MK-0249 

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^[1].

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 K_i 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.

MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner^[1].
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 Clinical Trial Molecular Weight 431.45 Formula C23H24F3N3O2 CAS No. 862309-06-6 Appearance Solid Color Light yellow to yellow SMILES O=C1N(C2=CC=C(OCCCN3CCCC3)C=C2)C(C)=NC4=C1C(C(F)(F)F)=CC=C4 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 : 50 mg/mL (115.89 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 2.3178 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 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. Molarity Calculator Dilution Calculator Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol) Mass kg g mg μg ng pg = Concentration M mM μM nM pM × Volume L mL μL × Molecular Weight * Concentration (start) × Volume (start) = Concentration (final) × Volume (final) This equation is commonly abbreviated as: C1V1 = C2V2 Concentration (start) M mM μM nM pM C1 × Volume (start) L mL μL V1 = Concentration (final) M mM μM nM pM C2 × Volume (final) L mL μL V2 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: ≥ 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. Protocol 2 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. Protocol 3 Add each solvent one by one:  10% DMSO    90% Corn Oil Solubility: ≥ 1.25 mg/mL (2.90 mM); Clear solution This protocol yields a clear solution of ≥ 1.25 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 (12.5 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) g 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). Tel: 609-228-6898 E-mail: [email protected] Technical Support: [email protected] 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. Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution  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: 99.53% Select Batch: HY-U00076-55407 HY-U00076-89564 HY-U00076-113323 Data Sheet (277 KB) SDS (251 KB) COA (246 KB) HNMR (382 KB) LCMS (129 KB) Handling Instructions (2659 KB) References [1]. Nagase T, et al. Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem. 2008 Aug 14;51(15):4780-9.  [Content Brief] [1]. Nagase T, et al. Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem. 2008 Aug 14;51(15):4780-9. 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 Rating Lot Number * Submit an Image No file chosen (Maximum size is: 1024 Kb) PubMed ID If you have published this work, please enter the PubMed ID. Show My Name Your name will appear on the site. Email Remarks MK-0249 Related Classifications GPCR/G Protein Neuronal Signaling Immunology/Inflammation Histamine Receptor 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: MK-0249862309-06-6MK0249MK 0249Histamine ReceptorCNS dysfunctionInhibitorinhibitorinhibit Your Recently Viewed Products: Inquiry Online Your information is safe with us. * Required Fields. Product Name   Salutation Dr. Prof. Mr. Ms. Mrs. Miss. 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Product Name   Lot # Applicant Name *   Email Address * Phone Number   Department * Organization Name *   Country or Region * United StatesCanadaUnited KingdomAustraliaChinaGermanyFranceJapanKorea SouthSwitzerland------------------------------AlbaniaAlgeriaArgentinaArmeniaAustraliaAustriaAzerbaijanBahrainBangladeshBarbadosBelarusBelgiumBoliviaBosnia HerzegovinaBrazilBulgariaCameroonCanadaChileChinaColombiaCroatiaCyprusCzech RepublicDenmarkEcuadorEgyptEstoniaFijiFinlandFranceGeorgiaGermanyGibraltarGreeceHong Kong, ChinaHungaryIcelandIndiaIndonesiaIranIraqIrelandIsraelItalyJapanJordanKazakhstanKenyaKorea SouthKuwaitLatviaLebanonLibyaLithuaniaLuxembourgMacedoniaMalaysiaMaltaMexicoMoldovaMonacoMongoliaMontenegroMoroccoNepalNetherlandsNew ZealandNigeriaNorwayOmanPakistanParaguayPeruPhilippinesPolandPortugalPuerto RicoQatarRepublic of BeninRomaniaRussiaSaudi ArabiaSerbiaSingaporeSlovakiaSloveniaSouth AfricaSpainSri LankaSurinameSwedenSwitzerlandSyriaTaiwan, ChinaThailandTunisiaTurkeyUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVenezuelaVietnamZambiaZimbabweOther CountriesMacao, China Remarks Request for HNMR Report We have received your request and will respond to you as soon as possible. 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