ku55933  (MedChemExpress)

Journal: NAR Cancer

Article Title: EXO1 inhibition selectively kills replication repair-deficient cancer cells

doi: 10.1093/narcan/zcag029

Figure Lengend Snippet: (A ) Survival of eHAP iCas9 wild-type cells with either sgNT or sg FANCG following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 0.15 μM PARP inhibitor olaparib; ordinary two-way ANOVA with Tukey’s test. ( B ) Survival of eHAP iCas9 wild-type cells with either sgNT or sg ZRSR2 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 0.15 μM PARP inhibitor olaparib; ordinary two-way ANOVA with Tukey’s test. ( C ) Survival of eHAP iCas9 wild-type cells with either sgNT or sg BRCC3 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 0.15 μM PARP inhibitor olaparib; ordinary two-way ANOVA with Tukey’s test. ( D ) Survival of eHAP iCas9 wild type cells with either sgNT or sg APITD1 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 0.15 μM PARP inhibitor olaparib; ordinary two-way ANOVA with Tukey’s test. ( E ) Survival of eHAP iCas9 wild type cells with either sgNT or sg FANCG following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 3 μM PARP inhibitor veliparib; ordinary two-way ANOVA with Tukey’s test. ( F ) Survival of eHAP iCas9 wild type cells with either sgNT or sg ZRSR2 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 3 μM PARP inhibitor veliparib; ordinary two-way ANOVA with Tukey’s test. ( G ) Survival of eHAP iCas9 wild type cells with either sgNT or sg BRCC3 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 3 μM PARP inhibitor veliparib; ordinary two-way ANOVA with Tukey’s test. ( H ) Survival of eHAP iCas9 wild type cells with either sgNT or sg APITD1 following KO induction after 5-day treatment with either ART5537 alone or ART5537 with 3 μM PARP inhibitor veliparib; ordinary two-way ANOVA with Tukey’s test. ( I ) Survival of eHAP iCas9 wild type, FANCG KO and ZRSR2 KO cells after 5-day treatment with either ART5537 alone or ART5537 with 0.15 μM PARP inhibitor olaparib; ordinary two-way ANOVA with Tukey’s test.

Article Snippet: Compounds developed for EXO1 inhibition [compound 20, compound 29 (ART5537), and compound 30] [ ] were a generous gift from Artios Ltd, while ATM inhibitor (KU-55933), PARP inhibitor olaparib (AZD2281), PARP inhibitor veliparib (ABT-888), and TYMS inhibitor Pemetrexed ( LY231514 ) were purchased from Selleckchem.

Techniques:

Journal: bioRxiv

Article Title: Tobacco Carcinogen Induces Persistent DNA Damage and Homologous Recombination Dysregulation in Pancreatic Ductal Carcinogenesis

doi: 10.64898/2026.10.13.758888

Figure Lengend Snippet: (A ) Quantification of γH2AX foci per nucleus in H6c7 cells following NNK treatment, with and without the ATM inhibitor KU55933 (10 μmol/L). Data are mean ± SEM from three independent experiments; significance was determined by two-way ANOVA. ( B ) Time course of γH2AX foci–positive cells (%) over 72 hours following NNK treatment, with or without KU55933 (10 μmol/L). Data are mean ± SEM. ( C ) Subcellular fractionation western blot showing nuclear and cytoplasmic RAD51, Histone H3, and STAT3 protein levels in H6c7 cells following increasing NNK concentrations (0–10 μmol/L). ( D ) Co-immunofluorescence of BRCA2 and RAD51 in H6c7 cells following 50-day NNK treatment, demonstrating enhanced nuclear co-localization of RAD51 and BRCA2. Data are mean ± SEM; significance determined by Student’s t -test (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001). ( E ) Quantification of RAD51 foci per cell in H6c7 cells treated with NNK, with or without KU55933 (10 μmol/L). Data are mean ± SEM.

