| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
Divalent metal transporter 1 (DMT1, also known as NRAMP2, SLC11A2, DCT1). DMT1 blocker 2 blocks DMT1-mediated ferrous iron uptake. The calcein assay IC50 for DMT1 inhibition is 1.53 μM. [1]
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|---|---|
| ln Vitro |
DMT1 blocker 2 (Compound 12f) does not cause any harm to HepG2 cells at 10 μM after 24 hours [1]. CYP3A4 activity is 44% inhibited by DMT1 blocker 2 (10 μM) [1].
DMT1 blocker 2 was evaluated in a calcein-AM fluorescence quenching assay using CHO cells expressing human DMT1B⁺IRE. The compound inhibited DMT1-mediated Fe²⁺ uptake with an IC50 of 1.53 μM. It showed no cytotoxicity in HepG2 cells (devoid of HepG2 cytotoxicity, exact values not reported). [1] |
| ln Vivo |
In an acute model of iron hyperabsorption, DMT1 blocker 2 (50 mg/kg; oral) inhibits the response of intestinal cells to iron-containing foods [1].
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| Cell Assay |
The calcein-AM assay was performed as follows: CHO cells transformed with human DMT1B⁺IRE were loaded with calcein-AM. Test compounds including DMT1 blocker 2 were incubated with the cells. Subsequently, ferrous sulfate was added to the medium. DMT1-mediated uptake of ferrous ion leads to formation of a calcein-Fe²⁺ chelate, quenching calcein fluorescence. In the presence of DMT1 blockers like DMT1 blocker 2, ferrous ion uptake and fluorescence quenching are attenuated. IC50 values were determined from no fewer than two replicate experiments. [1]
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| Animal Protocol |
Animal/Disease Models: Weanling (3-4 weeks) rats were placed on a low-iron diet for four weeks [1]
Doses: 50 mg/kg Route of Administration: po (oral gavage), followed by iron challenge 1 hour later Experimental Results: Attenuated post-challenge serum iron increase. |
| ADME/Pharmacokinetics |
- Solubility in phosphate-buffered saline (pH 7.4): 159 μg/mL. [1]
- Caco-2 permeability: A→B transport = 0.3 × 10⁻⁶ cm/s, B→A transport = 0.67 × 10⁻⁶ cm/s. [1] - CYP3A4 inhibition: 46% inhibition at 10 μM. [1] |
| References | |
| Additional Infomation |
DMT1 blocker 2 is the simplified analog derived from the HTS hit 1 (triazinone pyrazole). The three series of substituted pyrazoles (4-amido-5-hydroxypyrazoles, 4-aryl-5-hydroxypyrazoles, and tricyclic pyrazoles) were elaborated from this simplified structure. DMT1 blocker 2 served as a reference compound in SAR tables (Tables 1–4) for comparing potency and physicochemical properties. [1]
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| Molecular Formula |
C16H13N3O
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|---|---|
| Molecular Weight |
263.293923139572
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| Exact Mass |
263.105
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| CAS # |
1062648-63-8
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| PubChem CID |
25016113
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| Appearance |
White to yellow solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
20
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| Complexity |
445
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC2=C(C3=CC=CC=C31)C(=O)N(N2)C4=CC=CC=N4
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| InChi Key |
BKZBNMNLRQXSHY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13N3O/c20-16-15-12-6-2-1-5-11(12)8-9-13(15)18-19(16)14-7-3-4-10-17-14/h1-7,10,18H,8-9H2
|
| Chemical Name |
2-pyridin-2-yl-4,5-dihydro-3H-benzo[e]indazol-1-one
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~189.90 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.50 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.50 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 25.0 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 | 3.7981 mL | 18.9905 mL | 37.9809 mL | |
| 5 mM | 0.7596 mL | 3.7981 mL | 7.5962 mL | |
| 10 mM | 0.3798 mL | 1.8990 mL | 3.7981 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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