| In Vitro |
UNC-CA359 (compound 45) loses activity on U-CH1, leaves some activity on U-CH2, and maintains inhibition on EGFR, with IC50s of >100 μM, 35 μM, and 18 nM, respectively[1]. UNC-CA359 (1 nM-0.1 mM; 72 h) has activity against chordoma with IC50s of 1.2 μM (CH22), and 3.0 μM (U-CH12), respectively[1]. UNC-CA359 shows UNC-CA359 (compound 102) has three main collateral kinase targets, and shows high potency towards SLK/STK10 with a promising selectivity ratio (NAK over SLK/STK10) of 22, while the binding constant Ki values are 3.4 nM (GAK), 0.33 μM (SLK), 0.075 μM (STK10), respectively[2]. GAK: cyclin G associated kinase; SLK: STE20-like serine/threonine-protein kinase; STK10: serine/threonine-protein kinase 10. Cell Cytotoxicity Assay[1] Cell Line: Chordoma cell lines: CH22, UM-Chor1, U-CH12 and U-CH7; WS1 Concentration: 1 nM-100 μM Incubation Time: 72 hours Result: Demonstrated good potential against chordoma cells, with IC50s of 1.2 μM (CH22), 3.0 μM (U-CH12), 60 μM (UM-Chor1), 74 μM (U-CH7), respectively. Showed no toxicity towards WS1 cell (IC50 >100 μM).
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