Discovery of Futibatinib: The First Covalent FGFR Kinase Inhibitor in Clinical Use.

Deregulating fibroblast growth factor receptor (FGFR) signaling is a promising strategy for cancer therapy. Herein, we report the discovery of compound (TAS-120, futibatinib), a potent and selective covalent inhibitor of FGFR1-4, starting from a unique dual inhibitor of mutant epidermal growth factor receptor and FGFR (compound ). Compound inhibited all four families of FGFRs in the single-digit nanomolar range and showed high selectivity for over 387 kinases.

Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors.

FGFR signaling is deregulated in many human cancers, and FGFR is considered a valid target in FGFR-deregulated tumors. Here, we examine the preclinical profile of futibatinib (TAS-120; 1-[(3S)-[4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3, 4-d] pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one), a structurally novel, irreversible FGFR1-4 inhibitor. Among a panel of 296 human kinases, futibatinib selectively inhibited FGFR1-4 with IC values of 1.

A Clinical Association between an Increasing Renal Resistive Index and the Atherosclerotic Burden in Patients with a Preserved Renal Function.

Objective A positive correlation is observed between the progression of renal impairment and the increasing risk of cardiovascular disease. Our aim was to examine the relationship between the renal resistive index (RRI) assessed by duplex sonography and the extent of atherosclerosis in patients without renal impairment undergoing vascular imaging studies. Methods The RRI was evaluated pre-procedurally among 106 outpatients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.

Protective activity of anti-lipoteichoic acid monoclonal antibody in single or combination therapies in methicillin-resistant Staphylococcus aureus-induced murine sepsis models.

Previously, we generated and screened a panel of monoclonal antibodies (mAbs) against methicillin-resistant Staphylococcus aureus (MRSA) to identify protective mAbs in mouse infection models. One of these mAbs, ZBIA3H, bound to lipoteichoic acid (LTA) and exerted protective effects in a mouse sepsis model. To reinforce the ability of the mAb to protect against infection, combination therapies with the mAb and antibiotics need to be examined.