Physicochemical Properties
| Molecular Formula | C22H20F3N5O |
| Molecular Weight | 427.42231464386 |
| Exact Mass | 427.161 |
| CAS # | 1450666-80-4 |
| PubChem CID | 71711915 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 31 |
| Complexity | 596 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC(C1C=CC(=CC=1)C1=C(N)N=CC(C2C=CC(=CC=2)C(N2CCNCC2)=O)=N1)(F)F |
| InChi Key | GGOFGCMPKAWHEZ-UHFFFAOYSA-N |
| 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) |
| Chemical Name | [4-[5-amino-6-[4-(trifluoromethyl)phenyl]pyrazin-2-yl]phenyl]-piperazin-1-ylmethanone |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | PvPI4K 23 nM (IC50) Plasmodium |
| 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]. |
| 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]. |
| 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. |
| References |
[1]. UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria. Antimicrob Agents Chemother. 2018 Aug 27;62(9). pii: e00012-18. |
Solubility Data
| Solubility (In Vitro) | DMSO : 250 mg/mL (584.90 mM) |
| 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. 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. 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 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 | 2.3396 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 |