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

Physicochemical Properties

Molecular Formula	C31H20F4N6O2
Molecular Weight	584.523119926453
Exact Mass	584.158
CAS #	2089320-99-8
Related CAS #	VT-1598 tosylate;2089321-00-4
PubChem CID	126715974
Appearance	Off-white to light yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	770.9±70.0 °C at 760 mmHg
Flash Point	420.0±35.7 °C
Vapour Pressure	0.0±2.8 mmHg at 25°C
Index of Refraction	1.614
LogP	6.56
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	10
Heavy Atom Count	43
Complexity	1030
Defined Atom Stereocenter Count	1
SMILES	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	UDGASIIGNCBLSI-PMERELPUSA-N
InChi Code	InChI=1S/C31H20F4N6O2/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/h2-3,5-15,17,20,42H,18-19H2/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
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	In vitro action against C is demonstrated by VT-1598 (0.015-8 μg/mL; 24 h). auris[1]. Clinical Candida isolates' in vitro growth is significantly inhibited by VT-1598 (0.03125-0.125 μg/mL; 24 h)[2].
ln Vivo	In Act1-deficient mice infected with Candida albicans (C. albicans), treatment of electrodes with VT-1598 (oral gavage; 5, 15, and 50 mg/kg; once daily; 7 days) produced a dose-dependent survival advantage. Moreover, VT-1598 was paired with an electrode to reduce VT-1598 within the electrode ( Lateral gavage; 3.2, 8, and 20 mg/kg; once daily; 4 days) ductal and lingual fungal burden [1].
Cell Assay	Cell viability assay[2] Cell Types: 28 Candida isolates obtained from mucosal sites of APECED patients Tested Concentrations: 0.03125-0.125 μg/mL Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated effective in vitro activity against all 28 isolates (MIC range=0.03125-0.125 mg/L), with MIC50 and MIC90 values of 0.0625 and 0.125 respectively mg/L.
Animal Protocol	Animal/Disease Models: Mouse model of invasive candidiasis [1] Doses: 5, 15, 50 mg/kg Route of Administration: po (oral gavage); present in large amounts [2]. one time/day; 7 days Experimental Results: Median survival was observed to be longer in the VT-1598 15 mg/kg and 50 mg/kg groups (15 days and >21 days, respectively) than in the control group. The observed renal fungal burden in mice treated with the 15 mg/kg and 50 mg/kg doses (mean log10 CFU/g, 5.40 and 3.67, respectively) was lower than that in the vehicle control group. After 7 days of treatment, the average trough concentration in the 5 mg/kg group was 1.55 μg/mL, the average trough concentration in the 15 mg/kg group was 6.78 μg/mL, and the average trough concentration in the 50 mg/kg group was 14.2 μg/mL. Animal/Disease Models: Act1-deficient mice infected with Candida albicans[2] Doses: 3.2, 8 and 20 mg/kg Route of Administration: po (oral gavage); one time/day; 4 days Experimental Results: Plasma and tongue of Candida-infected mice The concentration is very high.
References	[1]. 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]. 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 : ~100 mg/mL (~171.08 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7108 mL	8.5540 mL	17.1081 mL
	5 mM	0.3422 mL	1.7108 mL	3.4216 mL
	10 mM	0.1711 mL	0.8554 mL	1.7108 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.