| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Cryptosporidium phosphatidylinositol 4-kinase (CpPI4K / PI4K). CpPI4K is a lipid kinase essential for the survival and replication of Cryptosporidium parasites. KDU731 is an ATP-competitive inhibitor of CpPI4K with an enzymatic IC50 of 25 nM. Inhibition of CpPI4K disrupts parasite lipid metabolism and leads to parasite death.
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| ln Vitro |
In vitro, KDU731 demonstrates potent inhibition of Cryptosporidium infection with an IC50 of 25 nM. The compound blocks parasite replication in cell culture models of Cryptosporidium infection. Its potent activity and selectivity for parasite PI4K over host enzymes contribute to its favorable in vitro profile.
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| ln Vivo |
In immunocompromised IFN-γ KO mice, KDU731 (oral; 7 or 10 mg/kg; 16 days) exhibits strong anti-Cryptosporidium action and dramatically lowers oocyst shedding [2]. KDU731 (oral; 5 mg/kg; every 12 hours for 7 days) was well tolerated by all calves, and compared to vehicle-treated calves, treated calves ejected noticeably less oocysts from their stools [2].
In vivo, KDU731 exhibits strong anti-Cryptosporidium action in immunocompromised IFN-γ KO mice, dramatically lowering oocyst shedding at oral doses of 7 or 10 mg/kg for 16 days. The compound is orally bioactive and has a broad safety profile. Its efficacy in animal models supports its potential as a therapeutic agent for cryptosporidiosis, a major cause of diarrhea in immunocompromised patients and children in developing countries. |
| Enzyme Assay |
Cell-free enzyme assays for KDU731 use recombinant Cryptosporidium PI4K (CpPI4K) and a lipid substrate (phosphatidylinositol) in the presence of ATP. The compound is incubated with the enzyme at varying concentrations (0.001-10000 nM) for 30-60 minutes at room temperature. PI4K activity is measured by detecting the production of phosphatidylinositol-4-phosphate (PI4P) using a competitive ELISA or radiometric assay. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing the compound against host PI4K isoforms and other lipid kinases.
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| Cell Assay |
Cellular anti-Cryptosporidium assays are performed using HCT-8 or other intestinal epithelial cell lines infected with Cryptosporidium parvum oocysts. Cells are seeded in 24-well plates and infected with oocysts for 2-4 hours, then treated with KDU731 at concentrations ranging from 0.01-1000 nM for 48-72 hours. Parasite growth is quantified by measuring parasite DNA by qPCR, by immunofluorescence staining of parasite antigens, or by measuring oocyst output. IC50 values are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: 6-8 weeks old C57BL/6 IFN-γ knockout mice, containing 10,000 oocysts [1]
Doses: 7 or 10 mg/kg Route of Administration: po (po (oral gavage)) 7 or 10 mg/kg; 16 day Experimental Results: oocyst shedding Dramatically diminished. Animal/Disease Models: Newborn calves with 5 Sac shedding is Dramatically diminished. In vivo efficacy studies are conducted in immunocompromised mouse models of cryptosporidiosis, such as IFN-γ knockout mice or SCID mice. Mice are infected with C. parvum oocysts and treated with KDU731 orally at doses typically ranging from 1-30 mg/kg, once or twice daily for 7-16 days. Parasite burden is assessed by measuring oocyst shedding in feces by qPCR or microscopy. Intestinal parasite load is quantified at study termination by histopathology or qPCR of intestinal tissue. Weight loss, diarrhea severity, and survival are monitored. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of KDU731 demonstrate that the compound is orally bioavailable. PK parameters such as Cmax, Tmax, AUC, half-life, and oral bioavailability are determined in preclinical species. The compound's distribution to the gastrointestinal tract, the site of Cryptosporidium infection, is of particular interest. Metabolic stability is assessed using liver microsome or hepatocyte incubation studies. The compound's favorable PK properties support oral dosing for cryptosporidiosis treatment.
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| Toxicity/Toxicokinetics |
Toxicology studies of KDU731 indicate that the compound has a broad safety profile. As a CpPI4K inhibitor with selectivity for the parasite enzyme over host PI4Ks, the compound is expected to have a favorable safety margin. Standard toxicology studies (acute, subchronic, and chronic) in rodents and other species would be required for clinical development. At research-grade doses used in animal models, the compound is generally well-tolerated.
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| References | |
| Additional Infomation |
KDU731 is a research compound being developed for the treatment of cryptosporidiosis, a diarrheal disease caused by Cryptosporidium parasites. It represents a promising therapeutic candidate due to its potent activity, oral bioavailability, and broad safety profile. The compound has been evaluated in preclinical models and is a candidate for further development. It is available from chemical suppliers for research purposes only. Its mechanism as a selective CpPI4K inhibitor makes it a valuable tool for studying Cryptosporidium biology and developing anti-parasitic therapies.
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| Molecular Formula |
C22H16N6O2
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|---|---|
| Molecular Weight |
396.401443481445
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| Exact Mass |
396.133
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| CAS # |
1610610-48-4
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| PubChem CID |
76281701
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
697
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CN2C(C=1)=C(C=N2)C1C=CC(C(N)=O)=CC=1)N(C)C1C=CC(C#N)=CN=1
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| InChi Key |
YTIYJNWWLQSAAU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16N6O2/c1-27(20-7-2-14(11-23)12-25-20)22(30)17-8-9-28-19(10-17)18(13-26-28)15-3-5-16(6-4-15)21(24)29/h2-10,12-13H,1H3,(H2,24,29)
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| Chemical Name |
3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide
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| Synonyms |
KDU731; KDU-731; KDU 731
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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 : ~83.33 mg/mL (~210.22 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 | 2.5227 mL | 12.6135 mL | 25.2270 mL | |
| 5 mM | 0.5045 mL | 2.5227 mL | 5.0454 mL | |
| 10 mM | 0.2523 mL | 1.2614 mL | 2.5227 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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