| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
Plasmodium falciparum hemozoin formation. Like its parent drug lumefantrine, Desbutyl Lumefantrine is an aryl amino alcohol compound that exerts its antimalarial effect by interfering with the detoxification pathway of heme. When P. falciparum digests hemoglobin, it releases toxic heme. DBL inhibits the polymerization of heme into non-toxic hemozoin crystals, causing the accumulation of toxic heme, resulting in parasite membrane damage and ultimately parasite death.
|
|---|---|
| ln Vitro |
Desbutyl Lumefantrine demonstrates potent in vitro antimalarial activity against P. falciparum. Against both chloroquine-sensitive (3D7) and chloroquine-resistant (W2mef) strains, DBL exhibits IC₅0 values of 9.0 nM and 9.5 nM, respectively. Notably, these IC₅0 values indicate that DBL is at least 3 times more potent than its parent drug, lumefantrine (IC₅0 ~55-65 nM), confirming that DBL is a major contributor to the therapeutic effect observed in patients. [8L17-L18]
|
| ln Vivo |
In vivo, Desbutyl Lumefantrine is the primary long-acting agent in artemether-lumefantrine therapy. While artemether rapidly clears the bulk of parasites, DBL contributes to the prolonged post-treatment prophylactic effect and eliminates residual parasites. The in vivo concentration of DBL is directly correlated with treatment outcome and prevention of recrudescence, highlighting its critical pharmacokinetic-pharmacodynamic role.
|
| Enzyme Assay |
Dedicated non-cell-based assays for DBL are limited. The antimalarial activity of DBL can be assessed using a cell-free beta-hematin (hemozoin) inhibition assay. A 96-well plate is prepared with 50 uL of varying concentrations of DBL in a heme polymerization buffer, then 50 uL of hemin solution is added, and the reaction is initiated by adding acetic acid to reduce the pH to 5.0. After incubation, the amount of beta-hematin formed is quantified by measuring absorbance at 405 nm.
|
| Cell Assay |
P. falciparum (3D7 or W2mef) cultures are synchronized to the ring stage. Parasitized red blood cells (2% parasitemia, 2% hematocrit) are seeded in 96-well plates. Serial dilutions of Desbutyl Lumefantrine (0.01-1000 nM) are added. Plates are incubated for 48-72 hours in a gas mixture. After incubation, [3H]hypoxanthine (1 microCi/well) is added, and the plates are incubated for an additional 18-24 hours. Cells are harvested, and the incorporated radioactivity is measured.
|
| Animal Protocol |
A murine model of P. berghei infection is used. Female Swiss Webster mice are infected intraperitoneally with P. berghei ANKA-infected erythrocytes. Mice are then randomized and treatment is administered via oral gavage once daily for 4 days (standard Peters‘ 4-day test). Desbutyl Lumefantrine is dosed (e.g., 1-10 mg/kg) in a suitable vehicle (e.g., Tween-80/water). Parasitemia is assessed on day 4 post-infection via thin blood smears stained with Giemsa. Percent suppression is calculated.
|
| ADME/Pharmacokinetics |
DBL is primarily a research metabolite and not a clinical drug. Pharmacokinetic data is derived from patients taking lumefantrine. DBL has a longer elimination half-life (t1/2) than lumefantrine, ranging from 4-6 days in humans, explaining its prolonged prophylactic effect after treatment. It is highly protein-bound (>99.9%). It is a CYP3A4 metabolite, and its concentration is impacted by co-medications that induce or inhibit this enzyme. The molecular weight is 472.8 g/mol.
|
| Toxicity/Toxicokinetics |
Desbutyl Lumefantrine has been shown to inhibit the human ether-a-go-go (hERG) potassium channel (Kv11.1), with an IC₅0 of 5.49 uM in HEK293 cells, suggesting a risk of QT prolongation at very high concentrations. No data on acute or chronic toxicity specific to DBL alone is available, but it shares the general safety profile of arylamino alcohols with potential for phospholipidosis or hepatotoxicity at extreme overdoses.
|
| Additional Infomation |
Desbutyl Lumefantrine is a pharmacopoeial impurity standard and an active metabolite, not an approved drug for monotherapy. It is a critical standard for therapeutic drug monitoring (TDM) of lumefantrine treatments and is used to study artemether-lumefantrine resistance, as reduced susceptibility to DBL is a common resistance mechanism in P. falciparum. It is also used in neuropsychopharmacology research for its hERG channel blocking properties. [8L10-L12]
|
| Molecular Formula |
C26H24NOCL3
|
|---|---|
| Molecular Weight |
472.83386
|
| Exact Mass |
471.092
|
| CAS # |
355841-11-1
|
| Related CAS # |
Desbutyl Lumefantrine-d9;1346606-35-6
|
| PubChem CID |
9934522
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
626.8±55.0 °C at 760 mmHg
|
| Flash Point |
332.9±31.5 °C
|
| Vapour Pressure |
0.0±1.9 mmHg at 25°C
|
| Index of Refraction |
1.661
|
| LogP |
9.09
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
31
|
| Complexity |
606
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCCCNCC(C1=CC(=CC/2=C1C3=C(C=C(C=C3)Cl)\C2=C\C4=CC=C(C=C4)Cl)Cl)O
|
| InChi Key |
YLBUTQNEBVPTES-NHDPSOOVSA-N
|
| InChi Code |
InChI=1S/C26H24Cl3NO/c1-2-3-10-30-15-25(31)24-14-19(29)13-23-21(11-16-4-6-17(27)7-5-16)22-12-18(28)8-9-20(22)26(23)24/h4-9,11-14,25,30-31H,2-3,10,15H2,1H3/b21-11-
|
| Chemical Name |
2-(butylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]fluoren-4-yl]ethanol
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1149 mL | 10.5746 mL | 21.1493 mL | |
| 5 mM | 0.4230 mL | 2.1149 mL | 4.2299 mL | |
| 10 mM | 0.2115 mL | 1.0575 mL | 2.1149 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
