INCB3619

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[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

INCB3619 (0-0.25 μM, 96 h) 可以抑制 heregulin 依赖性 HER3-Akt 通路，但不能抑制 A549 细胞中的 ERK 活性，可诱导 A549 细胞凋亡[1]。 INCB3619 (0-10 μM, 72 h) 可以抑制 EGFR 自分泌细胞系 NCI-H1666 中的 EGFR 配体信号传导，并可与其他抗 EGFR 药物，如吉非替尼联合使用[1]。 INCB3619 (2 µM) 抑制 NCI-H166 细胞中 ERK1/2 的表达，使其对吉非替尼 (Gefitinib，HY-50895) 敏感[1]。 Apoptosis Analysis[1]. Cell Line: A549 cell Concentration: 1, 10 μM Incubation Time: Result: Induced about 3% apoptosis at a concentration of 1 μM and about 5% at a concentration of 10 μM. Cell Viability Assay[1]. Cell Line: NCI-H1666 cell Concentration: 0-10 μM Incubation Time: 72 h Result: Inhibited proliferation of NCI-H1666 cells.

INCB3619 (subcutaneous injection，60 mg/kg/d，14 d) 在 A549 异种移植的 BALB/c nu/nu 小鼠模型中，具有抗肿瘤活性，并使肿瘤对吉非替尼 (Gefitinib，HY-50895) 敏感[1]。 Animal Model: BALB/c nu/nu mouse model of A549 xenograft Dosage: 50, 60 mg/kg Administration: subcutaneous injection, daily, 14 d Result: Significant tumor growth inhibition and delay at 60 mg/kg dose, less active effect at 50 mg/kg.

[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.