| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
AN7973 targets fungal leucyl-tRNA synthetase, an enzyme essential for protein synthesis. By inhibiting this enzyme, the compound disrupts cellular function and leads to fungal cell death. The compound also blocks intracellular parasite development and inhibits Cryptosporidium parvum growth. This dual mechanism makes AN7973 a promising agent for treating cryptosporidiosis and other parasitic infections.
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| ln Vitro |
AN7973 demonstrates potent in vitro activity against Cryptosporidium and various fungal pathogens. It blocks intracellular parasite development and inhibits Cryptosporidium growth. The compound shows activity against Candida and Aspergillus species. AN7973's mechanism of action involves inhibition of leucyl-tRNA synthetase. The compound exhibits good in vitro potency and selectivity.
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| ln Vivo |
In mouse models of acute and chronic infection, AN7973 (oral gavage; 5–25 mg/kg; once daily) effectively eradicates C. the body's parvum [1]. In a neonatal calf model of cryptosporidiosis (as seen in infants), AN7973 (oral gavage; 5 mg/kg, 10 mg/kg, 6.67 mg/kg; once daily, twice daily, three times daily) decreases diarrhea, dehydration, and excretion of Cryptosporidium parvum [1]. With its promising safety, stability, and PK characteristics, AN7973 is a promising option for the treatment of cryptosporidiosis [1].
In vivo, AN7973 is orally active with favorable safety, stability, and PK parameters. Oral administration at 5-25 mg/kg once daily effectively treats both acute and chronic Cryptosporidium infections. The compound is an exciting drug candidate for treating cryptosporidiosis. AN7973 shows good oral bioavailability and tissue distribution. Efficacy has been demonstrated in animal models of cryptosporidiosis. |
| Enzyme Assay |
In vitro enzyme assays for AN7973 typically involve measuring inhibition of leucyl-tRNA synthetase activity from target organisms. Enzyme activity is assessed by monitoring aminoacylation of tRNA with leucine in the presence of varying concentrations of AN7973. IC50 values are determined from dose-response curves. Parasite growth inhibition assays using Cryptosporidium parvum or other relevant organisms assess antiparasitic activity. Fungal susceptibility testing follows CLSI guidelines.
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| Cell Assay |
Cellular assays for AN7973 involve treating Cryptosporidium-infected cell cultures or fungal cultures with varying concentrations of the compound (typically 0.01-100 microM range) for 24-72 hours. Parasite or fungal growth is assessed by microscopy, qPCR, or metabolic activity assays. Intracellular parasite development is monitored. Cytotoxicity against host cells is evaluated to determine selectivity. IC50 values are determined from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: NOD scid gamma mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (NSG)[1] chronically infected with Cryptosporidium for 4 to 5 weeks
Doses: 10 mg/kg, 20 mg/kg Route of Administration: oral Oral administration; 10 mg/kg, 20 mg/kg; one time/day. Experimental Results: Parasite shedding was diminished by >99% at the 25 mg/kg dose, and by >90% at the 10 mg/kg dose. Animal/Disease Models: fourweeks old female C57BL/6 IFN-γ−/− acute Cryptosporidium infection mice [1] Doses: 5 mg/kg, 10 mg/kg, 25 mg/kg Route of Administration: po (oral gavage); 5 mg/kg, 10 mg/kg, 25 mg/kg; single dairy Experimental Results: Elimination of Candida parvum with dose-dependent efficacy. Animal/Disease Models: 1-day to 2-day-old Holstein bull cryptosporidiosis neonatal calf model [1] Doses: 5 mg/kg, 10 mg/kg, 6.67 mg/kg Route of Administration: po (oral gavage); 5 mg /kg, 10 mg/kg, 6.67 mg/kg; one time/day, twice a day, three times a day Experimental Results: diminished parasite shedding and complete elimination of diarrhea. In vivo animal studies for AN7973 typically employ mouse models of cryptosporidiosis or fungal infection. Infected animals are administered AN7973 via oral gavage at doses ranging from 5-25 mg/kg once daily. Treatment efficacy is assessed by measuring parasite or fungal burden in tissues, clinical signs, and survival. Both acute and chronic infection models are used. Pharmacodynamic studies assess target engagement and biomarker modulation. |
| ADME/Pharmacokinetics |
AN7973 possesses favorable pharmacokinetic properties. It is orally active with good bioavailability. The compound shows good stability and favorable PK parameters. Following oral administration, appropriate plasma concentrations are achieved for therapeutic efficacy. PK parameters including half-life, Cmax, Tmax, and AUC are determined via LC-MS/MS analysis. The compound's favorable PK profile supports once-daily dosing.
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| Toxicity/Toxicokinetics |
AN7973 has a favorable safety profile. Preclinical studies indicate good tolerability at therapeutic doses. The compound shows favorable safety, stability, and PK parameters. As a research compound, standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies would be required for clinical development. The compound is for research use only.
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| References |
[1]. 1. Lunde CS, et al. Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis. Nat Commun. 2019 Jun 27; 10(1):2816.
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| Additional Infomation |
AN7973 (CAS# 1620899-32-2) is a 6-carboxamide benzoxaborole that blocks intracellular parasite development and inhibits Cryptosporidium growth. It is orally active with favorable safety, stability, and PK parameters. AN7973 is an exciting drug candidate for treating cryptosporidiosis. The compound targets fungal leucyl-tRNA synthetase. It is not approved for clinical use and is intended for research purposes. The compound is typically stored at -20degC.
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| Molecular Formula |
C19H17BCLN3O3
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| Molecular Weight |
381.620583295822
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| Exact Mass |
381.105
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| CAS # |
1620899-32-2
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| PubChem CID |
77846210
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
566
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| Defined Atom Stereocenter Count |
0
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| SMILES |
B1(C2=C(C=CC(=C2)NC(=O)C3=C(C=C(C=C3)N4C=CC=N4)Cl)C(O1)(C)C)O
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| InChi Key |
JUSVAUWJLCQPHI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17BClN3O3/c1-19(2)15-7-4-12(10-16(15)20(26)27-19)23-18(25)14-6-5-13(11-17(14)21)24-9-3-8-22-24/h3-11,26H,1-2H3,(H,23,25)
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| Chemical Name |
2-chloro-N-(1-hydroxy-3,3-dimethyl-2,1-benzoxaborol-6-yl)-4-pyrazol-1-ylbenzamide
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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 : ~125 mg/mL (~327.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 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: ≥ 2.08 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6204 mL | 13.1020 mL | 26.2041 mL | |
| 5 mM | 0.5241 mL | 2.6204 mL | 5.2408 mL | |
| 10 mM | 0.2620 mL | 1.3102 mL | 2.6204 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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