| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
BKI-1369 targets Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1). As a bumped kinase inhibitor (BKI), it exploits the unique glycine gatekeeper residue in CDPK1 to achieve high selectivity, thereby minimizing off-target activity against mammalian kinases. The compound also inhibits the human Ether-à-go-go-related gene (hERG) potassium channel with an IC50 of 1.52 microM. Its activity against other apicomplexan parasites like Cryptosporidium parvum and Plasmodium falciparum indicates a potential for broader applications as an anti-parasitic drug.
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|---|---|
| ln Vitro |
In vitro, BKI-1369 potently inhibits TgCDPK1 with an IC50 value of 0.038 uM. The compound also increases hERG-inhibitory activity with an IC50 of 1.52 microM. In cell-based assays, BKI-1369 inhibits merozoite proliferation in intestinal porcine epithelial cells (IPEC-1) by at least 50% at a concentration of 40 nM, with nearly complete inhibition (>95%) observed at 200 nM. It shows antiproliferative activity against human CAPAN-1 cells with an IC50 >100 microM and against HCT-116 cells with an IC50 >55.2 microM.
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| ln Vivo |
In vivo, BKI-1369 has demonstrated efficacy in several animal models. A five-day oral treatment with BKI-1369 (10 mg/kg twice daily) effectively suppressed oocyst excretion and diarrhea, and improved body weight gain in piglets infected with Cystoisospora suis. The compound also reduces the parasite burden and disease severity in the gnotobiotic pig model. It has shown potency against Cryptosporidium parvum in infected mice and calves. Additionally, BKI-1369 has been reported to inhibit the growth of Toxoplasma gondii in vivo.
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| Enzyme Assay |
In vitro enzyme assays for BKI-1369 typically use recombinant TgCDPK1 enzyme to measure its inhibitory activity. The compound is incubated with the enzyme and a peptide substrate in the presence of ATP. The reaction is stopped, and the extent of phosphorylation is quantified, often using radiometric or fluorescence-based detection methods. IC50 values are calculated from concentration-response curves. For hERG inhibition, standard electrophysiological or radioligand binding assays are performed using cells expressing the hERG channel.
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| Cell Assay |
Cellular assays for BKI-1369 are performed using host cells infected with parasites such as Toxoplasma gondii or Cystoisospora suis. Infected cells, such as IPEC-1, are cultured in appropriate media and treated with varying concentrations of the compound. Parasite proliferation is assessed by quantifying parasite load, often using microscopy, qPCR, or by measuring the activity of parasite-expressed reporters. Host cell viability is concurrently assessed to determine the compound's selectivity and cytotoxicity.
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| Animal Protocol |
In vivo studies with BKI-1369 are conducted in animal models of parasitic infection, such as piglets infected with Cystoisospora suis. The compound is typically administered orally at defined doses (e.g., 10 mg/kg twice daily) and schedules. Efficacy is evaluated by monitoring clinical signs (e.g., diarrhea), quantifying oocyst excretion in feces, and assessing body weight gain. Pharmacokinetic parameters are determined by measuring compound concentrations in plasma samples collected at various time points.
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| ADME/Pharmacokinetics |
The pharmacokinetics of BKI-1369 have been characterized in piglets. Following oral administration, the plasma concentration of BKI-1369 in piglets increased to 11.7 microM during treatment, suggesting constant drug accumulation and sustained exposure of parasites to the drug. The compound has been well characterized for its pharmacokinetic properties in preclinical studies.
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| Toxicity/Toxicokinetics |
BKI-1369 has been evaluated for safety and toxicity in preclinical studies. In piglets, a five-day treatment with BKI-1369 (10 mg/kg twice daily) was well-tolerated without obvious side effects. The compound has been well characterized for its toxicity profile. It is important to note that BKI-1369 increases hERG-inhibitory activity, which is a consideration for its safety profile. The compound is intended for research use only and is not approved for human therapeutic applications.
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| Additional Infomation |
BKI-1369 is a potent and selective bumped kinase inhibitor (BKI) targeting TgCDPK1, developed as a potential treatment for toxoplasmosis and other apicomplexan infections. It has shown broad-spectrum activity against parasites such as Plasmodium falciparum and Cryptosporidium parvum. The compound has been well characterized for its potency, stability, metabolism, toxicity, and pharmacokinetics. BKI-1369 is for research purposes only and is not approved for clinical use.
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| Molecular Formula |
C23H27N7O
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|---|---|
| Molecular Weight |
417.506783723831
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| Exact Mass |
417.227
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| CAS # |
1951431-22-3
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| PubChem CID |
122453014
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| Appearance |
White to off-white solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
586
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=NC2=C(C=C1)C=C(C=C2)C3=NN(C4=NC=NC(=C34)N)CC5CCN(CC5)C
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| InChi Key |
AWJAAKKEYXUCFY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N7O/c1-3-31-19-7-5-16-12-17(4-6-18(16)27-19)21-20-22(24)25-14-26-23(20)30(28-21)13-15-8-10-29(2)11-9-15/h4-7,12,14-15H,3,8-11,13H2,1-2H3,(H2,24,25,26)
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| Chemical Name |
3-(2-ethoxyquinolin-6-yl)-1-[(1-methylpiperidin-4-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine
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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 (~119.76 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.98 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 50.0 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: ≥ 5 mg/mL (11.98 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 50.0 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 | 2.3952 mL | 11.9758 mL | 23.9515 mL | |
| 5 mM | 0.4790 mL | 2.3952 mL | 4.7903 mL | |
| 10 mM | 0.2395 mL | 1.1976 mL | 2.3952 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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