| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
MK-28 targets the PERK (EIF2AK3) kinase, a key component of the unfolded protein response (UPR) pathway. PERK activation leads to the phosphorylation of eIF2α, which attenuates global protein synthesis and promotes adaptive signaling to alleviate ER stress. MK-28 is highly selective, showing little or no effect on EIF2AK1 (HRI) or EIF2AK2 (PKR), and only weakly activating EIF2AK4 (GCN2) with an EC50 of 3.5 μM. It demonstrates PERK selectivity on a 391-kinase panel.
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| 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].
MK-28 rescues cells from ER stress-induced apoptosis in STHdhQ111/111 cells at concentrations of 0-100 μM. It shows PERK selectivity in vitro on a 391-kinase panel, but not in PERK−/− cells. ATF4 protein levels are significantly increased (up to 2.5-fold) in STHdhQ111/111 cells at high concentrations, while CHOP and GADD34 mRNA levels show increases up to 10- and 5-fold, respectively. MK-28 exhibits an IC50 approximately 3-fold higher than CCT020312 in rescuing mutant huntingtin protein (mHtt)-expressing striatal neurons from apoptosis. |
| 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].
In R6/2 mice, MK-28 (1 mg/kg, IP, daily for 28 days) improves systemic function, increases survival rate, and induces increased levels of eIF2α-P in the mouse brain striatum. Transient subcutaneous delivery significantly improves motor and executive functions and delays death onset in R6/2 mice, showing no toxicity. MK-28 also shows a significant killing effect on MK28 gastric cancer cells. |
| Enzyme Assay |
PERK kinase activity assays are performed using recombinant PERK enzyme and appropriate peptide substrates in the presence of ATP. The assay typically employs a fluorescence-based or radiometric format to measure kinase activity. MK-28 is incubated with the enzyme, substrate, and ATP in assay buffer for 30-60 minutes. The reaction is stopped and product formation is quantified. EC50 values are calculated from concentration-response curves. Selectivity is assessed by screening MK-28 against a panel of 391 kinases.
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| 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. STHdhQ111/111 cells are seeded in multi-well plates and treated with MK-28 at concentrations ranging from 0-100 μM for 48 hours. Cell viability and apoptosis are assessed to evaluate the compound's ability to rescue cells from ER stress-induced apoptosis. ATF4 protein levels are measured by Western blot, while CHOP and GADD34 mRNA levels are quantified by qPCR. The selectivity of MK-28 is confirmed by testing in PERK−/− cells, where no rescue effect is observed. |
| 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. In vivo efficacy is evaluated in R6/2 transgenic mouse models of Huntington's disease. Mice are administered MK-28 at 1 mg/kg via intraperitoneal (IP) injection daily for 28 days. Motor and executive functions are assessed using behavioral tests, and survival rates are monitored. Pharmacodynamic markers such as eIF2α phosphorylation levels are measured in brain tissue (striatum) to confirm target engagement. For pharmacokinetic studies, a single dose of 10 mg/kg IP is administered. |
| ADME/Pharmacokinetics |
MK-28 exhibits remarkable pharmacokinetic properties in mice. Following a single intraperitoneal injection of 10 mg/kg, the compound reaches a maximum plasma concentration (Cmax) of 105 ng/mL, with a plasma half-life of 30 minutes at 40 minutes post-injection. MK-28 demonstrates high blood-brain barrier (BBB) penetration. The compound is soluble in DMSO (12.5 mg/mL) and can be formulated for in vivo administration using 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline.
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| Toxicity/Toxicokinetics |
MK-28 shows no toxicity in R6/2 mice at the tested doses, with transient subcutaneous delivery improving motor and executive functions and delaying death onset. The compound's safety profile supports its use as a research tool for studying PERK activation and UPR signaling. Standard preclinical safety assessments would be required for any therapeutic development. The compound should be handled with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
MK-28 is a potent and selective activator of PERK (EIF2AK3) with an EC50 of 490 nM. It is also known as a PERK agonist that reduces toxicity and prolongs survival in Huntington's disease models. The compound's high BBB penetration and favorable pharmacokinetic profile make it a promising candidate for treating neurodegenerative diseases. MK-28 is a research-use only compound for studying the unfolded protein response and ER stress-related disorders.
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| Molecular Formula |
C24H20N4O2
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|---|---|
| Molecular Weight |
396.44
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| Exact Mass |
396.158
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| CAS # |
864388-65-8
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| PubChem CID |
135425028
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
521
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C=CC(C2=NC(N(/N=C/C3=CC(=C(C=C3)O)O)C)=NC(C3C=CC=CC=3)=C2)=CC=1
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| InChi Key |
GKOVHCFOVLXKFL-XYGWBWBKSA-N
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| 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-
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| Chemical Name |
4-[(Z)-[(4,6-diphenylpyrimidin-2-yl)-methylhydrazinylidene]methyl]benzene-1,2-diol
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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 |
| 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 : 12.5 mg/mL (31.53 mM)
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| 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 |
*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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