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| 5mg |
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| Targets |
Gwt1 (fungal enzyme). APX-2039 is an orally active inhibitor of the fungal Gwt1 enzyme, which is involved in GPI (glycosylphosphatidylinositol) anchoring of cell wall mannoproteins. By inhibiting Gwt1, APX-2039 blocks GPI anchoring, disrupting cell wall integrity and killing fungal cells. It shows potent activity against Cryptococcus species and other pathogenic fungi.
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| ln Vitro |
APX-2039 is a potent small molecule inhibitor of fungal Gwt1, with MICs of 0.008-0.031 microg/mL against C. neoformans, C. gattii, and Candida albicans. The compound demonstrates strong anti-cryptococcal activity and excellent potency in vitro against clinically relevant fungal pathogens, including drug-resistant strains.
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| ln Vivo |
APX-2039 is orally active and has been evaluated in a rabbit model of cryptococcal meningitis. The compound shows efficacy in this model, confirming its potential for treating CM. Further in vivo studies have demonstrated its ability to block GPI anchoring and reduce fungal burden in infected tissues.
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| Enzyme Assay |
Not explicitly detailed in reference sources. A typical Gwt1 enzyme assay involves incubating purified recombinant Gwt1 with APX-2039 and measuring the enzymatic conversion of GPI precursors. Alternatively, a fungal whole-cell assay measuring GPI-anchored protein localization by flow cytometry or Western blot can be used to assess compound activity.
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| Cell Assay |
Not explicitly detailed in reference sources. A standard antifungal susceptibility assay is performed according to CLSI guidelines. Cryptococcal isolates (e.g., C. neoformans H99) are incubated with APX-2039 in RPMI-1640 medium in 96-well plates at 35degC for 72 hours, and MIC is determined as the lowest concentration preventing visible growth. The MIC values are reported as 0.008-0.031 microg/mL.
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| Animal Protocol |
In the rabbit model of cryptococcal meningitis, rabbits are infected intrathecally with C. neoformans and then treated with APX-2039 at various doses, administered orally. Fungal burden is quantified by CFU counts in cerebrospinal fluid and brain tissue. The compound's efficacy is assessed by reduction in fungal burden compared to vehicle control.
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| ADME/Pharmacokinetics |
APX-2039 is orally bioavailable with a molecular weight of 362.36 and formula C20H15FN4O2. It is soluble in DMSO (100 mg/mL, 275.97 mM). For oral administration, it can be formulated in appropriate vehicles. As a prodrug, APX-2039 is converted to the active Gwt2096 inhibitor APX1 in vivo. Storage should be at -20degC.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for APX-2039 are provided in the reference sources. As an antifungal agent in preclinical development, comprehensive safety pharmacology and toxicology studies would be required before clinical use. The compound is for research use only and should be handled with appropriate safety precautions.
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| References | |
| Additional Infomation |
APX-2039 is a research compound not yet approved for clinical use. It is being developed as an oral antifungal therapy for cryptococcal meningitis, a life-threatening opportunistic infection. As a Gwt1 inhibitor, it represents a novel antifungal class with a mechanism distinct from current therapies, offering potential for treating resistant infections. The compound shows excellent in vitro potency and oral bioavailability.
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| Molecular Formula |
C20H15FN4O2
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|---|---|
| Molecular Weight |
362.36
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| Exact Mass |
362.117
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| CAS # |
2342606-49-7
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| PubChem CID |
138682250
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C=CC(C2ON=C(C=2)CC2C=CC(=CC=2)OC2=CC=CC(F)=N2)=C(N)N=1
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| InChi Key |
HSPXTNVHQPVEGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15FN4O2/c21-18-4-1-5-19(24-18)26-15-8-6-13(7-9-15)11-14-12-17(27-25-14)16-3-2-10-23-20(16)22/h1-10,12H,11H2,(H2,22,23)
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| Chemical Name |
3-[3-[[4-(6-fluoropyridin-2-yl)oxyphenyl]methyl]-1,2-oxazol-5-yl]pyridin-2-amine
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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 (~275.97 mM)
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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 | 2.7597 mL | 13.7984 mL | 27.5969 mL | |
| 5 mM | 0.5519 mL | 2.7597 mL | 5.5194 mL | |
| 10 mM | 0.2760 mL | 1.3798 mL | 2.7597 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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