For research use only. Not for therapeutic Use.
Acoramidis (AG10) is an orally active and selective kinetic stabilizer of WT and V122I-TTR (transthyretin). Acoramidis (AG10) is used in the study for transthyretin amyloidosis[1][2].
Acoramidis (AG10, 0.1-10 μM for TTR ∼5 µM) stabilizes V122I- and WT-TTR equally well and also exceeds their efficacy to stabilize WT and mutant TTR in whole serum[1].
Acoramidis (AG10) stimulates the mitochondrial QO2 in a concentration-dependent manner between 10 and 100 μM[3].
Acoramidis (AG10) has very minimal inhibition of two common off-targets in drug discovery, the potassium ion channel hERG (IC50 > 100 µM) and a number of cytochrome P450 isozymes (IC50 > 50 µM) (low toxicity)[1].
| Catalog Number | I021492 |
| CAS Number | 1446711-81-4 |
| Synonyms | 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid |
| Molecular Formula | C15H17FN2O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C15H17FN2O3/c1-9-12(10(2)18-17-9)4-3-7-21-14-8-11(15(19)20)5-6-13(14)16/h5-6,8H,3-4,7H2,1-2H3,(H,17,18)(H,19,20) |
| InChIKey | WBFUHHBPNXWNCC-UHFFFAOYSA-N |
| SMILES | CC1=C(C(=NN1)C)CCCOC2=C(C=CC(=C2)C(=O)O)F |
| Reference | [1]. Sravan C Penchala, et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9992-7. [2]. Jonathan C Fox, et al. First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2020 Jan;9(1):115-129. [3]. Stephen P Soltoff, et al. Evidence that tyrphostins AG10 and AG18 are mitochondrial uncouplers that alter phosphorylation-dependent cell signaling. J Biol Chem. 2004 Mar 19;279(12):10910-8. |
