Physicochemical Properties
| Molecular Formula | C20H23N3O4 |
| Exact Mass | 369.168 |
| CAS # | 1410809-36-7 |
| Related CAS # | ACHN-975 TFA;1410809-37-8 |
| PubChem CID | 71466517 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 0.3 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 27 |
| Complexity | 698 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | CC(C)([C@@H](C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC#C[C@@H]2C[C@H]2CO)N |
| InChi Key | GOCUUDXEOKIQRU-IXDOHACOSA-N |
| InChi Code | InChI=1S/C20H23N3O4/c1-20(2,21)17(19(26)23-27)22-18(25)14-9-7-13(8-10-14)5-3-4-6-15-11-16(15)12-24/h7-10,15-17,24,27H,11-12,21H2,1-2H3,(H,22,25)(H,23,26)/t15-,16+,17-/m1/s1 |
| Chemical Name | N-((S)-3-amino-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-(((1R,2R)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide |
| Synonyms | ACHN 975 ACHN975 ACHN-975 |
| 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 | ACHN-975 has an IC50 of 0.02 nM and is directed against Enterobacteriaceae[1]. MIC90 values for ACHN-975 against Enterobacter, Pa, and Ab are 1, 0.5, and >64 μg/mL, respectively [1]. With a minimum inhibitory concentration (MIC) of less than 2 μg/ml, ACHN-975 demonstrated efficacy against all tested isolates of Pseudomonas aeruginosa. In relation to Pseudomonas aeruginosa, its MIC50 and MIC90 are, respectively, 0.06 and 0.25 μg/ml[2]. Targeting six strains of Pseudomonas aeruginosa, ACHN-975's minimum inhibitory concentrations (MIC) against APAE1064, APAE1232, and APAE1064 isolates are 0.12, 0.06, and 0.06 μg/ml, respectively [2]. The first crucial step in the manufacture of lipid A is catalyzed by LpxC, a highly conserved protein in Gram-negative bacteria. Zinc-dependent metalloamidase UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase is the bacterial enzyme known as LpxC [1]. |
| ln Vivo | Throughout the first four hours of therapy, bacterial titers steadily decreased in all dosage groups in response to ACHN-975 (ip; 5-30 mg/kg; single dose). The results of the sampling indicated that, two hours after treatment with the 10 mg/kg dose and four hours after treatment with the 30 mg/kg dose, the free drug levels in this model fell below the ACHN-975 MIC (0.25 μg/ml) for this isolate[2]. |
| Animal Protocol |
Animal/Disease Models: Pseudomonas aeruginosa ATCC 27853[2] Neutropenic mouse thigh model Doses: 5-30 mg/kg Route of Administration: intraperitonealadministration; single dose Experimental Results: bactericidal activity, anti-aeruginosa in vivo Pseudomonas sp. ATCC 27853 strain. |
| References |
[1]. Kalinin DV, et al. Insights into the Zinc-Dependent Deacetylase LpxC: Biochemical Properties and Inhibitor Design. Curr Top Med Chem. 2016;16(21):2379-430. [2]. Krause KM,et al. Potent LpxC Inhibitors with In Vitro Activity against Multidrug-Resistant Pseudomonas aeruginosa.Antimicrob Agents Chemother. 2019 Oct 22;63(11). pii: e00977-19. |
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.) |