PROTACFAKdegrader 2 (Compound F2) is a PROTAC degrader targeting focal adhesion kinase (FAK), with DC50 values for total FAK and phosphorylated p-FAK of 27.72 nM and 60.1 nM, respectively. It inhibits the viability of cancer cell lines 4T1, MDA-MB-231, MDA-MB-468, and MDA-MB-435, with IC50 values ranging from 0.73 to 5.84 μM. Additionally, PROTACFAKdegrader 2 counteracts multidrug resistance (MDR) by inhibiting the AKT and ERK signaling pathways. In HCT/8 xenograft mouse models, it demonstrates anti-tumor efficacy.