OTS514 / OncoTherapy - LARVOL DELTA

PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites. (PubMed, Nat Commun) - "Eviction of Ikaros is rapidly reversed by addition of the PBK-inhibitor OTS514, revealing dynamic regulation by kinase and phosphatase activities...PBK-deficient cells were able to divide but showed altered chromatin accessibility and nucleosome positioning consistent with CTCF retention. Our studies reveal that PBK controls the dissociation of selected factors from condensing mitotic chromosomes and contributes to their compaction."

Journal • Hematological Malignancies • Oncology • IKZF1 • IKZF3

Targeting PBK in the fibroblast-to-myofibroblast transition: A novel therapeutic strategy for IPF. (PubMed, Biochem Pharmacol) - "Then, the bleomycin (BLM) -induced mouse model and human precision-cut lung slices (HPCLS) were utilized to detect the antifibrotic effects of the OTS514. Collectively, our data underscores the potential of OTS514 as an antifibrotic strategy by attenuating fibroblast-to-myofibroblast transition. Furthermore, the administration of OTS514 manifested no adverse effects in mouse model."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases

PBK expression promotes the aggressive phenotypes of mesothelioma (AACR 2025) - "We also found that a PBK inhibitor, OTS-514, suppressed the proliferation of these cell lines at low concentration...Multivariable Cox regression analysis, incorporating stage and OXTR mRNA expression, demonstrated that PBK mRNA expression was the strongest independent predictor of overall survival and the hazard ratio for PBK was higher than that for OXTR. Our findings indicate that PBK plays a crucial role in the aggressiveness of mesothelioma, making it a promising therapeutic target and potential prognostic biomarker for mesothelioma."

Mesothelioma • Oncology • Solid Tumor • AKT1 • PBK

The oncogenic kinase TOPK upregulates in psoriatic keratinocytes and contributes to psoriasis progression by regulating neutrophils infiltration. (PubMed, Cell Commun Signal) - "This study identified a crucial role of TOPK in psoriasis by regulating neutrophils infiltration, providing new insights into the pathogenesis of psoriasis."

Journal • Dermatitis • Dermatology • Immunology • Oncology • Psoriasis • CXCL1 • CXCL8 • IL17A • STAT3

Selective translational activation of PBK (PDZ- binding kinase) reveals a molecular vulnerability of drug-tolerant persister cells to targeted therapies in EGFR-mutant lung adenocarcinoma (AACR 2024) - "Consistently, combined treatment with osimertinib and OTS514 (PBK inhibitor) in vitro, reduces the DTPC fraction and decreases the enrichment of EMT-related transcriptional signatures. Finally, in matched diagnosis and relapse samples from 7 EGFR-mutant LUAD patients treated with EGFR inhibitors, we observed increased PBK activation at the time of acquired resistance in 5 cases, including 3 EGFRT790M-positive cases, suggesting that PBK activation may co-occur with genetic resistant alterations.Our findings unveil a novel mechanism by which EGFR-mutant lung cancer DTPCs selectively translate PBK mRNA as an adaptive survival mechanism to persist during osimertinib treatment; and provide a therapeutic target of non-genetic drug resistance otherwise unlooked-for in routine transcriptomic analyses. A deeper understanding on the mRNA translational reprogramming in DTPCs is currently performed to uncover therapeutic vulnerabilities to reduce residual disease and delay or revert..."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PBK • VIM • ZEB1

Topical application of TOPK inhibitor OTS514 suppresses psoriatic progression by inducing keratinocytes cell cycle arrest and apoptosis. (PubMed, Exp Dermatol) - "Mechanismly, inhibiting TOPK induces G2/M phase arrest and apoptosis of keratinocytes, thereby attenuating epidermal hyperplasia and disease progression. Collectively, this study identifies that upregulation of TOPK in keratinocytes promotes psoriatic progression, and inhibiting TOPK attenuates epidermal hyperplasia and psoriatic progression."

Journal • Dermatology • Immunology • Oncology • Psoriasis