KZR-504 is a novel, potent and highly selective inhibitor of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) subunit with a potential for the treatment of autoimmune disease.
Physicochemical Properties
| Molecular Formula | C21H23N3O6 |
| Molecular Weight | 413.423825502396 |
| Exact Mass | 413.158 |
| CAS # | 1629052-78-3 |
| Related CAS # | 1629052-78-3; |
| PubChem CID | 117611788 |
| Appearance | White to off-white solid powder |
| LogP | 0 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 30 |
| Complexity | 771 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | O1C[C@]1(C)C([C@H](CC1C=CC=CC=1)NC([C@H](CO)NC(C1=CC=CC(N1)=O)=O)=O)=O |
| InChi Key | QYDASSGXBXGRBS-CKJXQJPGSA-N |
| InChi Code | InChI=1S/C21H23N3O6/c1-21(12-30-21)18(27)15(10-13-6-3-2-4-7-13)23-20(29)16(11-25)24-19(28)14-8-5-9-17(26)22-14/h2-9,15-16,25H,10-12H2,1H3,(H,22,26)(H,23,29)(H,24,28)/t15-,16-,21+/m0/s1 |
| Chemical Name | N-((S)-3-Hydroxy-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxamide |
| Synonyms | KZR-504 KZR 504 KZR504 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
Biological Activity
| ln Vivo | Compounded with anti-targets LMP7 and β5, evaluation of LMP2 inhibition in mouse tissues revealed that KZR-504 (compound 12) exhibits potent and selective in vivo effects in all examined tissues (except from the brain) at >1 mg/ >50% target inhibition at doses of kg [1]. |
| References |
[1]. Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) Subunit. ACS Med Chem Lett. 2017 Mar 9;8(4):413-417. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~170 mg/mL (~411.20 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (10.28 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 42.5 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: ≥ 4.25 mg/mL (10.28 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 42.5 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. Solubility in Formulation 3: ≥ 4.25 mg/mL (10.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4188 mL | 12.0942 mL | 24.1885 mL | |
| 5 mM | 0.4838 mL | 2.4188 mL | 4.8377 mL | |
| 10 mM | 0.2419 mL | 1.2094 mL | 2.4188 mL |