TAK-960 / Takeda - LARVOL DELTA

All Screens Lead to Polo-like kinase 1: A Central Node in Cancer Therapeutics and Resistance. (PubMed, Pharmacol Res) - "Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo- and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment."

Journal • Review • Oncology • PLK1

Selective Inhibition of Protein Kinase D2 Activity Reduces Human Neutrophil Survival. (PubMed, Anticancer Res) - "PKD2 plays a crucial role in human neutrophil survival. Minimizing PKD2 inhibition during small-molecule drug design could be essential to reduce the risk of neutropenia in patients under anti-cancer treatment."

Journal • Colon Cancer • Colorectal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • PKD2

INTEGRATING PATIENT-DERIVED MODELS AND MULTI-OMIC PROFILING: A PRECISION MEDICINE PLATFORM FOR NEUROBLASTOMA DRUG DISCOVERY (SIOP 2025) - "Conclusions We establish NB patient-derived cell, organoid, xenograft and multi-omics-based platform for personalized therapy of NB. In a brain metastasis NB, CGP60474, SB1317 and TAK-960 were identified to have anti-NB effect and validated in a NB cell line."

Clinical • Neuroblastoma • Solid Tumor • CHGA • HOXB6 • PHOX2B

Polo-like kinase 1 inhibition modulates urinary tract smooth muscle contraction and bladder cell transcriptional programs. (PubMed, Cytoskeleton (Hoboken)) - "This work reveals PLK1 reduction with the selective inhibitor TAK-960 (500 nM) suppresses high K+-evoked contractions of human urinary smooth muscle ex vivo while decreasing urothelial cell viability...Targeting PLK1 pharmacologically may therefore offer therapeutic potential to ameliorate hypercontractility and aberrant growth. Further elucidation of PLK1 signaling networks promises new insights into pathogenesis and much needed treatment advances for debilitating urinary symptoms."

Journal • Overactive Bladder • PLK1

Influence of pole-like kinase 1 on controlling contractility of the urinary tract and gene activated patterns of human bladder smooth muscle cells. (PubMed, FASEB J) - "Our findings point to a certain role of PLK-1 in of proliferation in hBSMCs and contractility in ureterovesical junction smooth muscle, which may be of relevance in lower urinary tract symptom. PLK-1 inhibitors block these effects and show shared and divergent effects. PLK-1 regulation of bladder smooth muscle growth and contraction may include genomic and nongenomic mechanisms."

Journal • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Oncology • Systemic Lupus Erythematosus • Transplantation • CCL11 • KRT18 • MEN1 • PLK1 • TNFSF10

Phase 1 dose escalation study of the investigational drug TAK-960, an oral polo-like kinase 1 (PLK1) inhibitor, in patients (pts) with advanced solid tumors (ESMO-ECCO-ESTRO 2013) - Presentation time: 29 September 2013, 09:30 - 12:00; Abstract# 868; P1, N=32; Sponsor: Millennium Pharmaceuticals; NCT01179399; “The study was terminated due to business reasons before the MTD or RP2D were established, a further 21-d cycle was considered (7-d QD then 14-d rest period). In 31 PK evaluable pts, TAK-960 was characterized by a median Tmax of 6hr, low fluctuation at steady-state (overall mean peak-to-trough ratio of 1.4), and moderately long mean t1/2 of 48hr.”

P1 data • Oncology