Physicochemical Properties
| Molecular Formula | C9H11BCLNO4 |
| Molecular Weight | 243.451941728592 |
| Exact Mass | 243.046 |
| CAS # | 1853176-89-2 |
| PubChem CID | 140793266 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 16 |
| Complexity | 254 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | B1(C2=C(C=CC3=C2OCO3)[C@H](O1)CN)O.Cl |
| InChi Key | FYHCZFHPLJMBAX-OGFXRTJISA-N |
| InChi Code | InChI=1S/C9H10BNO4.ClH/c11-3-7-5-1-2-6-9(14-4-13-6)8(5)10(12)15-7;/h1-2,7,12H,3-4,11H2;1H/t7-;/m1./s1 |
| Chemical Name | [(3S)-1-hydroxy-3H-[1,3]dioxolo[4,5-g][2,1]benzoxaborol-3-yl]methanamine;hydrochloride |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | At MICs ranging from 0.25 to 2 μg/ml, DS86760016 inhibits a few Gram-negative bacteria. DS86760016 has a minimum inhibitory concentration (MIC) of greater than 32 μg/ml against Gram-positive bacteria. With a MIC90 of 2 μg/ml, DS86760016 is effective against all strains of K. pneumoniae, E. coli, and P. aeruginosa, including susceptible strains[1]. |
| ln Vivo | The drug DS86760016 exhibits considerable spontaneous resistance (FSR) for seven days (7.5-220 mg/kg; sc; q6h)[1]. The intravenous (IV) pharmacokinetic (PK) characteristics of DS86760016 are tested in mouse, rat, monkey, and dog plasma. In mouse, rat, monkey, and dog plasma, DS86760016 exhibits reduced intravenous plasma clearances (CLp) of 11, 29, 5.6, and 4.5 ml/min/kg, respectively. In mice, rats, monkeys, and dogs, the plasma half-lives (t1/2) of DS86760016 are 1.9, 1.5, 8.6, and 8.3 hours, respectively. Due to the reduced plasma clearance, there were higher plasma exposures for DS86760016 in mice, rats, monkeys, and dogs, with dose-normalized areas under the curve after intravenous administration (DNAUCIVs) of 1.5, 0.6, 3.7, and 3.0 μg h kg/ml/mg, respectively[1]. |
| Animal Protocol |
Animal/Disease Models: Immunocompetent female Swiss Webster mice (urinary tract infection, UTI model)[1] Doses: 7.5, 30, 220 mg/kg Route of Administration: Sc; q6h for 7 days Experimental Results: Bacteria resistant to DS86760016 were detected in a few animals after 1 day of treatment at doses of 7.5 and 30 mg/kg q6h; however, no resistant bacteria were detected at these doses after 7 days of treatment. No resistance was observed in any of the mice treated at a dose of 220 mg/kg q6h. |
| References |
[1]. Purnapatre KP, et al. In Vitro and In Vivo Activities of DS86760016, a Novel Leucyl-tRNA Synthetase Inhibitor for Gram-Negative Pathogens. Antimicrob Agents Chemother. 2018;62(4):e01987-17. Published 2018 Mar 27. [2]. Kumar M, et al. DS86760016, a Leucyl-tRNA Synthetase Inhibitor with Activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2019;63(4):e02122-18. Published 2019 Mar 27. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1076 mL | 20.5381 mL | 41.0762 mL | |
| 5 mM | 0.8215 mL | 4.1076 mL | 8.2152 mL | |
| 10 mM | 0.4108 mL | 2.0538 mL | 4.1076 mL |