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| 5mg |
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| Targets |
AMG PERK 44 targets PERK (protein kinase RNA-like ER kinase), a key sensor of endoplasmic reticulum (ER) stress. It is a highly selective inhibitor with an IC50 of 6 nM. It exhibits 1000-fold and 160-fold selectivity over GCN2 and B-Raf, respectively. By inhibiting PERK, it modulates the unfolded protein response (UPR), leading to the induction of autophagy and impacting cancer cell survival.
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| ln Vitro |
The half-life of AMG PERK 44 against cellular pPERK is 84 nM [1].
In vitro, AMG PERK 44 potently inhibits PERK with an IC50 of 6 nM. It shows high selectivity, being 1000-fold and 160-fold more selective for PERK than for GCN2 and B-Raf, respectively. The half-life of AMG PERK 44 against cellular pPERK is 84 nM. It induces autophagy in cancer cells, making it a valuable tool for studying the role of PERK in cancer biology and the UPR. |
| ln Vivo |
In this assay, AMG PERK 44 (oral; 3-100 mg/kg) maintains >50% Target coverage was sustained for 24 hours in a time-course PD assay when administered at 100 mg/kg po. It also potently inhibits PERK autophosphorylation (ED50=3 mg/kg; 4-hour time point ED90=60 mg/kg) [1]. In male CD-1 mice and Sprague-Dawley rats, AMG PERK 44 (iv; 1 mg/kg) has an MRT of 2.3 hours, a CL of 1.6 L/h·kg, and a Vss of 3.6 L/kg [1].
In vivo, AMG PERK 44 is orally active. In a time-course pharmacodynamic (PD) assay, oral administration at 100 mg/kg maintained >50% target coverage for 24 hours. This demonstrates its potential for sustained target inhibition in vivo. It is used in cancer research to study the effects of PERK inhibition on tumor growth and the UPR. |
| Enzyme Assay |
In vitro enzyme assays for AMG PERK 44 involve kinase inhibition studies using recombinant PERK. The kinase is incubated with increasing concentrations of the compound, ATP, and a specific peptide substrate. Phosphorylation is measured using radioactive ³³P-ATP or through luminescence-based assays. IC50 values are calculated from dose-response curves. Selectivity is confirmed by testing the compound against a panel of kinases, including GCN2 and B-Raf.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines are cultured and treated with AMG PERK 44. PERK inhibition is confirmed by measuring the phosphorylation of its downstream substrate, eIF2α, by Western blot. Autophagy induction is assessed by measuring LC3-II levels. Cell viability and proliferation are measured by MTT or CellTiter-Glo assays. The compound's effects on the UPR and cell survival are evaluated.
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| Animal Protocol |
Animal/Disease Models: SD (SD (Sprague-Dawley)) rats and male CD-1 mice [1]
Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection Experimental Results: CL is 1.6 L/h·kg, Vss is 3.6 L/kg, 2.3 hrs (hrs (hours)) on the subway. In vivo animal studies with AMG PERK 44 are conducted in mouse xenograft models of cancer. The compound is administered orally at doses such as 3-100 mg/kg. Target coverage is assessed by measuring PERK activity in tumor tissues. Tumor growth inhibition is monitored. Pharmacodynamic markers, such as p-eIF2α and autophagy markers, are analyzed in harvested tumors. Its oral bioavailability and sustained target coverage are key features. |
| ADME/Pharmacokinetics |
AMG PERK 44 (CAS: 1883548-84-2) has a molecular weight of 561.07 g/mol and a molecular formula of C34H29ClN4O2. It is also known as 4-[2-amino-4-methyl-3-(2-methylquinolin-6-yl)benzoyl]-1-methyl-2,5-diphenyl-2,3-dihydro-1H-pyrazol-3-one hydrochloride. It is a solid and is soluble in DMSO. Storage is typically at -20°C, sealed, and away from moisture.
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| Toxicity/Toxicokinetics |
AMG PERK 44 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a PERK inhibitor, it may have effects on normal tissues that rely on the UPR for protein homeostasis. However, its high selectivity suggests a favorable therapeutic window. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
AMG PERK 44 is a highly selective and orally active PERK inhibitor with an IC50 of 6 nM. It exhibits 1000-fold and 160-fold selectivity over GCN2 and B-Raf, respectively. It induces autophagy and is used for cancer research. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C34H29CLN4O2
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|---|---|
| Molecular Weight |
561.072666883469
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| Exact Mass |
560.197
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| CAS # |
1883548-84-2
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| PubChem CID |
121513867
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
41
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| Complexity |
967
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C1C(C(C2C=CC(C)=C(C3C=CC4C(=CC=C(C)N=4)C=3)C=2N)=O)=C(C2C=CC=CC=2)N(C)N1C1C=CC=CC=1
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| InChi Key |
RNAKBTDDCHJCMT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H28N4O2.ClH/c1-21-14-18-27(31(35)29(21)25-17-19-28-24(20-25)16-15-22(2)36-28)33(39)30-32(23-10-6-4-7-11-23)37(3)38(34(30)40)26-12-8-5-9-13-26;/h4-20H,35H2,1-3H3;1H
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| Chemical Name |
4-[2-amino-4-methyl-3-(2-methylquinolin-6-yl)benzoyl]-1-methyl-2,5-diphenylpyrazol-3-one;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~44.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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