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.
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- Formule: C104H189N49O22
- Masse moléculaire:2477.93
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:GMR-GAL4 driver, UAS-Tau2N4R, ElavC155-GAL4 driver, Oregon-R[3]
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Dosage:0.08 µM, 0.8 µM, 20 µM, 40 µM
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Administration:oral; continuous; lifespan or 6 weeks
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Result:Significantly improved eye size in GMR-hTau2N4R flies compared to untreated controls (40 µM).
Partially rescued the Tau-induced rough-eye phenotype, improving bristle number/morphology and reducing abnormal ommatidia; ommatidial disorganization was significantly reduced (20 µM).
Increased median survival of pan-neuronal hTau2N4R flies from 26 to 35 days (35% improvement; 0.8 µM).
Increased median survival of pan-neuronal hTau2N4R flies from 26 to 33 days (27% improvement; 0.08 µM).
Reduced total Tau aggregates (oligomers and fibrils) by 73% in pan-neuronal hTau2N4R flies; treated flies showed no fibrillar species, only large amorphous structures ~30-50 nm in diameter (0.08 µM).
Chemical Information
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Masse moléculaire 2477.93
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Formule C104H189N49O22
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Sequence
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
}-{D-Ile}-{d-Gln}-{d-Val}-Gly-{d-Arg}-NH2 -
Sequence Shortening
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
}-{D-Ile}-{d-Gln}-{d-Val}-G-{d-Arg}-NH2 -
Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[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. [Content Brief]
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RI-AG03 Related Classifications
HY-P10861 Related Classifications
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