[CAS NO. 2242751-53-5] Acoramidis hydrochloride
PRODUCTS SPECIFICATIONS [2242751-53-5]
DESCRIPTION [2242751-53-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 328.77 |
| Molecular Formula | C15H18ClFN2O3 |
| SMILES | O=C(O)C1=CC=C(F)C(OCCCC2=C(C)NN=C2C)=C1.[H]Cl |
Summary
Acoramidis (AG10) hydrochloride is an orally active and selective kinetic stabilizer of WT and V122I- TTR (transthyretin) . Acoramidis (AG10) hydrochloride is used in the study for transthyretin amyloidosis [1] [2] .
In Vitro
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 (IC
50
> 100 µM) and a number of cytochrome P450 isozymes (IC
50
> 50 µM) (low toxicity)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1] .
| Cell Line: | Human serum (TTR ∼5 µM). |
| Concentration: | 0.1 and 10 μM. |
| Incubation Time: | 72 h. |
| Result: |
Was significantly more effective than tafamidis in stabilizing TTR.
The concentration of AG10 to 10 µM resulted in stabilization of almost all of TTR in serum. |
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 C max 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 |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04769479 | Eidos Therapeutics, a BridgeBio company |
Amyloidosis
|
March 28, 2021 | Phase 1 |
| NCT04882735 | Eidos Therapeutics, a BridgeBio company |
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
|
September 2021 | Phase 3 |
| NCT03860935 | Eidos Therapeutics, a BridgeBio company |
Amyloidosis|Amyloid Cardiomyopathy|Transthyretin Amyloidosis|Cardiomyopathies|Heart Diseases
|
March 19, 2019 | Phase 3 |
| NCT04958135 | Alexion Pharmaceuticals|Celerion |
Healthy
|
June 16, 2021 | Phase 1 |
| NCT03294707 | Eidos Therapeutics, a BridgeBio company|Celerion |
Amyloid Cardiomyopathy, Transthyretin-Related
|
September 11, 2017 | Phase 1 |
| NCT03536767 | Eidos Therapeutics, a BridgeBio company |
Amyloid Cardiomyopathy
|
August 8, 2018 | Phase 2 |
| NCT04418024 | Eidos Therapeutics, a BridgeBio company |
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
|
October 21, 2020 | Phase 3 |
| NCT04988386 | Eidos Therapeutics, a BridgeBio company |
Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy
|
October 27, 2021 | Phase 3 |
| NCT03458130 | Eidos Therapeutics, a BridgeBio company |
Familial ATTR-CM (ATTRm-CM, or FAC)|Wild-type ATTR-CM (ATTRwt-CM)
|
April 27, 2018 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 62.5 mg/mL ( 190.10 mM ; Need ultrasonic)
H 2 O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.0416 mL | 15.2082 mL | 30.4164 mL |
| 5 mM | 0.6083 mL | 3.0416 mL | 6.0833 mL |
| 10 mM | 0.3042 mL | 1.5208 mL | 3.0416 mL |
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.
- [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.