SJ-300 is a selective, orally active DKK3-LRP1 inhibitor capable of crossing the blood-brain barrier. It binds to mLRPIV with a Kd of 7.9 μM and inhibits the DKK3-mLRPIV complex with an IC50 of 3.2 μM, without affecting the interaction between Aβ and LRP1. In Alzheimer's disease models, SJ-300 restores Aβ clearance functionality, improves cognitive function, and reduces neuropathology by approximately 73.3% (Aβ plaque reduction). SJ-300 is suitable for research related to Alzheimer's disease.

SJ-300 significantly reduces the interaction between DKK3 and mLRPIV in SH-SY5Y cells at concentrations ranging from 0 to 5 μM. It restores the internalization of Aβ in AD-NSC cells at 1 μM for 2 hours. At 10 μM, SJ-300 does not directly affect the canonical Wnt/β-catenin signaling pathway in SH-SY5Y cells. SJ-300 demonstrates excellent metabolic stability in mouse and human liver microsomes at 50 μM (in 2 μL) over 0 to 60 minutes.

In the study involving C57 mice, SJ-300 (single intravenous injection at 2 mg/kg or single oral dose at 10 mg/kg) maintained a consistent plasma concentration throughout the observation period. When administered as a single oral gavage (10 mg/kg), SJ-300 demonstrated remarkable ability to penetrate the brain, with a brain/plasma concentration ratio (B/P ratio) reaching 5732%. SJ-300 administered orally at 10 mg/kg showed exceptional blood-brain barrier penetration capabilities in C57 mice, with a brain/plasma ratio as high as 5732%. In a different study with 5×FAD transgenic Alzheimer's disease model mice, SJ-300 (oral, 5 mg/kg, once daily for 8 weeks) improved cognitive function with minimal correlation to Aβ pathology. Additionally, SJ-300 (oral, 5 mg/kg, once daily for 8 weeks) alleviated cognitive deficits and AD pathology in 6-month-old 5×FAD mice through enhanced Aβ clearance.