UNC-CA359 is a highly potent inhibitor of the epidermal growth factor receptor (EGFR), demonstrating an IC50 value of 18 nM. With strong anti-tumor activity, UNC-CA359 holds significant potential for chordoma research [1].

UNC-CA359, also referred to as compound 45, demonstrates varying levels of activity across different targets: it is ineffective against U-CH1, partially effective on U-CH2, and strongly inhibits EGFR with IC50 values of >100 μM, 35 μM, and 18 nM, respectively. When tested in chordoma cell lines for 72 hours at concentrations ranging from 1 nM to 0.1 mM, UNC-CA359 exhibits IC50 values of 1.2 μM in CH22 and 3.0 μM in U-CH12 cells. Furthermore, it targets three collateral kinases, showing notable potency towards SLK/STK10 with a selectivity ratio over NAK of 22. The binding constants (Ki) for GAK, SLK, and STK10 are 3.4 nM, 0.33 μM, and 0.075 μM, respectively. In a cytotoxicity assay involving various chordoma cell lines and WS1 cells, it showed promising activity against the chordoma cells with IC50 values of 1.2 μM (CH22), 3.0 μM (U-CH12), 60 μM (UM-Chor1), and 74 μM (U-CH7), while exhibiting no toxicity toward WS1 cells (IC50 >100 μM).