RI-AG03 

RI-AG03 is a proteolytically stable tau aggregation inhibitor that crosses the blood-brain barrier and exhibits oral efficacy. RI-AG03 inhibits tau aggregation and promotes the formation of alternative amorphous aggregates that are non-amyloidogenic. RI-AG03 mediates cellular uptake through direct membrane penetration and macropinocytosis, and its conjugation with cell-penetrating peptide sequences (CPPs) enhances the binding of cells to liposomes. RI-AG03 suppresses aggregation-dependent neurodegenerative and behavioral phenotypes, and extends the lifespan of Drosophila models of tauopathy. RI-AG03 can be used for research on tau-related diseases such as Alzheimer's disease^[1][2][3].

Liposomes conjugated with RI-AG03 (75 μM; 4 h) show significantly enhanced binding to SH-SY5Y cells^[2].
RI-AG03 (20 µM; 24 h) potently inhibits the aggregation of recombinant 306VQIVYK311, 275VQIINK280, and the mixed 306VQIVYK311 + 275VQIINK280 hexapeptides^[3].
RI-AG03 (0.5-200 µM; 24 h) dose-dependently inhibits heparin-induced aggregation of recombinant TauΔ1-250, with an IC₅₀ of 7.83 µM^[3].
RI-AG03 (0.5-200 µM; 216 h) inhibits heparin-induced aggregation of recombinant full-length Tau2N4R in a dose-dependent manner, with an IC₅₀ of 5 µM^[3].
RI-AG03 (20 µM; 24 h) inhibits the formation of recombinant TauΔ1-250 fibrils and instead promotes the formation of large spherical amorphous aggregates^[3].
RI-AG03 (20 µM; 5 h) reduces the conversion of recombinant TauΔ1-250 from a disordered random coil structure to β-sheet-rich aggregates^[3].
RI-AG03 (0.5-500 µM; 16 h preincubation, 24 h cell incubation) dose-dependently inhibits the seeding aggregation of preformed Tau2N4R fibrils in HEK-293 Tau biosensor cells, with an IC₅₀ of 23.85 µM, and shows no toxicity at effective doses up to 100 µM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

RI-AG03 (0.08-40 µM; p.o.; continuous dosing; throughout the lifespan or for 6 weeks) reduces Tau aggregation in Drosophila melanogaster, rescues aggregation-dependent neurodegenerative eye phenotypes, and increases the median survival rate of flies expressing hTau2N4R by up to 35% at the dose of 0.8 µM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

2477.93

C₁₀₄H₁₈₉N₄₉O₂₂

Ac-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-Gly-{d-Pro}-{d-Lys}-{d-Tyr}-{d-Lys<Ac>}-{D-Ile}-{d-Gln}-{d-Val}-Gly-{d-Arg}-NH2

Ac-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-{d-Arg}-G-{d-Pro}-{d-Lys}-{d-Tyr}-{d-Lys<Ac>}-{D-Ile}-{d-Gln}-{d-Val}-G-{d-Arg}-NH2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Di Natale G, et al. Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer's Disease?. Molecules. 2022;27(16):5066. Published 2022 Aug 9.  [Content Brief]

  [2]. Reich N, et al. Liposome nanoparticle conjugation and cell penetrating peptide sequences (CPPs) enhance the cellular delivery of the tau aggregation inhibitor RI-AG03. J Cell Mol Med. 2024;28(11):e18477.

  [3]. Aggidis A, et al. A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies. Alzheimers Dement. 2024;20(11):7788-7804.  [Content Brief]