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25mg | ||
50mg | ||
100mg | ||
250mg |
Melphalan flufenamide (J1; J-1; Prodrug J-1; Melflufen; Pepaxto) is a potent and dipeptide-based melphalan prodrug acting as an alkylating agent with potential anticancer and anti-angiogenic activities. It was approved in 2021 to treat relapsed or refractory multiple myeloma. Melphalan flufenamide alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages.
ln Vitro |
The viability of MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, ARP-1, and ANBL-6 cells is lowered in a concentration-dependent manner by melflufen (melphalan flufenamide) (0.5-10 μM; 24 hours)[1]. In MM.1S cells, melflufen causes apoptosis [1]. Additionally, melphalan is a strong exosome secretion activator [3].
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ln Vivo |
In a xenograft mouse model, melflufen (3 mg/kg; intravenously administered twice weekly for two weeks) exhibits anti-MM action [1].
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Cell Assay |
Cell viability assay
Cell Types: Multiple myeloma cells: MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, ARP-1, ANBL-6 Cell Tested Concentrations: 0.5, 1, 3, 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: A significant concentration-dependent decrease in viability was observed for all cell lines. |
Animal Protocol |
Animal/Disease Models: CB-17 SCID mouse (human plasmacytoma MM.1S xenograft mouse model) [1]
Doses: 3 mg/kg Route of Administration: intravenous (iv) (iv)injection; twice a week for two weeks Experimental Results: Significant Dramatically inhibits MM tumor growth and prolongs mouse survival. |
References |
[1]. Chauhan D, et al. In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells. Clin Cancer Res. 2013;19(11):3019-3031.
[2]. Ray A, et al. A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells. Br J Haematol. 2016;174(3):397-409. [3]. McAndrews KM, et, al. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019 Mar 30;18(1):52. |
Molecular Formula |
C24H30CL2FN3O3
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Molecular Weight |
498.4204
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CAS # |
380449-51-4
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Related CAS # |
Melflufen hydrochloride;380449-54-7
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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Synonyms |
J1 J-1 Prodrug J-1 MelflufenPepaxto
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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) |
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
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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 | 2.0063 mL | 10.0317 mL | 20.0634 mL | |
5 mM | 0.4013 mL | 2.0063 mL | 4.0127 mL | |
10 mM | 0.2006 mL | 1.0032 mL | 2.0063 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.