| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
human H3 receptor 1.7 nM (IC50) rhesus H3 receptor 4.3 nM (Ki) human H3 receptor 6.8 nM (Ki) rat H3 receptor 33 nM (Ki)
Histamine H3 receptor. |
|---|---|
| ln Vitro |
MK-0249 (Compound 1) is a substrate for rat P-gp but not for human P-gp, and it exhibits very good hepatic clearance values (CLh e 11 mL/min/kg)[1]. MK-0249 exhibits a strong affinity for binding human, rat, and rhesus H3 receptors, as evidenced by its respective Ki values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM[1]. High intrinsic activity is displayed by MK-0249[1].
MK-0249 is a potent H3 receptor antagonist with an IC50 of 1.7 nM for the human H3 receptor. It is selective for the H3 receptor and is orally active. By blocking H3 autoreceptors, it increases histamine release and enhances neurotransmitter activity. |
| ln Vivo |
The rat brain's histamine levels are raised by MK-0249 (Compound 1) (0-30 mg/kg; po; once) in a dose-dependent way[1]. In comparison to mdr1a (+/+) mice, mdr1a (-/-) mice exhibit significantly greater brain penetrability and a lower plasma Occ90 value when exposed to MK-0249 (10 mg/kg; po; once)[1]. In rodents, P-gp mediated efflux greatly limits MK-0249, whereas in humans, this efflux should be very minor or nonexistent[1]. MK-0249 exhibits rat brain permeability.
In vivo, MK-0249 has been studied for its potential in treating attention deficit and hyperactivity disorder (ADHD). As an H3 receptor antagonist, it modulates the histaminergic system and may improve cognitive function, wakefulness, and attention. |
| Enzyme Assay |
In vitro receptor binding assays for MK-0249 are performed to evaluate its affinity for the H3 receptor. Radioligand binding studies using membrane preparations from cells expressing the human H3 receptor are conducted. The compound's ability to displace a specific radiolabeled H3 ligand is measured to calculate its IC50 (1.7 nM).
|
| Cell Assay |
In vitro cell-based assays are conducted using cells expressing the human H3 receptor. The cells are treated with MK-0249, and receptor antagonism is measured by assessing its ability to block H3 receptor-mediated inhibition of cAMP accumulation or neurotransmitter release.
|
| Animal Protocol |
In vivo animal studies are conducted in rodent models to evaluate the effects of MK-0249 on cognitive function, attention, and wakefulness. The compound is typically administered orally, and its effects on behavior and neurotransmitter levels are assessed.
|
| ADME/Pharmacokinetics |
MK-0249 is an orally active compound. Detailed pharmacokinetic parameters such as half-life, bioavailability, and brain penetration are not extensively documented in publicly available literature.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for MK-0249. As an H3 receptor antagonist, its toxicity profile is expected to be related to its mechanism of action. Standard safety precautions should be followed when handling this compound.
|
| References | |
| Additional Infomation |
MK0249 has been used in trials to study the treatment of hypoventilation syndrome, Alzheimer's disease, paranoid schizophrenia, obstructive sleep apnea, and excessive daytime sleepiness.
MK-0249 is a potent, selective, and orally active H3 receptor antagonist with an IC50 of 1.7 nM. It has been studied for its potential in treating attention deficit and hyperactivity disorder (ADHD). The compound is not approved for human therapeutic use and is strictly for research purposes. |
| Molecular Formula |
C23H24F3N3O2
|
|---|---|
| Molecular Weight |
431.45
|
| Exact Mass |
431.182
|
| CAS # |
862309-06-6
|
| PubChem CID |
11697697
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.515
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
31
|
| Complexity |
655
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=NC2=CC=CC(=C2C(=O)N1C3=CC=C(C=C3)OCCCN4CCCC4)C(F)(F)F
|
| InChi Key |
DDDZBLNULGDPGA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H24F3N3O2/c1-16-27-20-7-4-6-19(23(24,25)26)21(20)22(30)29(16)17-8-10-18(11-9-17)31-15-5-14-28-12-2-3-13-28/h4,6-11H,2-3,5,12-15H2,1H3
|
| Chemical Name |
2-methyl-3-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-5-(trifluoromethyl)quinazolin-4-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 50 mg/mL (115.89 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.90 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 12.5 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: ≥ 1.25 mg/mL (2.90 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 12.5 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: ≥ 1.25 mg/mL (2.90 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 | 2.3178 mL | 11.5888 mL | 23.1777 mL | |
| 5 mM | 0.4636 mL | 2.3178 mL | 4.6355 mL | |
| 10 mM | 0.2318 mL | 1.1589 mL | 2.3178 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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