XL-784 is a selective inhibitor of matrix metalloproteinases (MMPs) with IC50 values of approximately 1900, 0.81, 120, 10.8, 18, and 0.56 nM for MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, respectively. XL-784 demonstrates potential in a broad range of cancer research applications due to its capability to modulate extracellular matrix remodeling, tumor invasion, and metastasis.

MMP1:1900 nM, MMP2:0.81 nM, MMP13:0.56 nM, MMP3:120 nM, MMP9:18 nM, MMP8:10.8 nM

XL-784 exhibits inhibitory activity against multiple targets in vitro, with particularly pronounced effects on MMP-2, MMP-13, and ADAM10 (also known as TNF-α converting enzyme, TACE), demonstrating IC50 values concentrated within the 1-2 nM range [1].
XL-784 also shows inhibitory effects on MMP-9 and ADAM17, with corresponding IC50 values of approximately 20 nM and 70 nM, respectively [1].
The compound exhibits weaker inhibitory activity against MMP-1, with an IC50 value of approximately 2000 nM [1].

XL-784 significantly inhibited the expansion of abdominal aortic aneurysm in mice at all tested doses. The XL784 dose groups of 50 mg/kg, 125 mg/kg, and 250 mg/kg resulted in maximum aneurysm expansion percentages of 140.4%±3.2%, 129.3%±5.1%, and 119.2%±3.5%, respectively, all of which were significantly lower than the control group. Furthermore, higher doses of XL784 (375 mg/kg and 500 mg/kg) exhibited even more pronounced inhibitory effects on aneurysm expansion, with maximum expansion percentages of 88.6%±4.4% and 76.0%±3.5%, respectively, both significantly lower than the control group. This indicates a clear dose-response relationship for XL784 [2].