Tucatinib (Irbinitinib) hemiethanolate is a potent, orally active, and selective HER2 inhibitor with an IC50 of 8 nM.

HER2:8 nM (IC50)

Tucatinib hemiglycolate has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 over EGFR in cell-based assays. Tucatinib selectively inhibits the receptor tyrosine kinase HER2 but not EGFR[1].

Tucatinib hemiethanolate (ONT-380 hemiethanolate, 200 mg/kg/d) improves survival at maximum-tolerated dose[1] and reduces brain pErbB2 levels by 80%[2]. This compound (ARRY-380 hemiethanolate) shows significant tumor growth inhibition (TGI)—50% at 50 mg/kg/d and up to 96% at 100 mg/kg/d, with over 50% reduction in baseline tumor size in 9 out of 12 animals at the higher dosage. When combined with trastuzumab at 50 mg/kg/d, it achieves 98% TGI, with complete regressions in 9 out of 12 animals and partial regressions in two[3].