts of the drug screen.

Article Snippet: For the drug addition, we combined two 96-well epigenetic drug screening libraries from two commercially available libraries from Selleck Chemicals and Enzo Life Sciences (for list of drugs see ).

Techniques: Histone Deacetylase Assay, Virus