Physicochemical Properties
| Molecular Formula | C24H20N4O2 |
| Molecular Weight | 396.44 |
| Exact Mass | 396.158 |
| CAS # | 864388-65-8 |
| PubChem CID | 135425028 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.9 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 30 |
| Complexity | 521 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1C=CC(C2=NC(N(/N=C/C3=CC(=C(C=C3)O)O)C)=NC(C3C=CC=CC=3)=C2)=CC=1 |
| InChi Key | GKOVHCFOVLXKFL-XYGWBWBKSA-N |
| InChi Code | InChI=1S/C24H20N4O2/c1-28(25-16-17-12-13-22(29)23(30)14-17)24-26-20(18-8-4-2-5-9-18)15-21(27-24)19-10-6-3-7-11-19/h2-16,29-30H,1H3/b25-16- |
| Chemical Name | 4-[(Z)-[(4,6-diphenylpyrimidin-2-yl)-methylhydrazinylidene]methyl]benzene-1,2-diol |
| 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 |
| 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 Vitro | MK-28 (0-100 μM) rescues cells from ER stress-induced apoptosis and demonstrates PERK selectivity in vitro on a 391-kinase panel (but not PERK−/− cells)[1]. When MK-28 concentrations are high, ATF4 protein levels in STHdhQ111/111 cells grow significantly—up to a 2.5-fold increase. Both cell types exhibit a significant rise in CHOP and GADD34 mRNA levels, up to 10- and 5-fold, respectively[1]. MK-28 activates EIF2AK4 (GCN2) but has little or no effect on EIF2AK1 (HRI) or EIF2AK2 (PKR)[1]. |
| ln Vivo | MK-28 (10 mg/kg, IP, single dose) exhibits a 40-minute half-life in plasma and a maximal concentration (Cmax) of 105 ng/ml[1]. MK-28 (1 mg/kg, IP, daily for 28 days) increases eIF2α-P levels in the mouse brain striatum and enhances survival and systemic function in R6/2 mice[1]. In R6/2 mice, MK-28 (transient subcutaneous administration) exhibits no toxicity and considerably enhances motor and executive functions as well as delaying the start of death[1]. |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: STHdhQ111/111 cells. Tested Concentrations: 0-100 μM. Incubation Duration: 48 h. Experimental Results: Rescued cells from ER stress-induced apoptosis. |
| Animal Protocol |
Animal/Disease Models: R6/2 mice[1]. Doses: 1 mg/ kg. Route of Administration: IP, daily for 28 days. Experimental Results: Incerased the survival. |
| References |
[1]. A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models. Sci Rep. 2020 Apr 23;10(1):6875. |
Solubility Data
| Solubility (In Vitro) | DMSO : 12.5 mg/mL (31.53 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (3.15 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |