Fanotaprim is a dihydrofolate reductase (DHFR) inhibitor (antagonist) with IC50s of 1.57 and 308 nM for tgDHFR (Toxoplasma gondii DHFR) and hDHFR (human DHFR), respectively. Fanotaprim may be used for studying toxoplasmosis.

Physicochemical Properties

Molecular Formula	C19H22N8O
Molecular Weight	378.4310
Exact Mass	378.191
CAS #	2120282-75-7
PubChem CID	134812633
Appearance	Off-white to light yellow solid powder
LogP	1.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	481
Defined Atom Stereocenter Count	0
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]
InChi Key	GUZBZPCNAJDYMO-UHFFFAOYSA-N
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)
Chemical Name	5-[4-[3-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]pyrimidine-2,4-diamine
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

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].
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].
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.
References	[1]. Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis. J Med Chem. 2019;62(3):1562-1576.

Solubility Data

Solubility (In Vitro)

DMSO : 33.33 mg/mL (88.07 mM)

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. 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. 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	2.6425 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.