BF738735 is a phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ) inhibitor (antagonist) with IC50 of 5.7 nM.

Physicochemical Properties

Molecular Formula	C21H19FN4O3S
Molecular Weight	426.463966608047
Exact Mass	426.116
CAS #	1436383-95-7
PubChem CID	135742054
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.672
LogP	2.68
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	690
Defined Atom Stereocenter Count	0
InChi Key	IMHZCCZYPHJVMS-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H19FN4O3S/c1-13-19(15-6-7-18(27)17(22)11-15)26-9-8-23-20(21(26)25-13)24-12-14-4-3-5-16(10-14)30(2,28)29/h3-11,27H,12H2,1-2H3,(H,23,24)
Chemical Name	2-fluoro-4-[2-methyl-8-[(3-methylsulfonylphenyl)methylamino]imidazo[1,2-a]pyrazin-3-yl]phenol
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	BF738735 (Compound 1) exhibits a substantial inhibitory effect on PI4KIIIβ activity in vitro, with an IC50 of 5.7 nM. PI4KIIIα is also harmed by BF738735, however not until 300 times greater concentrations (IC50 of 1.7 μM) are reached. Furthermore, BF738735's activity was examined using a panel of 150 cellular kinases, including 13 lipid kinases at a 10 μM dose. In vitro inhibition of PI4KIIIβ is unique to BF738735, as evidenced by inhibition rates for all kinases being less than 10%. With 50% effective doses ranging from 4 to 71 nM, BF738735 has broad-spectrum antiviral action and inhibits all enterovirus and rhinovirus species tested. All viruses examined were successfully suppressed by BF738735, with EC50 values ranging from 4 to 71 nM. Analyzed concurrently with EC50 and under identical culture circumstances for a duration of 3 to 4 days, BF738735 demonstrated lower cytotoxicity, with CC50 values varying between 11 and 65 μM, culminating in a notable selectivity index. Low BF738735 concentrations decreased luciferase levels to the GuaHCl treatment level, suggesting that BF738735 inhibits the replication of viral RNA. In this experiment, BF738735's EC50 of 77 nM is similar to the inhibition seen in a multicycle assay for coxsackievirus serotype B3 (CVB3) [1].
ln Vivo	Good plasma levels of antiviral medications were present in the samples, and BF738735 was well tolerated. At the 25 mg/kg dose, full inhibition was seen, while at the 5 mg/kg dose, some inhibition was noted [2].
References	[1]. A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ. Antimicrob Agents Chemother. 2013 Oct;57(10):4971-81. [2]. V Saarnio. Antiviral Molecules of Enteroviruses. 13.1.2017.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~293.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.88 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 (4.88 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 (4.88 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	2.3449 mL	11.7244 mL	23.4489 mL
	5 mM	0.4690 mL	2.3449 mL	4.6898 mL
	10 mM	0.2345 mL	1.1724 mL	2.3449 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.