| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
DSM265 targets Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway of the malaria parasite. It exhibits an IC50 of 8.9 nM against PfDHODH and displays excellent selectivity versus human DHODH.
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| ln Vitro |
In vitro, DSM265 potently inhibits PfDHODH with an IC50 of 8.9 nM. It also inhibits the growth of Pf3D7 parasites with an EC50 of 4.3 nM. Its selectivity for the parasite enzyme over the human enzyme is a key feature of its antimalarial activity.
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| ln Vivo |
Strong in vivo antimalarial activity is exhibited by DSM265 (0.5 to 75 mg/kg; oral; twice daily; for 4 days; NOD-scid IL-2Rγnull (NSG) mice), with a 90% effective dosage (ED90) of 3 mg/kg/next day (1.5 mg/kg twice day). The greatest rate of parasite death occurs at doses of 13 mg/kg per day (6.4 mg/kg twice daily) or higher. DSM265 has a 2-4 hour terminal elimination half-life (t1/2) in mice when taken orally at doses of 0.5 to 75 mg/kg [2].
In vivo, DSM265 is a long-acting antimalarial agent. Its oral bioavailability and long duration of action make it suitable for the treatment and prevention of malaria. |
| Enzyme Assay |
In vitro enzyme assays for DSM265 involve measuring the inhibition of purified PfDHODH activity. The enzyme is incubated with dihydroorotate and the cofactor (e.g., CoQ) in the presence of varying concentrations of the compound. The oxidation of dihydroorotate is measured spectrophotometrically to determine the IC50. Selectivity over human DHODH is confirmed using the same assay with the human enzyme.
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| Cell Assay |
In vitro cellular assays for DSM265 are performed using Plasmodium falciparum parasite cultures. Parasites are treated with the compound for 48-72 hours, and parasite growth is measured by assessing the incorporation of [³H]-hypoxanthine or by using a fluorescent dye (e.g., SYBR Green) to quantify DNA. The EC50 is determined from the inhibition curve.
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| Animal Protocol |
Animal/Disease Models: NOD-scid IL-2Rγnull (NSG) mice (23-36 g) [2]
Doses: 0.5 to 75 mg/kg Route of Administration: oral; Route of Administration: oral. twice (two times) daily; for 4 days Experimental Results: Potent antimalarial activity at a 90% effective dose (ED90) of 3 mg/kg daily (1.5 mg/kg twice (two times) daily). In vivo animal studies for DSM265 are conducted in mouse models of malaria, such as the Plasmodium berghei or P. falciparum-infected mouse models. The compound is administered orally, and parasitemia is measured over time to assess its antimalarial efficacy and duration of action. |
| ADME/Pharmacokinetics |
DSM265 is an orally bioavailable compound with a long duration of action. Its PK properties have been characterized in preclinical species and humans, supporting its development as an antimalarial agent. Its long half-life allows for once-daily or less frequent dosing.
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| Toxicity/Toxicokinetics |
Toxicological data for DSM265 are not detailed in publicly available sources. As a compound that has entered clinical trials, it would have undergone standard preclinical safety assessments. Its safety profile would be evaluated in the context of its use as an antimalarial.
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| References |
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| Additional Infomation |
DSM265 has been used in research trials for malaria prevention and treatment.
DSM265 is a PfDHODH inhibitor. It is being developed as a long-acting antimalarial for the treatment and prophylaxis of malaria. It has shown promise in clinical trials. |
| Molecular Formula |
C14H12F7N5S
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|---|---|
| Molecular Weight |
415.33
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| Exact Mass |
415.07
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| CAS # |
1282041-94-4
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| PubChem CID |
51347395
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| Appearance |
White to off-white solid powder
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| LogP |
3.76
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
566
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OIZSVTOIBNSVOS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H12F7N5S/c1-8-7-11(26-13(22-8)24-12(25-26)14(2,15)16)23-9-3-5-10(6-4-9)27(17,18,19,20)21/h3-7,23H,1-2H3
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| Chemical Name |
2-(1,1-difluoroethyl)-5-methyl-N-[4-(pentafluoro-λ6-sulfanyl)phenyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
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| Synonyms |
DSM 265; DSM-265; DSM265
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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 (~120.39 mM)
Ethanol : ~11.11 mg/mL (~26.75 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.62 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 27.5 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: ≥ 2.75 mg/mL (6.62 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 27.5 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 | 2.4077 mL | 12.0386 mL | 24.0772 mL | |
| 5 mM | 0.4815 mL | 2.4077 mL | 4.8154 mL | |
| 10 mM | 0.2408 mL | 1.2039 mL | 2.4077 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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