Article Snippet: For ATM inhibition experiments, the selective ATM kinase inhibitor KU55933 (Selleckchem, catalog no. S1092) was dissolved in DMSO and used at a final concentration of 10 μmol/L.

Techniques: Cell Fractionation, Western Blot, Immunofluorescence

Journal: Clinical and Translational Medicine

Article Title: ROS‐ATM‐CBP axis‐mediated PARP1 lactylation aggravates doxorubicin‐induced cardiotoxicity

doi: 10.1002/ctm2.70745

Figure Lengend Snippet: ROS‐ATM‐CBP signalling pathway activates PARP1 lactylation. (A, B) Intracellular ROS and lactate levels in HL‐1 cells treated with 1 µM doxorubicin for 0, 2 and 4 h. (C) Representative immunoprecipitation, western blots and quantification for detecting PARP1 lactylation. HL‐1 cells were stimulated by doxorubicin (1 µM for 0, 2 and 4 h), and the cells were lysed and immunoprecipitated using an anti‐PARP1 antibody, followed by detection of Pan‐KLA. (D) Schematic of the effect of SIRT1 activation on the lactylation level of PARP1 in mice. DOX (5 mg/kg) or the same volume of saline was administered intraperitoneally once weekly. One week before the DOX treatment, mice were pre‐treated with resveratrol (SIRT1 activator, 10 mg/kg/day) via daily intraperitoneal injections. (E) The SIRT1 activity was detected. (F–H) Representative immunoprecipitation, western blots and quantification for detecting PARP1 lactylation and protein expression of SIRT1. (I) Schematic of the effect of CBP inhibition on the lactylation level of PARP1 in mice. DOX (5 mg/kg) or the same volume of saline was administered intraperitoneally once weekly. One week before the DOX treatment, mice were pre‐treated with SGC‐CBP30 (CBP inhibitor, 15 mg/kg/day) via daily intraperitoneal injections. (J) The CBP activity was detected. (K–M) Representative immunoprecipitation, western blots and quantification for detecting PARP1 lactylation and protein expression of CBP. (A–C) Based on the central limit theorem, the data were considered to be normally distributed. Relative protein levels were calculated as fold changes vs the first group. Data are presented as mean ± SD. Statistical significance was assessed by one‐way ANOVA with Tukey multiple comparisons test ( P values adjusted for 3 comparisons). (D–M) Relative protein levels were calculated as fold changes vs. the first group. Data are presented as mean ± SD. Statistical significance was assessed by two‐way ANOVA with Bonferroni multiple comparisons test ( p ‐values adjusted for 9 comparisons). ns p > .05, * p < .05, ** p < .01, *** p < .001.

Article Snippet: ATM inhibitor (KU‐55933; #HY‐12016; 10 μM; 2 h); LDHA inhibitor (Galloflavin; #HY‐W040118; 10 −5 M; 24 h) and CBP activator (CTB; #HY‐134964; 10 −4 M; 24 h) were obtained from MedChemExpress.

Techniques: Immunoprecipitation, Western Blot, Activation Assay, Saline, Activity Assay, Expressing, Inhibition

Journal: Clinical and Translational Medicine

Article Title: ROS‐ATM‐CBP axis‐mediated PARP1 lactylation aggravates doxorubicin‐induced cardiotoxicity

doi: 10.1002/ctm2.70745

Figure Lengend Snippet: Model showing the molecular signalling cascade of CBP‐PARP1 lactylation–PARylation axis. The schematic depicts how oxidative stress‐induced ROS activates the ATM‐CBP‐PARP1 signalling pathway via a lactylation–PARylation cascade to promote cardiomyocyte apoptosis.

Article Snippet: ATM inhibitor (KU‐55933; #HY‐12016; 10 μM; 2 h); LDHA inhibitor (Galloflavin; #HY‐W040118; 10 −5 M; 24 h) and CBP activator (CTB; #HY‐134964; 10 −4 M; 24 h) were obtained from MedChemExpress.

Techniques: