HMN-214 / Nippon Shinyaku - LARVOL DELTA

Polo-like kinase inhibitors increase AAV production by halting cell cycle progression. (PubMed, Mol Ther Methods Clin Dev) - "Inhibiting PLK1 with HMN-214 increased AAV production, which was largely consistent across HEK293 cell lines, vector payloads, and capsid serotypes. Using cell cycle and RNA-sequencing analysis, we showed that PLK1 inhibition halts cells in the G2/M phase and blocks their exit from the M to G1 phase. These findings support that inhibiting PLK1 may enhance AAV production and could be used to develop more cost-effective methods to manufacture AAV for gene therapies."

Journal • Gene Therapies

Inhibition of Polo-Like Kinase 1 Dampens the Replication of Vaccinia Virus in Mammalian Cells. (PubMed, J Med Virol) - "This study confirms the effects of the PLK1 inhibitors HMN-214 and ON-01910 on VACV replication in A549 cells. However, despite its strong in vitro effects, ON-01910 did not significantly reduce VACV replication in mice. These findings highlight the critical role of PLK1 in VACV replication and its potential as a target for antiviral therapy against orthopoxviruses."

Journal • Dermatology • Infectious Disease • PLK1

Identification of Inhibitors of Tubulin Polymerization Using a CRISPR-Edited Cell Line with Endogenous Fluorescent Tagging of β-Tubulin and Histone H1. (PubMed, Biomolecules) - "The cells were treated with known tubulin polymerization inhibitors, colchicine, and vincristine, and the resulting phenotypic changes indicative of tubulin polymerization inhibition were confirmed using HCI. Furthermore, a library of 429 kinase inhibitors was screened, resulting in the identification of three compounds (ON-01910, HMN-214, and KX2-391) that inhibit tubulin polymerization. Live cell tracking analysis confirmed that compound treatment leads to rapid tubulin depolymerization. These findings suggest that CRISPR-edited cells with fluorescently tagged endogenous β-tubulin can be utilized to screen large compound libraries containing diverse chemical families for the identification of novel tubulin polymerization inhibitors."

Journal • Preclinical • Oncology

Inhibition of Polo-like Kinase 1 by HMN-214 Blocks Cell Cycle Progression and Inhibits Neuroblastoma Growth. (PubMed, Pharmaceuticals (Basel)) - "HMN-214 is a prodrug of HMN-176 and is known to selectively interfere with PLK1 function. In the NB 3D spheroid tumor model, HMN-214 significantly and in a dose-dependent manner inhibits spheroid tumor mass and growth. Overall, our study highlights that targeting PLK1 using HMN-214 is a novel therapeutic approach for NB."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • CCNB1 • CDK1 • CDK2 • CHEK1 • CHEK2 • MYCN • PLK1

Inhibition of PLK-1 by using a Small Molecule Inhibitor HMN-214 is a Novel Therapeutic Approach for High-risk Neuroblastoma. (PubMed, FASEB J) - "Overall, our data highlights the role of PLK-1 in the oncogenic progression of NB and showed the efficacy of HMN-214 in inhibiting NB growth. Our future efforts will be directed towards elucidating the role of PLK-1 in NB and developing effective therapeutic strategies incorporating PLK-1 inhibitor."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • CDK1 • MYCN • PLK1