[CAS NO. 1883548-84-2] AMGPERK44
PRODUCTS SPECIFICATIONS [1883548-84-2]
DESCRIPTION [1883548-84-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 561.07 |
| Molecular Formula | C34H29ClN4O2 |
| SMILES | O=C1N(C2=CC=CC=C2)N(C)C(C3=CC=CC=C3)=C1C(C4=CC=C(C)C(C5=CC=C6N=C(C)C=CC6=C5)=C4N)=O.[H]Cl |
Summary
IC50 & Target
IC50: 6 nM (PERK) [1]
In Vitro
AMG PERK 44 has an IC 50 of 84 nM for cell pPERK [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
AMG PERK 44 (orally; 3-100 mg/kg) robustly inhibits PERK autophosphorylation in this assay (ED
50
=3 mg/kg; ED
90
=60 mg/kg at the 4 hours time point), and >50% target coverage is maintained for 24 h in a time course PD assay when dosed at 100 mg/kg po
[1]
.
AMG PERK 44 (iv; 1 mg/kg) has a CL of 1.6 L/h•kg, a V
ss
of 3.6 L/kg and MRT of 2.3 hours in Sprague-Dawley rats and male CD-1 mice
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Four- to six-week old naive athymic nude mice [1] |
| Dosage: | 3, 10, 30, 100 mg/kg |
| Administration: | Orally |
| Result: | Robustly inhibited PERK autophosphorylation in this assay (ED 50 =3 mg/kg; ED 90 =60 mg/kg at the 4 hours time point). |
| Animal Model: | Sprague-Dawley rats and male CD-1 mice [1] |
| Dosage: | 1 mg/kg (Pharmacokinetic Analysis) |
| Administration: | Iv |
| Result: | Had a CL of 1.6 L/h•kg, a V ss of 3.6 L/kg and a MRT of 2.3 hours. |
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 : 25 mg/mL ( 44.56 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.7823 mL | 8.9115 mL | 17.8231 mL |
| 5 mM | 0.3565 mL | 1.7823 mL | 3.5646 mL |
| 10 mM | 0.1782 mL | 0.8912 mL | 1.7823 mL |
References
- [1] Smith AL, et al. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J Med Chem. 2015 Feb 12;58(3):1426-41.
- [2] Roest G, et al. The ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca2+-Dependent Manner. Cells. 2018 Nov 30;7(12). pii: E239.