| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
NPD-001 targets Trypanosoma brucei phosphodiesterases TbrPDEB1 and TbrPDEB2. These enzymes are essential for the survival and proliferation of the parasite that causes African trypanosomiasis (sleeping sickness). NPD-001 also inhibits human PDE4, indicating some cross-species activity. Inhibition of TbrPDEB1/2 leads to increased cAMP levels in parasites.
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| ln Vitro |
In vitro, NPD-001 acts as a potent inhibitor of TbrPDEB1 and TbrPDEB2 with IC₅₀ values of 4 nM and 3 nM, respectively. It also inhibits hPDE4B1 with an IC₅₀ of 0.6 nM, making it 10-fold more potent on hPDE4 than on TbrPDEB1. The compound shows good antitrypanosomal activity with an IC₅₀ of 80 nM.
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| ln Vivo |
NPD-001 increases cAMP levels in parasites, prevents cytokinesis, and causes the parasites to form multinucleated, multi-flagellated cells that eventually lyse. Its in vivo activity has been demonstrated in animal models of Trypanosoma brucei infection. The compound can be used for the research of Trypanosoma infection.
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| Enzyme Assay |
The in vitro enzyme assay for NPD-001 involves measuring its inhibitory activity against TbrPDEB1 and TbrPDEB2 phosphodiesterases in cell-free systems. These assays use purified enzyme preparations and measure the hydrolysis of cyclic nucleotide substrates in the presence of the compound. Inhibitory potency is determined by assessing IC₅₀ values (4 nM for TbrPDEB1 and 3 nM for TbrPDEB2).
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| Cell Assay |
In vitro cellular assays for NPD-001 are performed using Trypanosoma brucei parasite cultures. These assays measure the compound's ability to inhibit parasite growth, with an IC₅₀ of 80 nM reported. The compound's effects on cAMP levels, cytokinesis, and parasite morphology are also assessed. These assays confirm its antitrypanosomal mechanism of action.
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| Animal Protocol |
In vivo animal studies for NPD-001 are conducted in mouse models of Trypanosoma brucei infection. These studies typically involve administration of the compound, followed by assessment of parasite clearance, survival, and disease progression. The compound's efficacy in reducing parasite burden and improving survival outcomes is evaluated in these models.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NPD-001 are characterized by its molecular properties: molecular formula C₃₃H₄₀N₆O₄ and molecular weight 584.72 g/mol. The compound has a predicted density of 1.32 g/cm³. Its pharmacokinetic profile supports its use in preclinical studies for the treatment of Trypanosoma infection.
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| Toxicity/Toxicokinetics |
Toxicology studies of NPD-001 have been conducted to support its development as an antitrypanosomal agent. These studies include assessments of cytotoxicity and selectivity for parasite versus host enzymes. As a phosphodiesterase inhibitor that also targets human PDE4, its toxicology profile includes potential effects on human PDE4-mediated functions.
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| References | |
| Additional Infomation |
NPD-001 (CAS: 469863-16-9) is a potent inhibitor of Trypanosoma brucei phosphodiesterases TbrPDEB1 and TbrPDEB2 with IC₅₀ values of 4 nM and 3 nM, respectively. It also inhibits hPDE4B1 with an IC₅₀ of 0.6 nM. The compound has a molecular formula of C₃₃H₄₀N₆O₄ and a molecular weight of 584.72 g/mol. It is used for research of Trypanosoma infection.
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| Molecular Formula |
C33H40N6O4
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|---|---|
| Molecular Weight |
584.708507537842
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| Exact Mass |
584.311
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| CAS # |
469863-16-9
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| PubChem CID |
71719394
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| Appearance |
White to off-white solid powder
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| LogP |
6.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
43
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| Complexity |
948
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1(=O)[C@]2([H])[C@@]([H])(CC=CC2)C(C2=CC=C(OC)C(OCCCCOC3=CC=C(C4=NNN=N4)C=C3)=C2)=NN1C1CCCCCC1
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| InChi Key |
DNDNLFXKQSTINI-WUFINQPMSA-N
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| InChi Code |
InChI=1S/C33H40N6O4/c1-41-29-19-16-24(31-27-12-6-7-13-28(27)33(40)39(36-31)25-10-4-2-3-5-11-25)22-30(29)43-21-9-8-20-42-26-17-14-23(15-18-26)32-34-37-38-35-32/h6-7,14-19,22,25,27-28H,2-5,8-13,20-21H2,1H3,(H,34,35,37,38)/t27-,28+/m0/s1
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| Chemical Name |
(4aS,8aR)-2-cycloheptyl-4-[4-methoxy-3-[4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy]phenyl]-4a,5,8,8a-tetrahydrophthalazin-1-one
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| Synonyms |
NPD001; NPD 001; NPD-001
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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 : ~100 mg/mL (~171.02 mM)
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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 | 1.7102 mL | 8.5512 mL | 17.1025 mL | |
| 5 mM | 0.3420 mL | 1.7102 mL | 3.4205 mL | |
| 10 mM | 0.1710 mL | 0.8551 mL | 1.7102 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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