PC945 is a potent antifungal triazole active molecule that is resistant to a variety of sensitive and drug-resistant Aspergillus fumigatus strains. PC945 is a potent, tight-binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A/CYP51B) activity with IC50s of 0.23 μM and 0.22 μM, respectively.

Physicochemical Properties

Molecular Formula	C38H37F3N6O3
Molecular Weight	682.733999013901
Exact Mass	682.287
CAS #	1931946-73-4
PubChem CID	121383526
Appearance	Light yellow to yellow solid powder
LogP	6.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	10
Heavy Atom Count	50
Complexity	1090
Defined Atom Stereocenter Count	2
SMILES	FC1C=C(C=CC=1[C@@]1(CN2C=NC=N2)C[C@H](COC2C=CC(=CC=2C)N2CCN(C3C=CC(C(NC4C=CC(=CC=4)F)=O)=CC=3)CC2)CO1)F
InChi Key	OSAMZQJKSCAOHA-CWRQMEKBSA-N
InChi Code	InChI=1S/C38H37F3N6O3/c1-26-18-33(46-16-14-45(15-17-46)32-9-2-28(3-10-32)37(48)44-31-7-4-29(39)5-8-31)11-13-36(26)49-21-27-20-38(50-22-27,23-47-25-42-24-43-47)34-12-6-30(40)19-35(34)41/h2-13,18-19,24-25,27H,14-17,20-23H2,1H3,(H,44,48)/t27-,38+/m1/s1
Chemical Name	4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]-3-methylphenyl]piperazin-1-yl]-N-(4-fluorophenyl)benzamide
Synonyms	PC945; PC-945
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	PC945 is a triazole antifungal medication that is administered via inhalation [1]. PC945 has the highest antifungal activity against the azole-sensitive strain NCPF2010, with a MIC of 0.063 µg/mL [2].
ln Vivo	Intranasally administered once daily for seven days, PC945 (0.56-14 μg/mouse) effectively prevents rolling behavior [1].
Animal Protocol	Animal/Disease Models: Specific pathogen-free A/J mice (male, 5 weeks old, lung Aspergillus infection) [1] Doses: 0.56, 2.8, 14 μg/mouse (intranasal administration of 0.016-, 0.08-, and 0.4- mg)/ml suspension, respectively) Route of Administration: intranasally; one time/day for 7 days Experimental Results: Dramatically inhibited the occurrence of rolling behavior.
References	[1]. In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02280-16. [2]. Antifungal synergy of a topical triazole, PC945, with a systemic triazole against respiratory Aspergillus fumigatus infection. Sci Rep. 2019 Jul 1;9(1):9482.
Additional Infomation	Opelconazole is a synthetic triazole antifungal agent, with activity against a variety of pathogenic fungi that can potentially be used against invasive pulmonary aspergillosis. Upon inhalation by nebulizer, opelconazole is delivered in high concentrations to the lungs and resides in the lung tissues for a long period of time with minimal systemic exposure. Opelconazole selectively binds to and inhibits the CYP450-dependent 14-alpha-sterol demethylase in fungi, thereby preventing the production of ergosterol, which is an essential constituent of the fungal cell membrane. This results in fungal cell lysis and inhibits fungal infection in the lungs.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~146.47 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (3.66 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (3.66 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	1.4647 mL	7.3235 mL	14.6471 mL
	5 mM	0.2929 mL	1.4647 mL	2.9294 mL
	10 mM	0.1465 mL	0.7324 mL	1.4647 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.