INCB3619 is a selective and orally active ADAM inhibitor with IC50 of 22 nM and 14 nM for ADAM10 and ADAM17, respectively. INCB3619 has anti-tumor activity.
INCB3619 (0-10 μM, 96 h) can inhibit heregulin-dependent HER3-Akt pathway, but not ERK activity in A549 cells, and induce apoptosis in A549 cells[1]. INCB3619 (0-10 μM, 72 h) can inhibit EGFR ligand signaling in the EGFR autocrine cell line NCI-H1666 and can be used in combination with other anti-EGFR drugs such as gefitinib[1].INCB3619 (2 µM) inhibits ERK1/2 expression in NCI-H1666 and make it sensitive to Gefitinib [1].
INCB3619 (subcutaneous injection, 60 mg/kg/d, 14 d) exhibits antitumor activity and sensitizes tumors to Gefitinib in A549 xenografted BALB/c nu/nu mouse model[1].
References:
[1]. Bin-Bing S Zhou, et al. Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell. 2006 Jul;10(1):39-50.