AT13148 / Otsuka - LARVOL DELTA

The Compound AT13148 Targeting AKT Suppresses Dengue Virus 2 Replication. (PubMed, Vector Borne Zoonotic Dis) - " The findings indicate that AT13148 effectively targets the AKT pathway, demonstrating potential as an antiviral therapeutic against DENV-2 by interfering with the virus's post-entry processes. Further in vivo studies are warranted to assess the efficacy of AT13148 in controlling DENV infection."

Biomarker • Clinical • Clinical guideline • Clinical protocol • Journal • Observational data • Retrospective data • Review • Dengue Fever • Infectious Disease

Regulation of reactive oxygen molecules in pakchoi by histone acetylation modifications under Cd stress. (PubMed, PLoS One) - "In this work, we investigated this issue using Cd-stressed pakchoi seedlings treated with six epi-modification inhibitors (5-AC, RG108, TSA, CUDC101, AT13148, and H89) as experimental materials. Also, TSA addition at high concentrations could also increase Cd-induced ROS accumulation. Based on this, we propose that the ROS molecular pathway may be related to epigenetic regulation, and chromatin modification may affect ROS accumulation by regulating gene expression, providing a new perspective for studying the regulatory mechanism of epigenetic modification under abiotic stress."

Epigenetic controller • Journal

Targeted investigational oncology agents (IOA) in the NCI60: a phenotypic systems-based resource (AACR 2023) - "Only 3 of 15 AKT inhibitors in the IOA set are not found in the connected cluster with a COMPARE correlation of 0.7 including the multi-kinase inhibitors perifosine and AT-13148. The AKT cluster includes both allosteric (MK-2206) and competitive inhibitors highlighting the NCI60 is a functional cell assay...The mTOR inhibitors (12/20) form a connected cluster at 0.7 COMPARE correlation, with half of the non-connected mTOR singletons representative of the rapamycin class of inhibitors...NCI60 compound suppliers can incorporate their test compound(s) data to use the interactive visualization tools with AOD and IOA agents. This project was funded in part with federal funds from the NCI, NIH, under Contract # 75N91019D00024/75N91020F00003."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor • PIK3CA • PIK3CB

Immunogenic Death of Hepatocellular Carcinoma Cells in Mice Expressing Caspase-Resistant ROCK1 Is Not Replicated by ROCK Inhibitors. (PubMed, Cancers (Basel)) - "Both fasudil and AT13148 significantly decreased tumour numbers, areas and volumes, but neither resulted in greater numbers of neutrophils or CD8+ T cells to be recruited. These observations indicate that there is an important role for ROCK1 cleavage to limit immunogenic cell death, which was not replicated by systemic ROCK inhibitor administration. As a result, concomitant administration of ROCK inhibitors with cancer therapeutics would be unlikely to result in therapeutic benefit by inducing ICD to increase anti-tumour immune responses."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Oncology • Solid Tumor • CD8 • ROCK1

Small-Molecule Induction Promotes Corneal Endothelial Cell Differentiation From Human iPS Cells. (PubMed, Front Bioeng Biotechnol) - "The combination of A769662 and AT13148 upregulated the PKA/AKT signaling pathway, FOXO1 and PITX2 to promote the conversion of NCCs to CECs. We established an efficient small molecule-based method to differentiate hiPSCs into corneal endothelial-like cells, which might facilitate drug discovery and the development of cell-based therapies for corneal diseases."

Journal • Ophthalmology • AQP1 • TJP1 • VIM

First-in-human study of AT13148, a dual ROCK-AKT inhibitor in patients with solid tumors. (PubMed, Clin Cancer Res) - "AT13148 was the first dual potent ROCK-AKT inhibitor to be investigated for the treatment of solid tumors. The narrow therapeutic index and the pharmacokinetic profile led to recommend not developing this compound further. There are significant lessons learned in designing and testing agents that simultaneously inhibit multiple kinases including AGC kinases in cancer."

Clinical • Journal • P1 data • Dermatology • Fatigue • Hypotension • Oncology • Pneumonia • Solid Tumor

Phase I study of AT13148, a novel AGC kinase inhibitor (clinicaltrials.gov) - P1, N=40; Not yet recruiting; New P1 trial

New trial • Oncology

Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation. (PubMed, Metabolomics) - "AT13148 affects metabolites associated with NOS in cells, mice and patients which is consistent with the clinical dose-limiting hypotension."

Journal • Cardiovascular • Hypotension

Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarinoma Invasion and Tumor Growth. (PubMed, Cancer Res) - "These results suggest that AT13148 has anti-tumor properties that may be beneficial in combination therapies or in the adjuvant setting to reduce pancreatic cancer cell invasion and slow primary tumor growth. AT13148 might also have the additional benefit of enabling tumor resection by maintaining separation between tumor and healthy tissue boundaries."

Journal