Sustained FGFR Inhibition by PRN1371: A Promising Therapeutic Approach for Solid Tumors

A new drug, PRN1371, has been developed to target FGFRs, proteins linked to the growth of various cancers. This compound is a covalent and irreversible inhibitor, designed to bind tightly to the FGFR1, 2, 3, and 4 kinases, leading to a prolonged suppression of their activity. The drug is currently undergoing a phase 1 clinical trial for solid tumors.

The drug's effectiveness was evaluated using a microfluidics system to measure enzymatic activity and a cell proliferation assay to observe the impact over three days. Animal models with implanted tumors were also used to study the drug's pharmacodynamics and efficacy. When tumors reached a specific size, the mice were divided into groups and treated with PRN1371.

PRN1371 was found to be a potent and selective ATP competitor against the FGFR family, with IC50 values indicating its high potency. It showed no significant activity against other protein kinases, suggesting its selectivity. The drug was also found to be well-absorbed and had a dose and species-dependent bioavailability.

In animal models, PRN1371 significantly inhibited tumor growth and showed anti-tumor effects in various xenograft models with different FGFR pathway alterations. The phase 1 clinical trial is designed to assess the safety and tolerability of escalating doses of PRN1371 in patients with solid tumors.

In summary, PRN1371 is a promising candidate for treating cancers with FGFR alterations, and its clinical trial is currently in progress to evaluate its safety and effectiveness in humans.