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Metoprine

Cat No.:V10640 Purity: ≥98%
Metoprine (BW 197U) is a potent inhibitor of histamine N-methyltransferase (HMT).
Metoprine
Metoprine Chemical Structure CAS No.: 7761-45-7
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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10mg
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Product Description
Metoprine (BW 197U) is a potent inhibitor of histamine N-methyltransferase (HMT). Metoprine is a diaminopyrimidine analogue that can cross the BBB (blood-brain barrier) and increase brain histamine levels by inhibiting HMT. Metoprine is an antifolate and anticancer drug.
Biological Activity I Assay Protocols (From Reference)
ln Vivo
Metropine (BW 197U; 2-10 mg/kg; IP) improves memory deficits produced by magnocellular nucleus basalis (NBM) injury in a dose-dependent manner [2]. Intraperitoneal metropine injection generates a number of behavioral effects, including reduced meal intake and increased water consumption [1].
Animal Protocol
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (200-280g) [2]
Doses: 2, 5, 10 mg/kg
Route of Administration: IP
Experimental Results: Improvement in a dose-dependent manner by the magnocellular nucleus basalis ( NBM) injury-induced memory deficits, the metastasis latency was Dramatically prolonged at the high dose of 10 mg/kg.
References

[1]. Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose. Drug Target Insights. 2016 Mar 2;10:1-7.

[2]. Effects of brain histamine on memory deficit induced by nucleus basalis-lesion in rats. Acta Pharmacol Sin. 2002 Jan;23(1):66-70.

[3]. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs. J Mol Biol. 2005 Oct 21;353(2):334-344.

Additional Infomation
Metoprine is a diaminopyrimidine folate antagonist with potential antineoplastic activity. Metoprine inhibits dihydrofolate reductase, resulting in decreased cellular folate metabolism and cell growth; it also inhibits histamine-N-methyltransferase, resulting in decreased histamine catabolism. Lipid-soluble metoprine is capable of crossing the blood-brain barrier. (NCI04)
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C11H10N4CL2
Molecular Weight
269.1299
Exact Mass
268.028
CAS #
7761-45-7
PubChem CID
24466
Appearance
White to light yellow solid powder
Density
1.447g/cm3
Boiling Point
483.7ºC at 760 mmHg
Melting Point
275-276ºC
Flash Point
246.3ºC
Index of Refraction
1.678
LogP
4.085
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
1
Heavy Atom Count
17
Complexity
266
Defined Atom Stereocenter Count
0
InChi Key
VQJHOPSWBGJHQS-UHFFFAOYSA-N
InChi Code
InChI=1S/C11H10Cl2N4/c1-5-9(10(14)17-11(15)16-5)6-2-3-7(12)8(13)4-6/h2-4H,1H3,(H4,14,15,16,17)
Chemical Name
5-(3,4-dichlorophenyl)-6-methylpyrimidine-2,4-diamine
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 Data
Solubility (In Vitro)
DMSO : ~20.83 mg/mL (~77.40 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.73 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 20.8 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: ≥ 2.08 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.7157 mL 18.5784 mL 37.1568 mL
5 mM 0.7431 mL 3.7157 mL 7.4314 mL
10 mM 0.3716 mL 1.8578 mL 3.7157 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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Interactions of HNMT and diphenhydramine. (a) Chemical structure of diphenhydramine (top panel). The simulated-annealing omit electron density map is contoured at 3.5σ above the mean (bottom panel). (b) Ribbon diagram of HNMT-diphenhydramine-AdoHcy. The N terminus is in blue and the C terminus in red. (c) Active site pocket of HNMT reconstituted from the four structures. Residues adopting different rotomer conformation or disordered are labeled in white letter against red background. The side-chains of Glu246 and Tyr15 are disordered in the complex with diphenhydramine; the side-chain of Phe9 is disordered in the complexes with amodiaquine and metoprine, and adopts one rotamer in diphenhydramine and a different one in tacrine. (d) Detailed plot of HNMT–diphenhydramine interactions. The nitrogen atoms are in blue and the oxygen atoms in red. The carbon atoms are in cyan (HNMT) and in green (inhibitor). The broken lines indicate hydrogen bonds, whose distances are indicated (in Å).[3]. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs. J Mol Biol. 2005 Oct 21;353(2):334-344.
  • Interactions of HNMT–metoprine. (a) Chemical structure of metoprine (top panel). Lineweaver–Burke plot (bottom panel). The slope of each linear fit was plotted against the concentration of inhibitor and the intercept on the x-axis gave an estimate of Ki (91 nM). (b) Detailed plot of HNMT–diphenhydramine interactions. Replacing the chlorine atom (CL14) in the dichlorophenyl ring with sulfur might improve its interaction with Cys196 (indicated by a double-ended arrow). The simulated-annealing omit electron density map is contoured at 3.5σ above the mean (bottom panel).[3]. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs. J Mol Biol. 2005 Oct 21;353(2):334-344.
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