MK-0249
Based on 1 publication(s) in Google Scholar
MK-0249 (Compound 1) is a potent, selective and orally active histamine H3 receptor antagonist, with an IC50 of 1.7 nM for human H3.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 98.28%
- CAS No.: 862309-06-6
- Formule: C23H24F3N3O2
- Masse moléculaire:431.45
-
Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Activité biologique
-
Chemical Information
-
Solvant et solubilité
- Pureté et documentation
- Références
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) MK-0249
MoreVoir tous les produits spécifiques à Isoform Histamine Receptor
More
Activité biologique
Description
IC50 & Target
|
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) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| CHO-K1 | IC50 |
1.7 nM
Compound: 1
|
Inverse agonist activity at human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition of N-alpha-methylhistamine-induced [35S]GTPgammaS binding
Inverse agonist activity at human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition of N-alpha-methylhistamine-induced [35S]GTPgammaS binding
|
[PMID: 18598020] |
| HEK293 | IC50 |
>10 μM
Compound: 1
|
Displacement of [35S]N-[(4R)-1'-[(2R)-6-cyano-1,2,3,4-tetrahydro-2-naphthalenyl]-3,4-dihydro-4-hydroxyspiro[2H-1-benzopyran-2,4'-piperidin]-6-yl]methanesulfonamide from human ERG in HEK293 cells
Displacement of [35S]N-[(4R)-1'-[(2R)-6-cyano-1,2,3,4-tetrahydro-2-naphthalenyl]-3,4-dihydro-4-hydroxyspiro[2H-1-benzopyran-2,4'-piperidin]-6-yl]methanesulfonamide from human ERG in HEK293 cells
|
[PMID: 18598020] |
In Vitro
MK-0249 (Compound 1) shows very good hepatic clearance values (CLh e 11 mL/min/kg), and is a substrate for rat P-gp but not for human P-gp[1].
MK-0249 displays potent binding affinity to human, rat, and rhesus H3 receptors with Ki values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively[1].
MK-0249 shows high intrinsic activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value in mdr1a (-/-) mice than in mdr1a (+/+) mice[1].
MK-0249 shows rodent brain permeability and is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:SD rats[1]
-
Dosage:3, 10 and 30 mg/kg
-
Administration:Oral administration, once
-
Result:Showed a statistically significant increase in tele-methylhistamine levels at 30 mg/kg.
-
Animal Model:P-gp-deficient mdr1a (-/-) and wild type mdr1a (+/+) CF-1 mice[1]
-
Dosage:10 mg/kg
-
Administration:Oral administration, once
-
Result:The brain-to-plasma ratio in mdr1a (-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) and mdr1a (+/+) mice (b/p = 0.8).
-
Animal Model:Male Sprague-Dawley rats, male Beagle dogs, and male rhesus monkeys[1]
-
Dosage:1 or 3 mg/kg
-
Administration:IV or PO (Pharmacokinetic Analysis)
-
Result:Pharmacokinetic Parameters of 1 in Rats, Dogs, and Rhesus Monkeysa[1]
iv (1 mg/kg) po (3 mg/kg) CLp
(mL/min/kg)Vdss
(L/kg)t1/2
(h)Cmax
(µM)AUC0-∞
(µM h)Fb
(%)rat 12 4.4 5.5 1.01 6.35 65 dog 19 9.7 9.9 1.8 11.8 >100 --> Essai clinique
NCT Number Sponsor Condition Start Date Phase
NCT01329991 Plexxikon| 2011-05 PHASE1 
Chemical Information
-
CAS No. 862309-06-6
-
Appearance Solid
-
Masse moléculaire 431.45
-
Formule C23H24F3N3O2
-
Color Light yellow to yellow
-
SMILES
O=C1N(C2=CC=C(OCCCN3CCCC3)C=C2)C(C)=NC4=C1C(C(F)(F)F)=CC=C4
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (1)
AllJournal Impact Factor-
Journal Impact Factor
-
Most Recent
Solvant et solubilité
In Vitro:
DMSO : 50 mg/mL (115.89 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
View the Complete Stock Solution Preparation TablePreparing Stock SolutionsView the Complete Stock Solution Preparation TableConcentration Solvent Mass1 mg5 mg10 mgConcentrationSolventMass1 mM2.3178 mL11.5888 mL23.1777 mL5 mM0.4636 mL2.3178 mL4.6355 mL10 mM0.2318 mL1.1589 mL2.3178 mLPlease 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.
Calculateur de molaritéMass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)= × ×Calculateur de dilutionConcentration (start) × Volume (start) = Concentration (final) × Volume (final)
×=×In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
Stock Solution Working Solution- 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
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).
Working solution concentration: 0.22 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 contactMethod for preparing in vivo working solution for animal experiments:
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μLSaline .Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solutionIf 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.
Pureté et documentation
Select Batch:Pureté: 99.98%Assay: 99.98%ee.: 99.98%-
Fiche technique (277 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
Instruction de manipulation (2659 KB)
Références
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.
Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg DMSO 1 mM 2.3178 mL 11.5888 mL 23.1777 mL 57.9441 mL 5 mM 0.4636 mL 2.3178 mL 4.6355 mL 11.5888 mL 10 mM 0.2318 mL 1.1589 mL 2.3178 mL 5.7944 mL 15 mM 0.1545 mL 0.7726 mL 1.5452 mL 3.8629 mL 20 mM 0.1159 mL 0.5794 mL 1.1589 mL 2.8972 mL 25 mM 0.0927 mL 0.4636 mL 0.9271 mL 2.3178 mL 30 mM 0.0773 mL 0.3863 mL 0.7726 mL 1.9315 mL 40 mM 0.0579 mL 0.2897 mL 0.5794 mL 1.4486 mL 50 mM 0.0464 mL 0.2318 mL 0.4636 mL 1.1589 mL 60 mM 0.0386 mL 0.1931 mL 0.3863 mL 0.9657 mL 80 mM 0.0290 mL 0.1449 mL 0.2897 mL 0.7243 mL 100 mM 0.0232 mL 0.1159 mL 0.2318 mL 0.5794 mL 
MK-0249 Related Classifications
HY-U00076 Related Classifications
Assay Types -
Powered by Bioz