MRK-016

Name: MRK-016
Brand: MedChemExpress
SKU: HY-100370
Rating: 4.5 (1 reviews)

Cat. No.: HY-100370 Purity: 99.71%: FAQs
Data Sheet SDS COA Handling Instructions

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MRK-016 is a selective, orally bioavailable inverse agonist of GABA_A α5 receptor, with an EC₅₀ of 3 nM for GABA_A α5, and K_is of 0.83, 0.85, 0.77?and 1.4?nM for human?GABA_A?α1β3γ2, GABA_A?α2β3γ2, GABA_A?α3β3γ2, and GABA_A?α5β3γ2, respectively; MRK-016 also readily penetrates the CNS.

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

MRK-016 Chemical Structure

CAS No. : 342652-67-9

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 132	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 132	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 120	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 190	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 750	In-stock	Estimated Time of Arrival: December 31
100 mg		Get quote
200 mg		Get quote

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Customer Review

Based on 1 publication(s) in Google Scholar

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Description

IC₅₀ & Target

EC50: 3 nM (GABA_A α5)^[1]
Ki: 0.83 nM (Human GABA_A α1β3γ2), 0.85 nM (Human GABA_A α2β3γ2), 0.77 nM (Human GABA_A α3β3γ2), 1.4 nM (Human GABA_A α5β3γ2)^[1]

In Vitro

MRK-016 is a selective, orally bioavailable inverse agonist of GABA_A α5 receptor, with an EC₅₀ of 3 nM for GABA_A α5, and K_is of 0.83, 0.85, 0.77?and 1.4?nM for human?GABA_A?α1β3γ2, GABA_A?α2β3γ2, GABA_A?α3β3γ2, and GABA_A?α5β3γ2, respectively^[1]^[2]. MRK-016 is a full inverse agonist at the α5-subtype, shows very weak affinity at the GABA_A α4β3γ2-subtype (K_i 395 ± 173 nM) and is essentially inactive at the GABA_A α6β3γ2 receptor (K_i > 4000 nM)^[1]. MRK-016 shows a weak effect on GABA_A?α4β3γ2 with a K_i of 400 nM. MRK-016 (100 nM) alao increases long-term potentiation in mouse hippocampal slices^[2].

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

In Vivo

MRK-016 does not enhance pentylenetetrazole-induced convulsions at 10 mg/kg via ip, or cause seizures at 30 mg/kg, via po for 20 days in mice. MRK-016 shows no obvious anxiogenic-like effects in rats at doses that occupy >95% of benzodiazepine (BZ) binding sites. MRK-016 (0.3, 1, and 3 mg/kg, p.o.) dose-dependently improves performance of rats hippocampal-dependent memory task^[1]. MRK-016 (0.3-30 mg/kg, p.o.) causes good receptor occupancy in rats. MRK-016 (0.3, 1, or 3 mg/kg p.o.) shows cognition-enhancing activity in the delayed matching-to-position version of the Morris water maze. MRK-016 (1, 3, or 10 mg/kg i.p.) does not produce kindling in mice^[2]. MRK-016 (3 mg/kg, i.p.) protects against LPS-induced learning/memory decrements in mice^[3].

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

Molecular Weight

368.39

Formula

C₁₇H₂₀N₈O₂

CAS No.

342652-67-9

Appearance

Solid

Color

White to off-white

SMILES

CN1N=CN=C1COC2=NN3C(C4=NOC(C)=C4)=NN=CC3=C2C(C)(C)C

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL (135.73 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	2.7145 mL	13.5726 mL	27.1451 mL
5 mM	0.5429 mL	2.7145 mL	5.4290 mL
10 mM	0.2715 mL	1.3573 mL	2.7145 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
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: ≥ 2.75 mg/mL (7.46 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 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: ≥ 2.75 mg/mL (7.46 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 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: ≥ 2.75 mg/mL (7.46 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 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 (27.5 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: 99.71%

Select Batch:

Data Sheet (282 KB) SDS (393 KB)

COA (255 KB) LCMS (93 KB) Elemental Analysis Report (113 KB)

Handling Instructions (2659 KB)

References

[1]. Chambers MS, et al. An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties. J Med Chem. 2004 Nov 18;47(24):5829-32. [Content Brief]

[2]. Atack JR, et al. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84. [Content Brief]

[3]. Eimerbrink MJ, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res. 2015 Jul 15;288:50-3. [Content Brief]

Kinase Assay ^[1]	L(tk^-) cells expressing human recombinant GABA_A receptors containing β3- and γ2-subunits in combinatioon with various α-subunits are harvested and binding performed. The displacement of [³H]Ro 15-1788 binding by the test compounds (MRK-016, etc.) is measured in GABA_A receptors containing eigher an α1-, α2-, α3-, and α5-subunit and from the IC₅₀ and the K_i is calculated assuming respective K_d values of [³H]Ro 15-1788 binding of 0.92, 1.05, 0.58 and 0.45 nM at the α1-, α2-, α3-, and α5-subtypes. Nonspecific binding is defined by the inclusion of 10 μM flunitrazepam for the α1-, α2-, α3-, and α5-subtypes. The percentage inhibition of [³H]Ro 15-1788, the IC₅₀ and the K_i values are calculated using ActivityBase^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] The proconvulsant potential MRK-016 is determined in this assay. The convulsant is pentylenetetrazole which is dosed at 15 mg/mL with an infusion rate of 0.2 mL/min. This rate is chosen to ensure that drug-naive mince reach the terminal convulsion sign within 1 min. MRK-016 is dosed intraperitoneally (ip) at a concentration of 1, 3, and 10 mg/kg in 70% PEG 300^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Chambers MS, et al. An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties. J Med Chem. 2004 Nov 18;47(24):5829-32. [Content Brief] [2]. Atack JR, et al. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84. [Content Brief] [3]. Eimerbrink MJ, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res. 2015 Jul 15;288:50-3. [Content Brief]

Complete Stock Solution Preparation Table

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

DMSO	1 mM	2.7145 mL	13.5726 mL	27.1451 mL	67.8629 mL
	5 mM	0.5429 mL	2.7145 mL	5.4290 mL	13.5726 mL
	10 mM	0.2715 mL	1.3573 mL	2.7145 mL	6.7863 mL
	15 mM	0.1810 mL	0.9048 mL	1.8097 mL	4.5242 mL
	20 mM	0.1357 mL	0.6786 mL	1.3573 mL	3.3931 mL
	25 mM	0.1086 mL	0.5429 mL	1.0858 mL	2.7145 mL
	30 mM	0.0905 mL	0.4524 mL	0.9048 mL	2.2621 mL
	40 mM	0.0679 mL	0.3393 mL	0.6786 mL	1.6966 mL
	50 mM	0.0543 mL	0.2715 mL	0.5429 mL	1.3573 mL
	60 mM	0.0452 mL	0.2262 mL	0.4524 mL	1.1310 mL
	80 mM	0.0339 mL	0.1697 mL	0.3393 mL	0.8483 mL
	100 mM	0.0271 mL	0.1357 mL	0.2715 mL	0.6786 mL

MRK-016 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-016342652-67-9MRK016MRK 016GABA ReceptorGamma-aminobutyric acid Receptorγ-Aminobutyric acid ReceptorInhibitorinhibitorinhibit

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MRK-016

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