cenisertib (AS703569) / Rigel Pharmaceuticals - LARVOL DELTA

Dissecting the binding landscape of four cKIT inhibitors through an integrated multifaceted approach. (PubMed, Int J Biol Macromol) - "We employed an integrated experimental and computational strategy to characterize the conformational landscape of cKIT and to elucidate the binding mechanisms of four inhibitors, Avapritinib, Olverembatinib, Labuxtinib and Cenisertib. While SPR indicates binding to both kinase states, LiP-MS, MD and X-Ray crystallography analyses reveal distinct interaction patterns depending on phosphorylation. Overall, this work highlights how distinct inhibitors exploit different conformational states of cKIT and demonstrates the value of integrating structural analyses, biophysical measurements, calculations and molecular simulations to define the mechanism of kinase inhibition."

Journal • Targeted Protein Degradation

Discovering novel ALK-lung carcinoma therapeutic strategies by identifying combinations with Alectinib from ALK-positive lung carcinoma cell lines (AACR 2024) - "Cells were characterized by bulk-RNAseq, bulk-DNA seq, Reverse-phase protein array, and Mass spectrometry to identify perturbed RNA pathways, DNA mutations, and proteome alterations. In this study, we present for the first time, a group of compounds, such as Gilteritinib, Trametinib, Dinaciclib, WYE-125132, Cenisertib, SN-38 which exhibit the capacity to induce cytotoxic effects in ALK-positive lung cancer cells, when combined with Alectinib. Through the integration of different multiomic approaches on five ALK-positive lung cancer cell lines, we have pinpointed a novel role of MAPK, CDK, and mTOR, pathways and their regulators, as a promising avenue for advancing treatment strategies for ALK-positive lung cancer. These findings, along with the identification of several other significant targetable elements illustrate a new approach towards the discovery of new drug combinations and targetable pathways to tackle ALK TKI resistance in ALK-positive patients before it..."

Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS • STAT3

Disulfidoptosis-related molecular subtypes and prognostic model for optimizing drug therapy in metastatic osteosarcoma patients. (PubMed, FASEB J) - "Six drugs targeting osteosarcoma metastasis were identified, with INF2-BP-1-102 and MEGF10-AS703569 showing the best docking scores, indicating their potential to treat OS metastasis effectively. These findings provide valuable insight into improving treatment for OS patients."

Biomarker • Journal • Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • INF2

Custo-Efetividade de Diferentes Tratamentos Minimamente Invasivos Para Disfunção Temporomandibular de Origem Articular sob a Perspectiva do Sistema Público de Saúde Brasileiro. (PubMed, Value Health Reg Issues) - "ARTRO plus dexamethasone acetate was considered the cost-effective technology, exhibiting higher net monetary benefit and higher acceptability from the SUS perspective."

Journal • Musculoskeletal Diseases • Pain • Rheumatology

A case of adult-onset localized recessive dystrophic epidermolysis bullosa, harboring the novel COL7A1 mutation p.G2754E and the previously reported mutation p.R1763. (PubMed, J Dermatol) - No abstract available

Journal

A Screening of Inhibitors Targeting the Receptor Kinase FERONIA Reveals Small Molecules that Enhance Plant Root Immunity. (PubMed, Plant Biotechnol J) - "Four representative inhibitors (reversine, cenisertib, staurosporine, and lavendustin A) inhibited the kinase activity of FER and its homologs in several crops by targeting the conserved ATP pocket in the kinase structure...Consistently, RNA sequencing assays showed that lavendustin A and reversine exert profound impacts on immunity-related gene expression. Our results will set a new milestone in the development of the plant RLK kinase regulation theory and provide a novel strategy for the prevention and control of plant soil-borne diseases without growth penalties."

Journal

Inhibition of Aurora Kinase B Is Important for Biologic Activity of the Dual Inhibitors of BCR-ABL and Aurora Kinases R763/AS703569 and PHA-739358 in BCR-ABL Transformed Cells. (PubMed) - "Experiments using drug resistant variants of Aurora B indicated that PHA-739358 acts on both, BCR-ABL and Aurora Kinase B, whereas Aurora kinase B inhibition might be sufficient for the anti-proliferative activity observed with R763/AS703569. Taken together, our data demonstrate that dual ABL and Aurora kinase inhibition might be used to overcome ABL TKI resistant CML."

Journal • Biosimilar • Hematological Malignancies • Oncology