| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
ISPA-28 specifically targets the plasmodial surface anion channel (PSAC), a nutrient uptake channel on the surface of Plasmodium falciparum-infected red blood cells. It binds directly and reversibly to CLAG3 (cytoadherence-linked asexual protein 3), a critical component of the PSAC, thereby blocking channel activity and parasite nutrient acquisition.
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| ln Vitro |
Only Dd2 channels (K0.5 values of 56 nM and 43 μM for Dd2 and HB3 channels, respectively) are effectively inhibited by ISPA-28[2].
In vitro, ISPA-28 (0.01-100 uM) inhibits PSAC channel activity in P. falciparum-infected red blood cells with K0.5 values of 56 nM for Dd2 channels and 43 uM for HB3 channels, demonstrating strain-specific potency. It blocks parasite growth in culture at low micromolar concentrations. The compound is specific for PSAC and does not affect host ion channels. |
| Enzyme Assay |
For non-cellular CLAG3 binding, recombinant CLAG3 protein is expressed in a cell-free system or in HEK-293 cells. Binding of ISPA-28 to CLAG3 is assessed by surface plasmon resonance (SPR) or microscale thermophoresis (MST). For SPR, biotinylated CLAG3 is immobilized on a streptavidin sensor chip, and ISPA-28 (0.1-100 uM) is injected to determine kinetic parameters. Alternatively, saturation binding assays using radiolabeled [3H]-ISPA-28 are performed.
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| Cell Assay |
For cell-based PSAC inhibition, P. falciparum-infected human red blood cells (RBCs, 5-10% parasitemia) are suspended in buffer containing a fluorescent or radiolabeled substrate (e.g., [3H]sorbitol, [14C]alanine, or a fluorescent chloride-sensitive dye). ISPA-28 (0.001-100 uM) is added, and substrate uptake is measured after 10-30 minutes. Parasite growth inhibition (IC50) is measured by 48-hour SYBR Green fluorescence assay.
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| Animal Protocol |
For in vivo evaluation, P. falciparum-infected SCID mice with engrafted human RBCs (SCID-hu mice) or P. berghei (rodent parasite) expressing PSAC are used. Mice are treated with ISPA-28 (5-50 mg/kg, oral or intraperitoneal) once or twice daily for 4-7 days. Parasitemia is monitored by Giemsa-stained blood smears or by luciferase imaging for luciferase-expressing parasites. Survival is recorded.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for ISPA-28 are not available. As a small molecule (MW 408.45, C21H24N6O3), it is expected to have moderate oral bioavailability. No detailed PK parameters are publicly available.
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| Toxicity/Toxicokinetics |
Toxicity data for ISPA-28 are limited. In preclinical studies, the compound appears to be well tolerated at effective doses, with no significant weight loss or behavioral changes reported. As a PSAC antagonist, ISPA-28 is expected to be selective for parasite channels over host channels, suggesting a favorable safety margin.
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| References |
[1]. Sanjay A Desai, et al. Ion and Nutrient Uptake by Malaria Parasite-Infected Erythrocytes.
[2]. Wang Nguitragool, et al. Proteolysis at a Specific Extracellular Residue Implicates Integral Membrane CLAG3 in Malaria Parasite Nutrient Channels. |
| Additional Infomation |
ISPA-28 is a research-grade tool for studying PSAC function and for antimalarial drug discovery. It has been used to validate CLAG3 as a drug target. The compound shows strain-specific potency (Dd2 > HB3), which may be due to polymorphisms in CLAG3. No clinical trials are registered for ISPA-28.
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| Molecular Formula |
C21H24N6O3
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|---|---|
| Molecular Weight |
408.45
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| Exact Mass |
408.19
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| CAS # |
1006335-39-2
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| PubChem CID |
17095977
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.672
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| LogP |
0.18
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
760
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1N=C(C)C(C2=NOC(C(NC3=C(C)N(C)N(C4=CC=CC=C4)C3=O)=O)C2)=C1
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| InChi Key |
YMLINDVVJXDIRW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24N6O3/c1-5-26-12-16(13(2)23-26)17-11-18(30-24-17)20(28)22-19-14(3)25(4)27(21(19)29)15-9-7-6-8-10-15/h6-10,12,18H,5,11H2,1-4H3,(H,22,28)
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| Chemical Name |
N-(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-3-(1-ethyl-3-methylpyrazol-4-yl)-4,5-dihydro-1,2-oxazole-5-carboxamide
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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 (244.83 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 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 25.0 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: ≥ 2.5 mg/mL (6.12 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4483 mL | 12.2414 mL | 24.4828 mL | |
| 5 mM | 0.4897 mL | 2.4483 mL | 4.8966 mL | |
| 10 mM | 0.2448 mL | 1.2241 mL | 2.4483 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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