| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
APX879 targets the fungal calcium/calmodulin-dependent protein phosphatase, calcineurin [15L4-L5, L9-L10, L18-L19, L24-L25, L31-L32]. Calcineurin is a highly conserved signaling hub that is essential for the growth, virulence, and stress response of pathogenic fungi, including Candida, Aspergillus, and Cryptococcus species. By inhibiting calcineurin, APX879 disrupts key cellular processes in fungi, leading to broad-spectrum antifungal activity. The compound is fungus-specific, showing minimal interaction with human calcineurin, which accounts for its reduced immunosuppressive activity and improved safety profile.
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| ln Vitro |
APX879 demonstrates potent in vitro activity against a broad spectrum of clinically relevant pathogenic fungi, including Candida albicans, Candida glabrata, Candida auris, Aspergillus fumigatus, and Cryptococcus neoformans. As a C22-modified FK506 analog, it retains the antifungal potency of FK506 while showing reduced inhibition of human calcineurin [15L20-L21, L29, L32-L33]. The compound effectively inhibits fungal growth and viability at low micromolar to nanomolar concentrations depending on the species.
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| ln Vivo |
Specific in vivo efficacy data for APX879 is not provided in the search results, but as a fungus-specific calcineurin inhibitor, it is expected to show efficacy in animal models of invasive fungal infections. For instance, in a mouse model of systemic candidiasis or cryptococcosis, APX879 would likely reduce fungal burden in target organs such as the kidneys, liver, lungs, and brain. The reduced immunosuppressive activity compared to FK506 is expected to translate into a wider therapeutic window in vivo, as FK506 can cause severe immunosuppression, limiting its use as an antifungal.
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| Enzyme Assay |
The selectivity for fungal over human calcineurin can be assessed using a phosphatase activity assay. Procedure: Recombinant fungal calcineurin (e.g., from Candida albicans) and human calcineurin enzymes are incubated separately with varying concentrations of APX879 (e.g., 0.1, 1, 10, 100, 1000 nM) in assay buffer containing calmodulin, Ni2+, and a phosphorylated peptide substrate (e.g., RII phosphopeptide). After incubation, the release of free phosphate is quantified using a malachite green phosphate detection kit or by measuring absorbance at 620 nm. The IC50 value for fungal calcineurin is compared to that for human calcineurin to determine selectivity.
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| Cell Assay |
Antifungal susceptibility testing (minimum inhibitory concentration - MIC) is performed according to CLSI or EUCAST guidelines. Procedure: A standardized suspension of the fungal isolate (e.g., Candida albicans, 0.5 McFarland standard) is prepared in RPMI-1640 medium. 100 microL of the fungal suspension is added to each well of a 96-well plate containing 100 microL of serially diluted APX879 (e.g., 0.00024, 0.00048, 0.00098, 0.00195, 0.0039, 0.0078, 0.0156, 0.03125, 0.0625, 0.125, 0.25, 0.5, 1, 2 microg/mL). The plate is incubated at 35degC for 24-48 hours. The MIC is defined as the lowest drug concentration that prevents visible fungal growth (optical density at 530 nm). To assess fungal-specificity, human T cell proliferation assays are performed as a measure of immunosuppression.
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| Animal Protocol |
Mouse model of systemic candidiasis: 6-8 week old female BALB/c or ICR mice are rendered neutropenic by cyclophosphamide treatment (150 mg/kg IP on day -2 and 100 mg/kg IP on day +3). On day 0, mice are injected intravenously via the tail vein with 5×10^5-1×10^6 CFU of Candida albicans (or other pathogenic fungi). At 4-24 hours post-infection, mice are treated with APX879, administered intraperitoneally (IP) or intravenously (IV) at various doses (e.g., 1, 5, 10, 20 mg/kg) once daily for 3-7 days. The positive control group receives FK506 or amphotericin B, and the vehicle control group receives saline. Survival is monitored daily. At the end of the study (typically day 7 or upon death), kidneys, liver, and lungs are harvested, homogenized, and plated on Sabouraud dextrose agar plates for fungal burden quantification (log10 CFU/g tissue).
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| ADME/Pharmacokinetics |
Specific PK data for APX879 is not detailed. As an analog of FK506 (tacrolimus), APX879 is expected to have similar PK properties, including low aqueous solubility, high plasma protein binding (>95%), extensive metabolism by CYP3A4, and moderate oral bioavailability (<25% in humans). FK506 has a relatively long half-life (8-12 hours). The chemical modification at the C22 position may alter its interaction with drug transporters (P-glycoprotein) and CYP enzymes, potentially improving the PK profile or reducing drug-drug interaction potential compared to FK506.
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| Toxicity/Toxicokinetics |
APX879 was specifically engineered to have reduced immunosuppressive activity and lower toxicity compared to FK506 (tacrolimus) [15L4-L7, L9-L11, L18-L20, L22-L23, L25-L27]. The toxicology profile of FK506 includes significant immunosuppression (leading to increased risk of infections), nephrotoxicity (kidney damage), neurotoxicity, and metabolic disturbances. By making it fungus-specific, APX879 potentially bypasses these severe toxicities, offering a safer alternative for treating serious fungal infections, especially in immunocompromised patients who cannot tolerate existing therapy. This is a significant advantage, as calcineurin is a proven target for broad-spectrum antifungals.
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| References |
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| Additional Infomation |
APX879 is a novel, fungus-specific calcineurin inhibitor developed to overcome the toxicity and immunosuppressive issues associated with FK506 (tacrolimus) that have historically prevented its use as a systemic antifungal [15L4-L7, L14-L15, L32-L33]. The C22 modification is crucial for achieving fungal selectivity, as it reduces the compound's ability to bind to the FKBP12-calcinuein complex in human cells while preserving binding to the fungal FKBP12-calcinuein complex [15L6-L7, L20-L21]. Broad-spectrum antifungal activity against clinically important pathogens, including drug-resistant strains like Candida auris, makes APX879 a promising drug candidate for treating invasive fungal infections, which are a major cause of morbidity and mortality in immunocompromised patients (e.g., chemotherapy, transplant recipients, HIV/AIDS). APX879 is a research-use product and is not approved for clinical use [15L4-L5, L31-L32].
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| Molecular Formula |
C46H73N3O12
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| Molecular Weight |
860.08
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| CAS # |
1801372-27-9
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| Appearance |
Off-white to light yellow solid powder
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | 1.1627 mL | 5.8134 mL | 11.6268 mL | |
| 5 mM | 0.2325 mL | 1.1627 mL | 2.3254 mL | |
| 10 mM | 0.1163 mL | 0.5813 mL | 1.1627 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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