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| Targets |
Fanotaprim targets dihydrofolate reductase (DHFR) from Toxoplasma gondii (TgDHFR), an essential enzyme in the folate synthesis pathway required for DNA replication and cell division. It exhibits potent inhibition of TgDHFR with an IC₅₀ of 1.57 nM and shows 200-fold selectivity over human DHFR (hDHFR, IC₅₀ = 308 nM). By selectively inhibiting TgDHFR, Fanotaprim blocks the production of tetrahydrofolate, a cofactor essential for nucleotide synthesis, thereby inhibiting parasite growth.
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| ln Vitro |
Fanotaprim exhibits antiproliferative and parasiticidal actions against the type I RH strain of T, with EC50 values of 13 and 7300 nM, respectively. MCF-7 and Gondii cells, in that order[1]. Fanotaprim has the capacity to stop T cells from growing. gondii strains in vitro(GT1, ME49, CTG, RUB, and VAND) with EC50s spanning 7.6~ 29.8 nM[1].
In vitro, Fanotaprim demonstrates potent inhibition of TgDHFR with an IC₅₀ of 1.6 nM and 200-fold selectivity over hDHFR. It exhibits antiproliferative and parasiticidal actions against the type I RH strain of T. gondii with EC₅₀ values of 13 nM and 7300 nM, respectively. Fanotaprim shows similar potency across multiple parasite lineages in cell-based parasite growth assays. These in vitro activities support its potential for treating toxoplasmosis. |
| ln Vivo |
Fanotaprim (1–10 mg/kg; po; daily; starting on day 1 and ending on day 7) has demonstrated remarkable efficacy in managing acute infection caused by extremely pathogenic strains of T. gondii in the model used on mice[1]. The CL, Vd, and t1/2 values of fanotaprim (1 mg/kg; iv; mouse) are 10.6 mL/min/kg, 1.14 L/kg, and 3.9 hours, correspondingly[1]. F, Cmax, Tmax, and AUC0-last of 47.3%, 178 ng/mL, 0.05 hours, and 750 ng h/mL, respectively, are displayed by fanotaprim (0.83 mg/kg; po; mouse)[1].
In vivo, Fanotaprim demonstrates efficacy in a murine model of acute toxoplasmosis. It was effective in radical cure of acute infection with the highly virulent type I RH strain in the murine model. Fanotaprim (VYR-006) showed anti-parasiticidal activity in vivo. These results support its potential for treating Toxoplasma gondii infections. The compound is primarily used as a research tool for studying toxoplasmosis and DHFR inhibitors. |
| Enzyme Assay |
The in vitro DHFR inhibition assay for Fanotaprim uses recombinant TgDHFR and hDHFR enzymes and a substrate such as dihydrofolate. Enzyme activity is measured by monitoring the reduction of the substrate, and IC₅₀ values are calculated from dose-response curves. Antiparasitic activity is assessed in T. gondii-infected cells by measuring parasite growth or replication. EC₅₀ values are determined from dose-response curves. Selectivity is calculated by comparing IC₅₀ values for TgDHFR and hDHFR.
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| Cell Assay |
Cellular assays for Fanotaprim are conducted in T. gondii-infected cell lines. Cells are infected with the parasite and treated with varying concentrations of the compound. Parasite growth is measured by quantifying parasite replication, plaque formation, or reporter gene expression. EC₅₀ values are calculated from dose-response curves. Host cell viability is assessed to confirm that antiparasitic activity is not due to cytotoxicity. The compound's selectivity for parasite DHFR over human DHFR is confirmed by comparing activities.
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| Animal Protocol |
Animal/Disease Models: CD-1female mice (murine model of acute toxoplasmosis)[1]
Doses: 1-10 mg/kg Route of Administration: po; daily; beginning on day 1 through day 7 Experimental Results: Mice were monitored for survival for 30 days within termittent IVIS monitoring. At doses of 10 mg/kg Fanotaprim, qd or bid for 7 days, yielded 100% survival for 30 days. In vivo studies for Fanotaprim are conducted in murine models of acute toxoplasmosis. Mice are infected with the highly virulent type I RH strain of T. gondii and treated with Fanotaprim. Efficacy is assessed by measuring parasite clearance, survival rates, and clinical signs of infection. The compound is administered orally or via injection at doses determined by pharmacokinetic studies. Pharmacodynamic markers such as parasite load in tissues are evaluated. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Fanotaprim is not extensively reported in publicly available sources. The compound has a molecular weight of 378.43 g/mol and a molecular formula of C₁₉H₂₂N₈O. It has a solubility of 10 mM in DMSO. As a small molecule DHFR inhibitor, it is expected to have moderate bioavailability. Detailed PK parameters such as half-life and bioavailability are not available in the current literature for this research compound.
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| Toxicity/Toxicokinetics |
Toxicity data for Fanotaprim is derived from in vivo studies in murine models of toxoplasmosis. The compound's 200-fold selectivity for TgDHFR over hDHFR suggests a favorable safety profile. As with all research compounds, Fanotaprim is intended for research use only and not for human therapeutic applications. Standard in vitro cytotoxicity assays and comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
Fanotaprim (VYR-006) is a potent, selective Toxoplasma gondii DHFR inhibitor with an IC₅₀ of 1.6 nM and 200-fold selectivity over human DHFR. It is a pyrimidine-class antifolate that demonstrates anti-parasiticidal activity in vitro and in vivo. Fanotaprim exhibits antiproliferative and parasiticidal actions against the type I RH strain of T. gondii with EC₅₀ values of 13 nM and 7300 nM, respectively. It was effective in radical cure of acute infection with the highly virulent type I RH strain in a murine model. Fanotaprim has the molecular formula C₁₉H₂₂N₈O and a molecular weight of 378.43 g/mol.
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| Molecular Formula |
C19H22N8O
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| Molecular Weight |
378.4310
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| Exact Mass |
378.191
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| CAS # |
2120282-75-7
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| PubChem CID |
134812633
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
481
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1=NC([H])=C(C([H])=N1)C1C([H])=C([H])C([H])=C(C=1[H])N1C([H])([H])C([H])([H])N(C2=C([H])N=C(N([H])[H])N=C2N([H])[H])C([H])([H])C1([H])[H]
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| InChi Key |
GUZBZPCNAJDYMO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H22N8O/c1-28-19-23-10-14(11-24-19)13-3-2-4-15(9-13)26-5-7-27(8-6-26)16-12-22-18(21)25-17(16)20/h2-4,9-12H,5-8H2,1H3,(H4,20,21,22,25)
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| Chemical Name |
5-[4-[3-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]pyrimidine-2,4-diamine
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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 : 33.33 mg/mL (88.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.61 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.50 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.50 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 | 2.6425 mL | 13.2125 mL | 26.4250 mL | |
| 5 mM | 0.5285 mL | 2.6425 mL | 5.2850 mL | |
| 10 mM | 0.2642 mL | 1.3212 mL | 2.6425 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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