MRK-560

Name: MRK-560
Brand: MedChemExpress
SKU: HY-14174
Rating: 4.5 (1 reviews)

Cat. No.: HY-14174 Purity: 99.51%: FAQs
Data Sheet SDS COA Handling Instructions

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MRK-560 is an orally active, brain barrier-penetrating γ-Secretase inhibitor, can potently reduce Aβ peptide in rat brain and cerebrospinal fluid. MRK-560 also decreases mutant NOTCH1 processing by selectively inhibiting PSEN1. MRK-560 can be used in studies of Alzheimer's disease and T-cell acute lymphoblastic leukaemia (T-ALL).

For research use only. We do not sell to patients.

MRK-560 Chemical Structure

CAS No. : 677772-84-8

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 80	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 80	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 70	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 110	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 220	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 360	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 580	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 1 publication(s) in Google Scholar

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References
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Description

IC₅₀ & Target

γ-secretase, PSEN1^[1]^[2].

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	14.3 nM Compound: MRK-560	Inhibition of gamma-secretase in HEK293 cell membranes using SPC99-Lon as substrate assessed as formation of amyloid beta 40 after 1 hr by electrochemiluminescence-based immunoassay Inhibition of gamma-secretase in HEK293 cell membranes using SPC99-Lon as substrate assessed as formation of amyloid beta 40 after 1 hr by electrochemiluminescence-based immunoassay	[PMID: 26496070]
HEK293	IC₅₀	15 nM Compound: MRK-560	Inhibition of gamma-secretase in HEK293 cells using human APP Swedish/London double mutant as substrate assessed as formation of amyloid beta 40 after 5 to 6 hrs by sandwich immunoassay Inhibition of gamma-secretase in HEK293 cells using human APP Swedish/London double mutant as substrate assessed as formation of amyloid beta 40 after 5 to 6 hrs by sandwich immunoassay	[PMID: 26496070]
HEK293	IC₅₀	5 nM Compound: MRK-560	Inhibition of gamma-secretase in HEK293 cells using human APP Swedish/London double mutant as substrate assessed as formation of amyloid beta 42 after 5 to 6 hrs by sandwich immunoassay Inhibition of gamma-secretase in HEK293 cells using human APP Swedish/London double mutant as substrate assessed as formation of amyloid beta 42 after 5 to 6 hrs by sandwich immunoassay	[PMID: 26496070]

In Vitro

MRK-560 (30, 100, 300, 1000 nM; 15days) blocks mutant NOTCH1 receptor signaling in human T-ALL cell lines^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay^[1]

Cell Line:	HPB-ALL, DND-41, and Jurkat cells
Concentration:	30, 100, 300, 1000 nM
Incubation Time:	15 days
Result:	Reduced NICD1 generation in cells and resulted in a dose-dependent decrease of proliferation in HPB-ALL and DND-41, which depend on NOTCH signaling for their survival.

In Vivo

MRK-560 (15.54 mg/kg; S.C.; single daily for 14 days) shows strong antileukemic effects on T-ALL model^[1].
MRK-560 (1, 3, 10, 30, 100 mg/kg; p.o.; single) shows good blood-brain barrier permeability in a dose-dependent manner in rats^[2].

MRK-560 (1, 3, 10, 30, 100 mg/kg; p.o.; single) inhibits the production of Aβ levels in brain and cerebrospinal fluid^[2].
MRK-560 (1 mg/kg; p.o.; single) shows a good bioavailability of 70 to 90%, and T_max is 12 h^[2].
MRK-560 (1 mg/kg; i.v.; single) is suitable for once-a-day dosing (with a low plasma clearance and a half-life of more than 15 h)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Tg (HLA-DRB1) 31Dmz/Szj (NSG) mice (T-ALL (T cell acute lymphoblastic leukemia) model)^[1].
Dosage:	15.54 mg/kg
Administration:	Subcutaneous injection; single daily for 14 days.
Result:	Resulted in strong antileukemic effects and improved median survival to 30 days compared to 18 days in vehicle-treated mice.

Animal Model:	Male Sprague-Dawley rats (250-300 g)^[2].
Dosage:	1, 3, 10, 30, 100 mg/kg
Administration:	Oral administration; single (experiment is performed 8 h later)
Result:	Increased the plasma and brain concentrations in a dose-dependent manner. Reduced (dose-dependent) both brain and CSF Aβ levels, with essentially complete inhibition of the production of both peptides being observed at a dose of 100 mg/kg.

Animal Model:	Male Sprague-Dawley rats (250-300 g)^[2].
Dosage:	1 mg/kg
Administration:	Intravenously and orally administration; single.
Result:	Showed T_max after the oral dose was 12 h,and bioavailability was 70 to 90%. Revealed a low plasma clearance of less than 5 mL/min/kg with a volume of distribution of approximately 6 L/kg, which translated to a long half-life of more than 15 h.

Molecular Weight

517.92

Formula

C₁₉H₁₇ClF₅NO₄S₂

CAS No.

677772-84-8

Appearance

Solid

Color

White to off-white

SMILES

O=S([C@]1(C2=C(C=CC(F)=C2)F)CC[C@H](NS(C(F)(F)F)(=O)=O)CC1)(C3=CC=C(Cl)C=C3)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (193.08 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.51%

Select Batch:

Data Sheet (281 KB) SDS (393 KB)

COA (253 KB) LCMS (88 KB)

Handling Instructions (2659 KB)

References

[1]. Habets RA, et al. Safe targeting of T cell acute lymphoblastic leukemia by pathology-specific NOTCH inhibition. Sci Transl Med. 2019 May 29;11(494):eaau6246. [Content Brief]

[2]. Best JD, et al. In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in the rat. J Pharmacol Exp Ther.2006 May;317(2):786-90.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.9308 mL	9.6540 mL	19.3080 mL	48.2700 mL
	5 mM	0.3862 mL	1.9308 mL	3.8616 mL	9.6540 mL
	10 mM	0.1931 mL	0.9654 mL	1.9308 mL	4.8270 mL
	15 mM	0.1287 mL	0.6436 mL	1.2872 mL	3.2180 mL
	20 mM	0.0965 mL	0.4827 mL	0.9654 mL	2.4135 mL
	25 mM	0.0772 mL	0.3862 mL	0.7723 mL	1.9308 mL
	30 mM	0.0644 mL	0.3218 mL	0.6436 mL	1.6090 mL
	40 mM	0.0483 mL	0.2414 mL	0.4827 mL	1.2068 mL
	50 mM	0.0386 mL	0.1931 mL	0.3862 mL	0.9654 mL
	60 mM	0.0322 mL	0.1609 mL	0.3218 mL	0.8045 mL
	80 mM	0.0241 mL	0.1207 mL	0.2414 mL	0.6034 mL
	100 mM	0.0193 mL	0.0965 mL	0.1931 mL	0.4827 mL

MRK-560 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MRK-560677772-84-8MRK560MRK 560γ-secretaseGamma secretaseAβ peptidesAlzheimer’s diseaseT-ALLHPB-ALLDND-41Jurkat cellsInhibitorinhibitorinhibit

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