The PI3K-AKT signaling pathway is frequently dysregulated across solid tumors, including PIK3CA-mutant cancers. While several PI3K and AKT inhibitors have been approved for clinical use, therapeutic benefit remains limited by feedback reactivation and incomplete pathway suppression. We developed a novel, orally active small-molecule degrader designed to achieve sustained AKT removal and pathway inhibition. Our AKT degrader lead molecule DWP221/PIN002 induced rapid and sustained degradation of AKT in tumor cells and demonstrated a strong correlation between systemic exposure and pharmacologic response after oral dosing in tumor-bearing mice. In vivo, the degrader achieved dose-dependent tumor growth inhibition and showed preferential distribution to tumor tissue. Exploratory combination with fulvestrant further improved tumor growth control, supporting potential therapeutic complementarity in hormone receptor-positive tumors. DWP221/PIN002 was well tolerated throughout the study period, without notable body-weight loss or overt signs of systemic toxicity, and maintained a favorable exposure-response relationship consistent with its drug-like properties. This study demonstrates that an orally bioavailable AKT degrader can achieve durable target suppression and in vivo efficacy through sustained exposure and efficient target engagement. These findings support that targeted protein degradation may overcome key limitations of conventional kinase inhibition and provide a differentiated approach toward next-generation targeted therapies for PI3K-AKT-driven cancers.