| Identification | Back Directory | [Name]
AG-10 1446711-81-4 | [CAS]
1446711-81-4 | [Synonyms]
Acoramidis
AG-10 1446711-81-4
3-(3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid
Benzoic acid, 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluoro- | [Molecular Formula]
C15H17FN2O3 | [MOL File]
1446711-81-4.mol | [Molecular Weight]
292.31 |
| Chemical Properties | Back Directory | [Boiling point ]
542.5±50.0 °C(Predicted) | [density ]
1.282±0.06 g/cm3(Predicted) | [solubility ]
DMSO: Soluble: =10 mg/ml
Ethanol: Slightly soluble: 0.1-1 mg/ml | [form ]
Solid | [pka]
3.98±0.10(Predicted) | [color ]
White to off-white | [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]
C(O)(=O)C1=CC=C(F)C(OCCCC2=C(C)NN=C2C)=C1 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
| Animal Model: | Wistar rats[1]. | | Dosage: | 50 mg/kg/d (Toxicity Analysis). | | Administration: | Oral gavage, daily for 28 d. | | Result: | Showed the plasma Cmax of ～40 μM and histopathological evaluation of liver, kidney, heart, spleen, thymus, and lung showed no signs of pathologic processes in the AG10-treated animals |
| [References]
[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. DOI:10.1073/pnas.1300761110
[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. DOI:10.1002/cpdd.700
[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. DOI:10.1074/jbc.M305396200 |
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