KVX-053 / KeViRx - LARVOL DELTA

The PTP4A3 inhibitor KVX-053 reduces Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virulence, inflammation, and development of acute lung injury in K18-hACE2 mice. (PubMed, Respir Res) - "KVX-053, a potent and selective PTP4A3 inhibitor, emerges as a promising host-directed therapeutic strategy for mitigating ARDS and inflammation-driven lung injury in SARS-CoV-2 and potentially other respiratory viral infections. Future studies are required to optimize dosing strategies, elucidate precise molecular mechanisms, and validate these findings in clinical settings."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CXCL10 • CXCL11 • IL6 • NLRP3 • PTP4A3 • TNFA

Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs. (PubMed, Mol Oncol) - "Gene silencing of PTP4A3 resulted in the upregulation of compensatory mechanisms that overcame the loss of PTP4A3 expression, but this was mitigated by pan-PTP4A inhibition with JMS-053 in HGSOC cells. Moreover, shRNA-mediated silencing of PTP4A3 sensitised HGSOC cells to clinically relevant chemotherapeutic drugs. Overall, we show that compensatory mechanisms from PTP4A1 and PTP4A2 can arise when specifically targeting PTP4A3 in HGSOC and that pan-PTP4A inhibition can overcome those effects."

Journal • Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • PTP4A3

Intravenous Administration of KVX-053, A PTP4A3 Inhibitor, Prevents Ventilator-induced Lung Injury (VILI) in Mice (ATS 2025) - " C57Bl/6j mice were anesthetized with Ketamine/xylazine (90 mg and 9 mg/kg), their trachea was isolated and connected to a Flexivent small animal ventilator (SCIREQ). Our data suggest that KVX-053 may strengthen the alveolar barrier function and mitigate the severity of VILI. Our results could expand the translational potential of PTP4A3 inhibition in Emergency Medicine, by providing safe and beneficial effects in patients undergoing mechanical ventilation."

Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Anesthesia • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • PTP4A3

Protective Effects of KVX-053, A PTP4A3 Inhibitor, on Pulmonary Vascular Endothelial Damage Induced by Alcohol and Metabolites (ATS 2025) - "Our findings suggest AA could be a key factor in vascular endothelial damage among individuals with alcohol abuse. The PTP4A3 inhibitor KVX-053 has the potential to reduce this damage and minimize the risk of alcohol-induced pulmonary pathologies, such as acute respiratory distress syndrome and pulmonary hypertension."

Acute Respiratory Distress Syndrome • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CDH5 • PTP4A3

KVX-053, a protein tyrosine phosphatase 4A3 inhibitor, ameliorates SARS-CoV-2 spike protein subunit 1-induced acute lung injury in mice. (PubMed, J Pharmacol Exp Ther) - "Intratracheal administration of SARS-CoV-2 spike protein subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines and chemokines, structural lung injury, and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings suggest that this novel PTP4A3 inhibitor may be useful against COVID-19 and potentially other viral-induced ARDS."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • ACE2 • PTP4A3

KVX-053, a Protein Tyrosine Phosphatase 4A3 inhibitor, ameliorates SARS-CoV-2 Spike protein subunit 1 - induced acute lung injury in mice. (PubMed, J Pharmacol Exp Ther) - "Intratracheal administration of SARS-CoV-2 Spike protein Subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines and chemokines, structural lung injury and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings suggest that this novel PTP4A3 inhibitor may be useful against COVID-19 and potentially other viral-induced ARDS."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • ACE2 • PTP4A3

PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization Under Microenvironmental Pressure. (PubMed, Cancer Res Commun) - "Here we report that pharmacological treatment using JMS-053, a pan-PRL inhibitor, inhibits GB cell viability and spheroids growth...In vitro assays show that cell proliferation is not affected in PTP4A2 deficient or overexpressing cells highlighting the importance of the microenvironment in PTP4A2 functions. Collectively, our results indicate that PTP4A2 promotes GB growth in response to microenvironmental pressure and supports the targeting of PTP4A2 as therapeutic strategy against GB."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

PTP4A3 Inhibitors Ameliorate SARS-CoV-2-related ARDS by Stimulating Alcohol Metabolism (ATS 2024) - "We conclude that the severity of ethanol-exacerbated, SARS-CoV-2-induced ARDS is ALDH-dependent, and that PTP4A3 inhibitors ameliorate- at least in part- SARS-CoV-2-related ARDS, exacerbated by alcohol consumption, by stimulating ALDH phosphorylation and activation."

Acute Lung Injury • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • NLRP3 • PTP4A3

Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma: A multi-computational investigation. (PubMed, Comput Biol Chem) - "Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands...Escitalopram oxalate exhibited a comparatively significant docking score (-7.4 kcal/mol) compared to the control JMS-053 (-6.8 kcal/mol) against the PRL-3 protein...The docked complexes were subjected to MD studies (100 ns) showing stable interactions. Considering all the findings, it can be concluded that Escitalopram oxalate and related therapeutics can act as potential pharmacological candidates for targeting the activity of PTP4A3/PRL-3 in HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • PTP4A3

KVX-053, A PTP4A3 INHIBITOR, MODULATES THE ENDOCYTIC PATHWAY, EXTRACELLULAR VESICLE UPTAKE, ENDOTHELIAL BARRIER DYSFUNCTION AND THE DEVELOPMENT OF ARDS IN VITRO AND IN VIVO (CHEST 2023) - "Our preliminary data suggest that KVX-053 inhibits the uptake of circulating EVs, their harmful effects on lung endothelial barrier function, and the development of ARDS in mice. CLINICAL IMPLICATIONS: KVX-053 represents a promising, novel therapeutic approach for mitigating pulmonary inflammation in ARDS. Further study in this area is warranted."

Preclinical • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • PTP4A3

The PTP4A3 Inhibitor, KVX-053, Ameliorates Alcohol-exacerbated SARS-CoV-2-induced ARDS (ATS 2023) - "We conclude that the PTP4A3 inhibitor KVX-053 ameliorates SARS-CoV2-related ARDS, exacerbated by alcohol consumption."

Late-breaking abstract • Acute Lung Injury • Acute Respiratory Distress Syndrome • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • ACE2 • NF-κβ • NLRP3 • PTP4A3

Disruption of ovarian cancer STAT3 and p38 signaling with a small molecule inhibitor of PTP4A3 phosphatase. (PubMed, J Pharmacol Exp Ther) - "We generated A2780 and OVCAR4 ovarian cancer cells resistant to JMS-053 and the resulting cells were not cross-resistant to paclitaxel, cisplatin or teniposide. Significance Statement We demonstrate that chemical inhibition of PTP4A phosphatase activity with JMS-053 decreases STAT3 activation and increases SHP-2 phosphatase and p38 kinase phosphorylation activation in ovarian cancer cells. The newly developed JMS-053 resistant ovarian cancer cells should provide useful tools to further probe the role of PTP4A phosphatase in ovarian cancer cell survival and cell signaling."

Journal • Oncology • Ovarian Cancer • Solid Tumor • PTP4A3