| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Sterol 14α-demethylase (CYP51A and CYP51B). PC945 inhibits lanosterol 14α-demethylase, a key enzyme in ergosterol biosynthesis, leading to disruption of fungal cell membranes. The compound demonstrates strong inhibitory activity against both CYP51A and CYP51B.
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| 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].
PC945 demonstrates potent antifungal activity against azole-susceptible strain NCPF2010 with an MIC value of 0.063 µg/mL. It inhibits CYP51A and CYP51B with IC50 values of 0.23 μM and 0.22 μM, respectively. The compound exhibits efficacy against a wide variety of both azole-susceptible and azole-resistant strains of A. fumigatus. |
| ln Vivo |
Intranasally administered once daily for seven days, PC945 (0.56-14 μg/mouse) effectively prevents rolling behavior [1].
PC945 is designed to be administered via inhalation for high local lung concentrations and limited systemic exposure. In preclinical testing, the compound demonstrates potent in vivo antifungal activity against respiratory fungal infections. Its long-acting properties support once-daily dosing regimens. |
| Enzyme Assay |
Enzyme inhibition assays are performed using recombinant CYP51A and CYP51B enzymes. PC945 is incubated with the enzyme and substrates, and the inhibition of sterol 14α-demethylase activity is measured. IC50 values of 0.23 μM and 0.22 μM are determined.
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| Cell Assay |
Antifungal susceptibility testing is conducted using broth microdilution methods following CLSI guidelines. A variety of A. fumigatus strains, including azole-susceptible and azole-resistant isolates, are tested. Minimum inhibitory concentrations (MIC) are determined, with PC945 showing an MIC of 0.063 µg/mL against susceptible strains.
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| 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. In vivo efficacy of PC945 is evaluated in animal models of invasive pulmonary aspergillosis, such as immunocompromised mice infected with A. fumigatus. The compound is administered via inhalation, and fungal burden, survival, and histopathological changes are assessed. |
| ADME/Pharmacokinetics |
PC945 is designed for inhalation, achieving high local concentrations in the lungs with limited systemic exposure. This targeted delivery approach minimizes systemic side effects while maximizing antifungal efficacy at the site of infection. Detailed PK parameters are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicity studies for PC945 focus on the respiratory tract due to its inhaled route of administration. Preclinical testing evaluates local tolerance and potential systemic toxicity. The compound's targeted delivery approach is expected to minimize systemic adverse effects compared to systemically administered azoles.
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| References |
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| Additional Infomation |
Opeconazole is a synthetic triazole antifungal drug active against a variety of pathogenic fungi and is used to treat invasive pulmonary aspergillosis. Through nebulized inhalation, oppeconazole is delivered in high concentrations to the lungs and remains in lung tissue for an extended period, with extremely low systemic exposure. Opeconazole selectively binds to and inhibits the activity of CYP450-dependent 14α-sterol demethylase in fungi, thereby preventing the production of ergosterol, an important component of the fungal cell membrane. This leads to fungal cell lysis and inhibits pulmonary fungal infection.
PC945 (Opelconazole) is a novel antifungal triazole in development for the treatment of respiratory fungal infections, particularly invasive aspergillosis. Its design for inhalation allows for high local lung concentrations with limited systemic exposure. The compound is not yet approved for clinical use. |
| Molecular Formula |
C38H37F3N6O3
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|---|---|
| Molecular Weight |
682.733999013901
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| Exact Mass |
682.287
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| CAS # |
1931946-73-4
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| PubChem CID |
121383526
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
50
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
2
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| 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
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| InChi Key |
OSAMZQJKSCAOHA-CWRQMEKBSA-N
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| 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
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| 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
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| Synonyms |
PC945; PC-945
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~146.47 mM)
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|---|---|
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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