VT-1598 tosylate is an orally bioactive, selective fungal inhibitor targeting CYP51. VT-1598 tosylate has antifungal activity against Candida albicans. VT-1598 (tosylate) is a reagent for click chemistry. It contains Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing an Azide group.

Physicochemical Properties

Molecular Formula	C38H28F4N6O5S
Molecular Weight	756.724740982056
Exact Mass	756.177
CAS #	2089321-00-4
Related CAS #	VT-1598;2089320-99-8
PubChem CID	166450509
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	11
Heavy Atom Count	54
Complexity	1240
Defined Atom Stereocenter Count	1
SMILES	CC1=CC=C(C=C1)S(=O)(=O)O.C1=CC(=CC=C1COC2=CC=C(C=C2)C#CC3=CN=C(C=C3)C([C@](CN4C=NN=N4)(C5=C(C=C(C=C5)F)F)O)(F)F)C#N
InChi Key	GKPRUVVZIHFHMK-CZCBIWLKSA-N
InChi Code	InChI=1S/C31H20F4N6O2.C7H8O3S/c32-25-10-13-27(28(33)15-25)30(42,19-41-20-38-39-40-41)31(34,35)29-14-9-23(17-37-29)4-1-21-7-11-26(12-8-21)43-18-24-5-2-22(16-36)3-6-24;1-6-2-4-7(5-3-6)11(8,9)10/h2-3,5-15,17,20,42H,18-19H2;2-5H,1H3,(H,8,9,10)/t30-;/m0./s1
Chemical Name	4-[[4-[2-[6-[(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]benzonitrile;4-methylbenzenesulfonic acid
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	CYP51[1]
ln Vitro	Clinical Candida (C. auris) is inhibited in vitro by VT-1598 tosylate (0.015-8 μg/mL; 24 h) [1]. Clinical Candida (C. auris) growth is significantly inhibited in vitro by VT-1598 tosylate (0.03125-0.125 μg/mL; 24 h) [2].
ln Vivo	In addition to providing mice with a dose-dependent survival advantage, VT-1598 tosylate (oral gavage; 5, 15, and 50 mg/kg; once daily; 7 days) significantly decreases the fungal load in mice[1]. Act1-deficient mice infected with C had a lot of VT-1598 tosylate (or gavage; 3.2, 8, and 20 mg/kg; once daily; 4 days) in their tongue and plasma. Candida albicans[2].
Animal Protocol	Animal/Disease Models: Mice model of invasive candidiasis[1] Doses: 5 mg/kg, 15 mg/kg, and 50 mg/kg Route of Administration: Oral gavage; one time/day; 7 days Experimental Results: Observed median survival in the VT-1598 15 mg /kg and 50 mg/kg groups (15 days and >21 days, respectively) longer than the control group. Observed kidney fungal burden in mice treated with 15 mg/kg and 50 mg/kg doses (mean log10 CFU/g, 5.40 and 3.67, respectively) lower than the vehicle control group. demonstrated mean trough concentrations 1.55 μg/mL after 7 days of therapy in the 5 mg/kg group, 6.78 μg/mL in the 15 mg/kg group, and 14.2 μg/mL in the 50 mg/kg group. Animal/Disease Models: Act1-deficient mice infected with C. albicans[2] Doses: 3.2, 8, and 20 mg/kg Route of Administration: Oral gavage; one time/day; 4 days Experimental Results: Resulted in high concentrations in the plasma and tongues of Candida-infected mice.
References	[1]. Nathan P Wiederhold, et al. The Fungal Cyp51-Specific Inhibitor VT-1598 Demonstrates In Vitro and In Vivo Activity against Candida auris. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02233-18. [2]. Timothy J Break, et al. VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice. J Antimicrob Chemother. 2018 Aug 1;73(8):2089-2094.

Solubility Data

Solubility (In Vitro)

DMSO: 150 mg/mL (198.22 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.30 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 25.0 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: ≥ 2.5 mg/mL (3.30 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 25.0 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	1.3215 mL	6.6075 mL	13.2149 mL
	5 mM	0.2643 mL	1.3215 mL	2.6430 mL
	10 mM	0.1321 mL	0.6607 mL	1.3215 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.