GBO-006-1 / Traws Pharma - LARVOL DELTA

Discovery of novel pyrazolo[3,4-d]pyrimidine-6-amine derivatives as potent polo-like kinase 2 inhibitors. (PubMed, Eur J Med Chem) - "Notably, compound 11 showed significant in vivo tumor growth efficacy in a xenograft mouse model (TGI = 69.37%), markedly superior to ON1231320 (TGI = 8.36%) with favorable pharmacokinetic parameters. These findings establish pyrazolo[3,4-d]pyrimidine derivatives as promising PLK2 inhibitors with strong therapeutic potential for colorectal cancer."

Journal • Colorectal Cancer • Oncology • Solid Tumor • PLK2

Integrative analysis of polo-like kinase family identifies a prognostic signature and validates PLK2 as a therapeutic target in glioma. (PubMed, Transl Cancer Res) - "Our study highlights the prognostic value of the PLK gene family in glioma and identifies PLK2 as a promising therapeutic target. The PLK2 inhibitor ON1231320 shows potential as an anti-GBM agent and warrants further investigation in preclinical and clinical studies."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • PLK1 • PLK2

Genome-wide CRISPR Screening in Embryonic Stem Cells Identifies Synthetic Lethality Interactions in MLH1 and TP53 Deficient Tumors (EACR 2025) - "We further validated the effects of SR1848 (which inhibits NR5A2), ON1231320 or BI2536 (which inhibit PLK2), and blebbistatin (which inhibits MYH10) in cancer cell lines with and without LoF mutations in MLH1 or TP53. Overall, our findings show the potential of genetic screening in haploid hESCs in identifying selective inhibitors and therefore advancing the realm of cancer precision medicine."

Synthetic lethality • Oncology • Solid Tumor • MLH1 • NR5A2 • PLK2 • TP53

Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours. (PubMed, Cell Prolif) - "The specific effects of SR1848, which inhibits NR5A2, ON1231320 or BI2536, which inhibits PLK2, and blebbistatin, which inhibits MYH10, were further validated in cancer cell lines. Finally, animal studies with CCL xenografts showed the selective effect of the small molecule BI2536 on MLH1-null tumours and of blebbistatin on TP53-mutated tumours. Thus, demonstrating their potential for personalised medicine, and the robustness of genetic screening in haploid hESCs in the context of cancer therapeutics."

Biomarker • Journal • Oncology • MLH1 • NR5A2 • PLK2 • TP53

Polo-like kinases as potential targets and PLK2 as a novel biomarker for the prognosis of human glioblastoma. (PubMed, Aging (Albany NY)) - "In glioma cells, ON1231320 has anticancer effects. Finally, a summary of PLK inhibitors is presented, along with projections for future progress."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • PLK1 • PLK2