342652-67-9
342652-67-9 structure
- Name: MRK 016
- Chemical Name: MRK-016
- CAS Number: 342652-67-9
- Molecular Formula: C17H20N8O2
- Molecular Weight: 368.39
- Catalog: Signaling Pathways Membrane Transporter/Ion Channel GABA Receptor
- Create Date: 2018-05-30 20:32:47
- Modify Date: 2024-01-02 16:45:08
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MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively; MRK-016 also readily penetrates the CNS.
| Name | MRK-016 |
|---|---|
| Synonyms |
3-tert-butyl-7-(5-methyl-1,2-oxazol-3-yl)-2-[(1-methyl-1H-1,2,4-triazol-5-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine
7-(5-Methyl-1,2-oxazol-3-yl)-3-(2-methyl-2-propanyl)-2-[(1-methyl-1H-1,2,4-triazol-5-yl)methoxy]pyrazolo[1,5-d][1,2,4]triazine Pyrazolo[1,5-d][1,2,4]triazine, 3-(1,1-dimethylethyl)-7-(5-methyl-3-isoxazolyl)-2-[(1-methyl-1H-1,2,4-triazol-5-yl)methoxy]- 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 |
| Description | MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively; MRK-016 also readily penetrates the CNS. |
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| Related Catalog | |
| Target |
EC50: 3 nM (GABAA α5)[1] Ki: 0.83 nM (Human GABAA α1β3γ2), 0.85 nM (Human GABAA α2β3γ2), 0.77 nM (Human GABAA α3β3γ2), 1.4 nM (Human GABAA α5β3γ2)[1] |
| In Vitro | MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively[1][2]. MRK-016 is a full inverse agonist at the α5-subtype, shows very weak affinity at the GABAA α4β3γ2-subtype (Ki 395 ± 173 nM) and is essentially inactive at the GABAA α6β3γ2 receptor (Ki > 4000 nM)[1]. MRK-016 shows a weak effect on GABAA α4β3γ2 with a Ki of 400 nM. MRK-016 (100 nM) alao increases long-term potentiation in mouse hippocampal slices[2]. |
| 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]. |
| Kinase Assay | L(tk-) cells expressing human recombinant GABAA 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 GABAA receptors containing eigher an α1-, α2-, α3-, and α5-subunit and from the IC50 and the Ki is calculated assuming respective Kd 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 Ki values are calculated using ActivityBase[1]. |
| Animal Admin | 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]. |
| References |
| Molecular Formula | C17H20N8O2 |
|---|---|
| Molecular Weight | 368.39 |
| Storage condition | 2-8℃ |