| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The primary target of MRK-560 is γ-secretase, specifically presenilin-1 (PSEN1)-containing complexes. It is a potent and selective γ-secretase inhibitor. MRK-560 effectively blocks amyloid-β (Aβ) peptide formation, making it a valuable tool for Alzheimer's disease research. It inhibits γ-secretase with an IC₅₀ of 0.65 nM in SH-SY5Y neuroblastoma cells.
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| ln Vitro |
In human T-ALL cell lines, MRK-560 (30, 100, 300, and 1000 nM; 15 days) inhibits mutant NOTCH1 receptor signaling [1].
In vitro, MRK-560 potently inhibits γ-secretase activity with an IC₅₀ of 0.65 nM in SH-SY5Y neuroblastoma cells. It selectively inhibits APP cleavage over the Notch pathway. This selectivity is important for reducing potential Notch-related toxicities. |
| ln Vivo |
In the T-ALL model, MRK-560 (15.54 mg/kg; SC; once daily for 14 days) has potent anti-leukemia actions [1]. In a dose-dependent way, MRK-560 (1, 3, 10, 30, 100 mg/kg; oral; single dose) exhibits good blood-brain barrier permeability in rats [2]. The oral single-dose medication MRK-560 (1, 3, 10, 30, 100 mg/kg) reduces the brain's and cerebrospinal fluid's ability to produce Aβ [2]. With a Tmax of 12 hours, MRK-560 (1 mg/kg; oral; single dosage) exhibits high bioavailability of 70 to 90% [2]. A once-daily dosage of MRK-560 (1 mg/kg; IV; single dose) is appropriate due to its low plasma clearance and longer half-life than 15 hours [2].
In vivo, MRK-560 markedly reduces Aβ peptide levels in the brain and CSF of rats. It is orally bioavailable and brain-penetrant. It attenuates plaque deposition in animal models. The compound confirms the utility of the rat for assessing the effects of γ-secretase inhibitors on CNS Aβ levels. |
| Enzyme Assay |
For in vitro enzyme assays, MRK-560 is tested against γ-secretase. Standard protocols involve incubating the enzyme with a substrate (e.g., APP-derived peptide) and varying concentrations of MRK-560 (0.01-100 nM). Aβ production is measured by ELISA or immunodetection. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HPB-ALL, DND-41 and Jurkat Cell Tested Concentrations: 30, 100, 300, 1000 nM Incubation Duration: 15 days Experimental Results: diminished NICD1 production in cells and resulted in dose-dependent reduction of HPB -ALL and DND-41 proliferation, whose survival depends on NOTCH signaling. Cell-based assays for MRK-560 involve treating cells (e.g., SH-SY5Y neuroblastoma cells) with the compound at concentrations of 0.01-100 nM for 24-48 hours. Aβ production is measured by ELISA. Selectivity for APP over Notch is assessed by measuring Notch signaling or Notch intracellular domain levels. |
| Animal Protocol |
Animal/Disease Models: Tg(HLA-DRB1)31Dmz/Szj(NSG) mouse (T-ALL (T-cell acute lymphoblastic leukemia) model) [1].
Doses: 15.54 mg/kg Route of Administration: subcutaneous injection; one time/day for 14 days. Experimental Results: A strong antileukemic effect was produced and the median survival of vehicle-treated mice was increased from 18 to 30 days. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (250-300 g) [2]. Doses: 1, 3, 10, 30, 100 mg/kg Route of Administration: Oral; single dose (experiment conducted after 8 hrs (hrs (hours))) Experimental Results: Plasma and brain concentrations increased in a dose-dependent manner. Brain and cerebrospinal fluid Aβ levels were diminished (dose-dependently), with an essentially complete inhibition of the production of both peptides observed at the 100 mg/kg dose. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (250-300 g) [2]. Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)and oral; single. Experimental Results: Tmax was reached 12 hrs (hrs (hours)) after oral administration, and the bioavailability was 70 to 90%. Plasma clearance was shown to be less tha In vivo studies with MRK-560 are conducted in rodent models. Typical protocols involve oral administration at doses of 1-10 mg/kg. Aβ levels in brain and CSF are measured by ELISA. Plaque deposition is assessed in transgenic Alzheimer's models. Efficacy is determined by reduction in Aβ levels and plaque burden. |
| ADME/Pharmacokinetics |
MRK-560 is orally bioavailable and brain-penetrant. It markedly reduces Aβ peptide in the brain and CSF of rats. Detailed PK parameters including oral bioavailability, half-life, and brain penetration are available from research publications.
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| Toxicity/Toxicokinetics |
Toxicology data for MRK-560 are available from preclinical studies. The compound is well-tolerated at therapeutic doses. The selective inhibition of PSEN1 over PSEN2 may reduce toxicity associated with pan-γ-secretase inhibitors. Comprehensive toxicology data are available from research publications.
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| References |
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| Additional Infomation |
MRK-560 is a potent and selective γ-secretase inhibitor used in Alzheimer's disease research. It selectively inhibits APP cleavage over the Notch pathway. It targets presenilin-1-containing complexes while sparing presenilin-2. No FDA approvals exist.
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| Molecular Formula |
C19H17CLF5NO4S2
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|---|---|
| Molecular Weight |
517.92
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| Exact Mass |
517.021
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| Elemental Analysis |
C, 44.06; H, 3.31; Cl, 6.85; F, 18.34; N, 2.70; O, 12.36; S, 12.38
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| CAS # |
677772-84-8
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| PubChem CID |
11577204
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| Appearance |
white solid powder
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| LogP |
7.221
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
856
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(C=CC(=C1)S(=O)(=O)[C@@]2(CC[C@@H](CC2)NS(=O)(=O)C(F)(F)F)C3=C(C=CC(=C3)F)F)Cl
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| InChi Key |
WDZVWDXOIGQJIO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17ClF5NO4S2/c20-12-1-4-15(5-2-12)31(27,28)18(16-11-13(21)3-6-17(16)22)9-7-14(8-10-18)26-32(29,30)19(23,24)25/h1-6,11,14,26H,7-10H2
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| Chemical Name |
N-[4-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide
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| Synonyms |
MRK-560; MRK 560; MRK560
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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 : ~100 mg/mL (~193.08 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.83 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 25.0 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: ≥ 2.5 mg/mL (4.83 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 25.0 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: ≥ 2.5 mg/mL (4.83 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 | 1.9308 mL | 9.6540 mL | 19.3080 mL | |
| 5 mM | 0.3862 mL | 1.9308 mL | 3.8616 mL | |
| 10 mM | 0.1931 mL | 0.9654 mL | 1.9308 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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