| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Posaconazole-D5 targets the fungal enzyme lanosterol 14alpha-demethylase (CYP51), a cytochrome P450 enzyme essential for ergosterol biosynthesis in the fungal cell membrane. Inhibition of CYP51 blocks the conversion of lanosterol to ergosterol, leading to accumulation of toxic sterol intermediates and disruption of membrane integrity and function. Posaconazole exhibits broad-spectrum activity against various fungal pathogens including Aspergillus species, Candida species, and Zygomycetes. The deuterated D5 form is used as an analytical internal standard for quantifying Posaconazole in biological matrices and does not alter the target engagement properties of the parent compound.
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| ln Vitro |
In vitro, Posaconazole (parent compound) demonstrates potent antifungal activity against a wide range of clinically significant fungal pathogens. The compound exhibits minimum inhibitory concentrations (MICs) in the sub-micromolar range against Aspergillus fumigatus, Candida albicans, and other opportunistic fungi. Posaconazole shows activity against azole-resistant Candida strains and exhibits fungicidal activity against certain species. The D5-labeled analog is expected to exhibit identical in vitro antifungal activity to the parent compound, as isotopic substitution generally does not substantially affect the compound's interaction with its fungal target. The compound also demonstrates activity against Trypanosoma cruzi and Leishmania species.
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| ln Vivo |
In vivo, Posaconazole (parent compound) is clinically used for the prophylaxis of invasive fungal infections in neutropenic patients and for the treatment of oropharyngeal candidiasis and refractory invasive aspergillosis. The compound exhibits excellent oral bioavailability and extensive tissue distribution, including penetration into the central nervous system. Posaconazole demonstrates efficacy in animal models of disseminated candidiasis, pulmonary aspergillosis, and zygomycosis. The deuterated D5 form serves as an analytical internal standard for pharmacokinetic studies and therapeutic drug monitoring, ensuring accurate quantification of Posaconazole levels in plasma and tissue samples from preclinical and clinical studies.
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| Enzyme Assay |
In vitro enzyme assays for Posaconazole involve measuring lanosterol 14alpha-demethylase (CYP51) activity using fungal microsomal preparations or recombinant enzyme. The assay is performed in buffer containing NADPH as cofactor and radiolabeled or fluorescent substrate (lanosterol or its analogs). Varying concentrations of Posaconazole or the D5 internal standard are incubated with the enzyme at 37degC for 30-60 minutes. The reaction products are extracted and analyzed by HPLC or LC-MS/MS. IC₅0 values for CYP51 inhibition are determined from dose-response curves. The D5 analog is typically used as an internal standard in LC-MS/MS methods rather than as a test compound in enzyme assays.
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| Cell Assay |
Cellular assays for Posaconazole are performed using fungal cell lines or clinical isolates in susceptibility testing. Fungi are cultured in appropriate medium (e.g., RPMI-1640 with MOPS buffer) and seeded in 96-well plates at standardized inoculum densities. Serial dilutions of Posaconazole (0.001-100 microg/mL) are added, and plates are incubated at 35degC for 24-48 hours. Minimum inhibitory concentrations (MICs) are determined visually or spectrophotometrically at 530 nm. For time-kill kinetics, samples are taken at various time points and plated on agar for colony counting. The D5 internal standard is used in LC-MS/MS quantification of Posaconazole in cell lysates or culture supernatants for pharmacokinetic studies.
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| Animal Protocol |
In vivo animal studies for Posaconazole are conducted in rodent models of invasive fungal infections. Immunocompromised mice (e.g., neutropenic or corticosteroid-treated) are inoculated intravenously or intranasally with fungal conidia (Aspergillus or Candida species). Posaconazole is administered orally at doses of 10-50 mg/kg, typically once or twice daily for 7-14 days. Survival, fungal burden in tissues (lungs, kidneys, liver), and histopathological scoring are assessed. Pharmacokinetic studies use the D5 internal standard for accurate LC-MS/MS quantification of Posaconazole in plasma and tissue samples. Efficacy is compared to vehicle control and standard-of-care antifungals.
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| ADME/Pharmacokinetics |
Posaconazole-D5 (CAS#: 1217785-83-5) has molecular formula C3₇H3₇D₅F2N₈O4 and molecular weight 705.81. The parent compound Posaconazole is a broad-spectrum triazole antifungal with oral bioavailability, extensive tissue distribution, and a long elimination half-life (approximately 35 hours). Posaconazole is highly protein-bound (>98%) and undergoes hepatic metabolism primarily via UDP-glucuronosyltransferases (UGTs), with minimal CYP450 metabolism. The D5 internal standard is used in LC-MS/MS bioanalytical methods for therapeutic drug monitoring and pharmacokinetic studies. The compound is soluble in DMSO and should be stored at -20degC.
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| Toxicity/Toxicokinetics |
Toxicological information for Posaconazole-D5 is primarily extrapolated from the parent compound Posaconazole. Posaconazole is generally well-tolerated, with common adverse effects including gastrointestinal disturbances (nausea, vomiting, diarrhea), headache, and liver enzyme elevations (ALT, AST). Hepatotoxicity is rare but requires monitoring. The compound can cause QT interval prolongation and should be used with caution in patients with cardiac conditions. Drug interactions may occur with substrates of CYP3A4. The deuterated D5 form is intended for research use as an analytical standard and is not for human therapeutic use. Standard laboratory precautions should be observed, including use of personal protective equipment.
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| References | |
| Additional Infomation |
Posaconazole-D5 (CAS#: 1217785-83-5) is a deuterium-labeled internal standard for Posaconazole (SCH 56592), a broad-spectrum second-generation triazole antifungal agent. Posaconazole is marketed under the brand name Noxafil and is approved by the FDA for prophylaxis of invasive Aspergillus and Candida infections in neutropenic patients, and for treatment of oropharyngeal candidiasis. The mechanism of action involves inhibition of lanosterol 14alpha-demethylase (CYP51), blocking ergosterol biosynthesis and compromising fungal cell membrane integrity. The D5 analog is used in LC-MS/MS bioanalytical methods for therapeutic drug monitoring, pharmacokinetic studies, and clinical research. For research use only, not for human therapeutic applications.
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| Molecular Formula |
C37H37D5F2N8O4
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| Molecular Weight |
705.80819529
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| Exact Mass |
705.361
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| CAS # |
1217785-83-5
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| Related CAS # |
Posaconazole;171228-49-2
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| PubChem CID |
137628651
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| Appearance |
Off-white to light yellow solid powder
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| Melting Point |
170-172°C
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
51
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| Complexity |
1170
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[2H]C([2H])([2H])C([2H])([2H])[C@@H]([C@H](C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5C[C@](OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F
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| InChi Key |
RAGOYPUPXAKGKH-XNZXKHRISA-N
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| InChi Code |
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1/i1D3,3D2
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| Chemical Name |
4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(3S,4S)-1,1,1,2,2-pentadeuterio-4-hydroxypentan-3-yl]-1,2,4-triazol-3-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4168 mL | 7.0841 mL | 14.1681 mL | |
| 5 mM | 0.2834 mL | 1.4168 mL | 2.8336 mL | |
| 10 mM | 0.1417 mL | 0.7084 mL | 1.4168 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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