MK-0752 |
Catalog No.GC15899
One-Click Copy Product Info
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A potent inhibitor of γ-secretase
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 471905-41-6
Sample solution is provided at 25 µL, 10mM.
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MK-0752 is a potent gamma secretase inhibitor in clinical development (IC50 ~50 nM). Gamma secretase is an important component in the NOTCH cleavage machinery that catalyzes the cleavage of receptor protein substrates within their transmembrane domain. Inhibition of Notch inhibits BC cell proliferation in vitro. Notch signaling requires gamma secretase, which cleaves Notch, releasing the Notch intracellular domain (NICD) to activate transcription of target genes. NOTCH signaling plays an important role in normal tissue development, cell fate determination, proliferation, and survival. NOTCH signaling is activated following the binding of cognate ligands that include Delta1, Delta2, and Delta3 and Jagged1 and Jagged2.
Reference
[1].I. E. Krop, M. Kosh, I. Fearen, J. Savoie, A. Dallob, C. Matthews, J. Stone, E. Winer, S. J. Freedman and P. Lorusso. Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors. J Clin Oncol (Meeting Abstracts) June 2006 vol. 24 no. 18_suppl 10574.
[2].Maryam Fouladi, Clinton F. Stewart, James Olson, Lars M. Wagner, Arzu Onar-Thomas, Mehmet Kocak, Roger J. Packer, Stewart Goldman, Sridharan Gururangan, Amar Gajjar, Tim Demuth, Larry E. Kun, James M. Boyett and Richard J. Gilbertson. Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study. JCO September 10, 2011 vol. 29 no. 26 3529-3534
| Cell experiment: [1] | |
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Cell lines |
SH-SY5Y cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
IC50: 5 nM. |
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Applications |
As a moderately potent γ-secretase inhibitor, MK-0752 inhibited the production of Aβ40 in a dose-dependent manner with an IC50 of 5 nM in human SH-SY5Y cells. |
| Animal experiment : [1] | |
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Animal models |
Male CMP rhesus monkeys |
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Dosage form |
Oral administration, 60 mg/kg and 240mg/kg |
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Applications |
Oral administration of MK-0752 demonstrated a dose-related reduction of Aβ levels. After 48 h, the Aβ levels with 240mg/kg treatment only recovered to 50%of baseline, while the 60mg/kg treatment group reached baseline at 30 h without overshoot. Plasma Aβ levels rebounded above baseline after MK-0752 inhibition (60 mg/kg, h 33–48). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Cook J J, Wildsmith K R, Gilberto D B, et al. Acute γ-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-β production to alternative APP fragments without amyloid-β rebound[J]. The Journal of Neuroscience, 2010, 30(19): 6743-6750. | |
| Cas No. | 471905-41-6 | SDF | |
| Chemical Name | 3-[4-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid | ||
| Canonical SMILES | C1CC(CCC1CCC(=O)O)(C2=C(C=CC(=C2)F)F)S(=O)(=O)C3=CC=C(C=C3)Cl | ||
| Formula | C21H21ClF2O4S | M.Wt | 442.9 |
| Solubility | ≥ 22.15 mg/mL in DMSO, ≥ 48.8 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2578 mL | 11.2892 mL | 22.5785 mL |
| 5 mM | 451.6 μL | 2.2578 mL | 4.5157 mL |
| 10 mM | 225.8 μL | 1.1289 mL | 2.2578 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)