R-547 / Roche - LARVOL DELTA

Identification of effective cyclin-dependent kinase 3/cyclin E inhibitors using multi-level computational screening and simulation. (PubMed, Comput Biol Med) - "Docking studies identified interactions of the five selected candidates with crucial residues of CDK3. Global reactivity suggested favourable electronic properties for receptor binding. MD simulations, MM-PBSA and ONIOM revealed stable ligand-receptor interactions and favourable binding energetics. Extended 1200ns simulations of the two hits, CID_11212010 and CID_25211747, demonstrated exceptional stability of CID_25211747 with minimal conformational fluctuation. Additional ONIOM calculations reproduced the strong binding affinity of CID_25211747 with CDK3. Collectively, these results nominate CID_25211747 as a promising lead towards the development of effective CDK3 antagonists, offering valuable insight for future drug design."

Journal • Oncology • CDK3

CDK Inhibitor R547 Attenuates Pressure Overload-Induced Cardiac Hypertrophy via PI3K/AKT and TGF-β/Smad3 Signaling Pathways. (PubMed, J Cardiovasc Pharmacol) - "Mechanistically, R547 concurrently inhibited PI3K/AKT/mTOR hypertrophic signaling and TGF-β/Smad3 fibrotic pathways, with corresponding downregulation of ANP, BNP, β-MHC, and collagen I. This study identifies CDK-driven signaling as a nodal regulator of pressure overload cardiomyopathy. The dual inhibition of PI3K/AKT and TGF-β/Smad3 pathways by R547 demonstrates superior efficacy in mitigating both structural and functional deterioration, positioning it as a promising multifactorial therapy for cardiac hypertrophy."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertrophic Cardiomyopathy • Immunology • SMAD3 • TGFB1

Identification of potential drug targets for achalasia from genetic insights: a Mendelian randomization study. (PubMed, J Cardiothorac Surg) - "This study identifies potential drug targets for the treatment of different fractions and sites of AC, and these findings provide promising clues for more effective treatment of AC and have the potential to reduce drug development costs."

Journal • Gastrointestinal Disorder • Rare Diseases • BST2 • CD14 • CDK14 • IFIT1

Clinicopathologic and allele-specific analysis of germline ATM alterations in a pan-cancer cohort. (ASCO 2025) - P | "The most frequent mutations were: R2547_S2549del (n=17), K2756* (n=14) and V1268* (n=11)... Evaluation of a pan-cancer Pt population with ATM gPVs demonstrated a high prevalence of biallelic somatic inactivation. Most Pts with ATM gPVs who had malignancies implicated in ATM-associated cancer risk, had biallelic somatic inactivation in their tumors suggestive of their contribution to tumorigenesis. While biallelic ATM inactivation is associated with higher genomic instability, no enrichment in HRD phenotype was observed."

Clinical • Pan tumor • Ataxia • Genito-urinary Cancer • Immunology • Movement Disorders • Oncology • Pancreatic Cancer • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • ATM • BRCA1 • BRCA2 • CHEK2 • MUTYH

SYNERGISTIC EFFECTS OF ASXL1 AND BCOR ON HEMATOPOIESIS AND MDS/AML PROGRESSION (EBMT 2025) - "Next-generation sequencing (NGS) of bone marrow cells revealed the reappearance of the ASXL1 (p.G652S) mutation along with a newly identified BCOR truncating mutation (p.R1547*; c.4428+1G>A). After being treated with decitabine maintenance therapy, the patient achieved MDS remission, and no BCOR mutations were detected on day 286 post-transplantation... Based on these data, we hypothesize that the occurrence of BCOR mutations in the presence of ASXL1 mutations acts as a disease accelerator, impairing the normal development of hematopoietic cells and thereby promoting the onset and progression of MDS/AML. Clinical Trial Registry: No."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Developmental Disorders • Hematological Disorders • Myelodysplastic Syndrome • ASXL1 • BCOR • RAG1

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