Discovery and optimization of a guanylhydrazone-based small molecule to replace bFGF for cell culture applications.

ABSTRACT: Replacing growth factors with a synthetic alternative molecule is an attractive opportunity to increase consistency, scalability, and cost-effectiveness of cell-based products. Herein, we describe the discovery of a chemical class of FGFR1 agonists that mimic the action of basic fibroblast growth factor (bFGF), an essential component of cell culture media. The guanylhydrazone-based molecule, TCB-32, was identified via structure-based virtual screening of the orthosteric binding site of FGFR1. It was shown to significantly increase cell proliferation by activating the FGFR1 signaling pathway like bFGF and exhibited enhanced thermostability over bFGF by retaining activity over the course of several days. After extensive structure-activity relationship studies, it was possible to increase pot

SUBMITTER: Feofanov M 

PROVIDER: S-EPMC12305320 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature