R-547 / Roche - LARVOL DELTA

Identification of C/EBPδ-Modifying Compounds as Potential Anticancer Agents Using a High-Throughput Drug Screen. (PubMed, J Cell Mol Med) - "We confirmed the potential importance of cell cycle-mediated regulation of C/EBPδ by showing that four of the most potent C/EBPδ activators-R547, PHA793387, AZD5438 and AT7519, all multi-cyclin-dependent kinase (CDK) inhibitors-limited the clonal expansion of PDAC cells. Next to providing a valuable selection of C/EBPδ-modulating compounds for the use in preclinical studies, this report contributes to our understanding of the molecular regulatory mechanisms of C/EBPδ in general and in PDAC in particular."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CEBPD

Identification of New Substrates of ExoS from Pseudomonas aeruginosa (ASM Microbe 2024) - "One of the known substrates, Ezrin, was detected, with modifications occurring on R542 and R547...These results show an expanded ExoS ADP-ribosylome compared to prior studies on 16 known substrates. Using this data set, future work may determine the mechanism for ExoS-mediated effects currently unattributed to known substrates."

CASP4 • EZR • MYH9 • NLRP3

Ectopic Expression of Gastrodia Antifungal Protein in Rice Enhances Resistance to Rice Sheath Blight Disease. (PubMed, J Fungi (Basel)) - "Two versions, with or without a signal peptide, for each of the four GAFP genes were introduced into XD3 and R6547 rice cultivars, and all transgenic lines displayed stronger ShB resistance than the corresponding wild-type control in both greenhouse and field conditions...We also evaluated the agronomic traits of these transgenic rice and found that ectopic expression of GAFPs in rice at appropriate levels did not affect agronomic traits other than enhancing ShB resistance. Together, these results indicate that GAFP genes, especially GAFP2, have great potential in rice breeding against ShB disease."

Journal

EFFECT OF DIALYSIS MODALITY AND MEMBRANE PERMEABILITY ON FGF 23 LEVEL AND CARDIOVASCULAR CALCIFICATION IN ESRD PATIENTS (ISN-WCN 2023) - "Serum FGF23 post-HD and HDF had significant positive correlation with serum Calcium (r=0.659, P=0.002), (r=0.474, P=0.035), PTH (r=0.485, P=0.03), (r=547, P=0.013) and CRP (r=0.646, P=0.002), (r=707, P<0.001) and serum Phosphorus (r=0.462, P=0.04), (r=478, P=0.033) respectively...Group 1 Group 2 P value Pre Mean ± SD 868.80 ± 321.52 897.20 ± 285.24 0.325 Range 100 - 500 500 - 1600 Post Mean ± SD 323.60 ± 79.16 176.00 ± 91.47 <0.001* Range 200 - 450 100 - 500 Reduction ratio (%) Mean ± SD 58.28% ± 15.60% 79.98% ± 8.28% <0.001* Range 20.00% - 80.00% 54.55% - 89.57% *: significant as p value < 0.05. Open table in a new tab Conclusions Using online HDF technique showed a significant reduction of FGF23 and improvement of carotid intima-media thickness calcification score."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Renal Disease • FGF23

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets. (PubMed, Clin Epigenetics) - "Multiple associations indicate potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggest targets for combination therapies. While many correlations were not specific to SCLC lineages, several lineage markers were associated with specific agents."

IO Biomarker • Journal • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • ATR • EPAS1 • EPHA2 • EZH2 • SLFN11 • STING • YAP1

The effect of R547, a cyclin-dependent kinase inhibitor, on hepatocellular carcinoma cell death. (PubMed, Turk J Biol) - "The early apoptotic rates of 38% and 45% (P < 0.05 for both) after applications of 10 and 25 μM R547 (control: 4.1%), respectively, indicated that R547 has an apoptotic effect on H-4-II-E cells in 24 h. The apoptosis morphology at 24 h of treatment was clearly observed with microscopic examinations. According to our results, it is obvious that R547 has antiproliferative action when compared to cisplatin."

Journal

Cyclin-dependent kinase inhibitors AZD5438 and R547 show potential for enhancing efficacy of daunorubicin-based anticancer therapy: interaction with carbonyl-reducing enzymes and ABC transporters. (PubMed, Biochem Pharmacol) - "In conclusion, we propose AZD5438 and R547 as modulators of DAUN resistance that can prevent AKR1C3-mediated DAUN biotransformation to DAUN-OL. This interaction could be beneficially exploited to prevent failure of DAUN-based therapy as well as the undesirable cardiotoxic effect of DAUN-OL."

Clinical • Journal

Antifungal Activity of Beauveria bassiana Endophyte against Botrytis cinerea in Two Solanaceae Crops. (PubMed, Microorganisms) - "A high antifungal effect was observed, and strains RGM547 and RGM644 showed the lowest percentage of the surface affected by the pathogen. Native strains of B. bassiana colonized tomato and chili pepper tissues and provided important levels of antagonism against B. cinerea."

Journal

Associations of epigenome-wide DNA methylation patterns with chemosensitivity and chemoresistance of small cell lung cancer cell lines (AACR-NCI-EORTC 2019) - "Increased methylation and low expression of TREX1 were associated with SCLC cell line sensitivity to multiple Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901, as well as to the CDK inhibitor R-547, Vertex ATR inhibitor Cpd 45, and the mitotic spindle disruptor vinorelbine...Among other examples, EPAS1 (HIF2A) was associated with several Aurora kinase inhibitors, the PLK1 inhibitor GSK-461364, and the Bcl-2 inhibitor ABT-737...IGFBP5, which is expressed in the tuft cell-like SCLC subtype, was associated with the mTOR inhibitor INK-128...Methylation and expression of YAP1, a SCLC lineage driver regulating the Hippo pathway, were correlated with the MTOR inhibitor rapamycin...The 5’ UTR region of the epigenetic modifier EZH2 was associated with Aurora kinase inhibitors and the FGFR inhibitor BGJ-398. These and multiple other associations identified in this study provide a novel understanding of epigenetic mechanisms which may modulate SCLC response to..."

IO Biomarker • Preclinical • EPAS1 • EPHA2 • EZH2