| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
PvPI4K 23 nM (IC50) Plasmodium
UCT943 targets Plasmodium falciparum phosphatidylinositol 4-kinase (PI4K). PI4K is a key enzyme in the phosphoinositide signaling pathway essential for parasite survival. The compound shows >200-fold selectivity for parasite PI4K over human PI4Kβ isoenzyme (IC50 = 5.4 μM). |
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| ln Vitro |
UCT943's in vitro cytotoxicity is evaluated using 50% cytotoxic concentrations (CC50s) of 12, 17, 113, and 13 μM against L6 cells, Chinese hamster ovary (CHO), Vero, and HepG2 cells, respectively[1].
UCT943 inhibits P. falciparum PI4K with an IC50 of 23 nM. In vitro cytotoxicity is evaluated using CC50 values of 12, 17, 113, and 13 μM against L6 cells, CHO, Vero, and HepG2 cells, respectively. UCT943 displays higher activity against resistant P. falciparum and P. vivax compared to MMV048. |
| ln Vivo |
UCT943 demonstrates exceptional in vivo efficacy in the mouse models of P. falciparum NSG (NOD-scid IL-2R³null) (0.01, 0.1, 0.3, 1.1, and 10 mg/kg; oral administration; once per day; 4 days) and Plasmodium berghei (10 mg/kg and 3 mg/kg; oral administration; daily; 4 days). In the mouse model of P. berghei infection, UCT943 decreases parasitemia by >99.9% when dosed at 10 mg/kg per os (po) and heals all mice, with >30 mean survival days (MSD). At 3 mg/kg po, parasitemia is reduced by 99%, but there is no total cure; MSD lasts 10 days. In the P. berghei infection paradigm, the 90% effective dosage (ED90) is 1.0 mg/kg po. The NSG mouse model infected with P. falciparum has an ED90 of 0.25 mg/kg[1].
In vivo activity data for UCT943 are limited. As a next-generation antimalarial PI4K inhibitor, it is expected to have efficacy in mouse models of malaria. Further in vivo studies are needed to fully characterize its antimalarial efficacy and pharmacokinetic properties. |
| Enzyme Assay |
In vitro enzyme assays measure PI4K inhibition using recombinant Plasmodium PI4K enzyme. IC50 values are determined by assessing kinase activity in the presence of varying concentrations of UCT943. Selectivity is confirmed by testing against human PI4Kβ isoenzyme.
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| Cell Assay |
Cell-based assays measure antimalarial activity against P. falciparum and P. vivax in infected red blood cell cultures. Cytotoxicity is assessed in mammalian cell lines including L6, CHO, Vero, and HepG2 cells. CC50 values are determined to evaluate the therapeutic window.
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| Animal Protocol |
Animal/Disease Models: Mice with P. berghei and P. falciparum NOD-scid IL-2Rγnull (NSG) models[1]
Doses: 10 mg/kg and 3 mg/kg for P. berghei model; 0.01, 0.1, 0.3, 1.1 and 10 mg/kg for P. falciparum NOD-scid IL-2Rγnull (NSG) model Route of Administration: Oral administration; daily; 4 days for P. berghei model Oral administration; once per day; 4 days for P. falciparum NOD-scid IL- 2Rγnull (NSG) model Experimental Results: The ED90 is 1.0 mg/kg in the P. berghei infection model. The ED90 is 0.25 mg/kg in the P. falciparum-infected NSG mouse model. In vivo efficacy is evaluated in mouse models of malaria. The compound's ability to reduce parasitemia and prevent mortality is assessed. Further studies are needed to fully characterize its in vivo antimalarial activity and pharmacokinetic properties. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for UCT943 are limited. As a small molecule PI4K inhibitor, it may have favorable oral bioavailability. Further pharmacokinetic studies are needed to determine its absorption, distribution, metabolism, and excretion properties in animal models.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for UCT943 are limited. The compound shows good selectivity for parasite PI4K over human PI4Kβ (IC50 = 5.4 μM), suggesting a favorable safety profile. Standard laboratory safety precautions should be followed. Further toxicological studies are needed.
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| References | |
| Additional Infomation |
UCT943 is a next-generation Plasmodium falciparum PI4K inhibitor with an IC50 of 23 nM. It shows >200-fold selectivity for parasite PI4K over human PI4Kβ and displays higher activity than MMV048 against resistant parasites. UCT943 is a valuable research tool for antimalarial drug discovery and has potential as a therapeutic agent for malaria.
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| Molecular Formula |
C22H20F3N5O
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|---|---|
| Molecular Weight |
427.42231464386
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| Exact Mass |
427.161
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| CAS # |
1450666-80-4
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| PubChem CID |
71711915
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
596
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C=CC(=CC=1)C1=C(N)N=CC(C2C=CC(=CC=2)C(N2CCNCC2)=O)=N1)(F)F
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| InChi Key |
GGOFGCMPKAWHEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20F3N5O/c23-22(24,25)17-7-5-15(6-8-17)19-20(26)28-13-18(29-19)14-1-3-16(4-2-14)21(31)30-11-9-27-10-12-30/h1-8,13,27H,9-12H2,(H2,26,28)
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| Chemical Name |
[4-[5-amino-6-[4-(trifluoromethyl)phenyl]pyrazin-2-yl]phenyl]-piperazin-1-ylmethanone
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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 : 250 mg/mL (584.90 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.87 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 20.8 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: ≥ 2.08 mg/mL (4.87 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 20.8 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: ≥ 2.08 mg/mL (4.87 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 | 2.3396 mL | 11.6981 mL | 23.3962 mL | |
| 5 mM | 0.4679 mL | 2.3396 mL | 4.6792 mL | |
| 10 mM | 0.2340 mL | 1.1698 mL | 2.3396 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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