A-54556A
IC50: 0.2 μg/ml for Bacillus subtilis 168
A-54556A is a natural acyldepsipeptide (ADEP) antibiotic.
Acyldepsipeptides (ADEP), a new class of antibiotics, has antibacterial activity against Gram-positive bacteria. The acyldepsipeptides are active against isolates that are resistant to antibiotics, implying a new target identify as ClpP.
In vitro: Previous study found that the treatment of B. subtilis with 1.6 mg/ml of A-54556A reduced the number of viable cells by 2 log units. In addition, the biosynthesis of DNA, RNA, protein, cell wall and fatty acid proceeded unhindered for 1 h at 2 mg/ml A-54556A, whereas classical antibiotics were clearly distinguished by preferential inhibition of their target pathway. Microscopic examination showed that after addition of A-54556A at concentrations as low as 0.4 mg/ml, B. subtilis started to form filaments [1].
In vivo: Two A-54556A analogs, ADEP 2 and ADEP 4, were proven to be active in the treatment of bacterial infections in rodents. When mice were challenged with a lethal systemic infection of E. faecalis, 1 mg/kg ADEP 2 or 0.5 mg/kg ADEP 4 were sufficient for 100% survival. In lethal sepsis caused by S. aureus, 12.5 mg/kg ADEP 4 rescued 80% of the mice and reduced the bacterial loads in liver, spleen and lung by 2–3 log units compared to an untreated control [1].
Clinical trial: Up to now, A-54556A is still in the preclinical development stage.
Reference:
[1] H. Brtz-Oesterhelt, D. Beyer, H. P. Kroll, et al. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nature Medicine 11(10), 1082-1087 (2005).
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 718.9 |
| Cas No. | 95398-45-1 |
| Formula | C38H50N6O8 |
| Synonyms | ADEP 1,A-54556 Factor A |
| Solubility | Soluble in DMSO |
| Chemical Name | (4R)-(6→2)-lactone N-[(2E,4E,6E)-1-oxo-2,4,6-octatrien-1-yl]-L-phenylalanyl-L-seryl-L-prolyl-N-methyl-L-alanyl-L-alanyl-4-methyl-L-proline |
| SDF | Download SDF |
| Canonical SMILES | O=C([C@@H](NC(/C=C/C=C/C=C/C)=O)CC1=CC=CC=C1)N[C@@H](COC2=O)C(N3[C@H](C(N([C@@H](C)C(N[C@H](C(N4[C@H]2C[C@@H](C)C4)=O)C)=O)C)=O)CCC3)=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
B. subtilis |
|
Preparation method |
The solubility of this compound in DMSO is soluble. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
1.6 mg/ml |
|
Applications |
Previous studies have found that treating B. subtilis with 1.6 mg / ml of A-54556A reduced the number of living cells by 2 log units. When treated with 2 mg / ml A-54556A for one hour, the biosynthesis of DNA, RNA, proteins, cell walls, and fatty acids is not affected, while traditional antibiotics are significantly different by preferentially inhibiting their target pathways. |
| Animal experiment [1]: | |
|
Animal models |
Bacterially infected mice |
|
Dosage form |
1 mg/kg ADEP 2 or 0.5 mg/kg ADEP 4 |
|
Application |
The results show that two analogues of A-54556A, ADEP 2 and ADEP 4, are active in the treatment of rodent bacterial infections. When mice were challenged with E. faecalis infection and treated with 1 mg/kg ADEP 2 or 0.5 mg/kg ADEP 4, the mice survived 100%. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Brötz-Oesterhelt H, Beyer D, Kroll HP, Endermann R, Ladel C, Schroeder W, Hinzen B, Raddatz S, Paulsen H, Henninger K, Bandow JE, Sahl HG, Labischinski H. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.Nat Med. 2005 Oct;11(10):1082-7. Epub 2005 Oct 2. Erratum in: Nat Med. 2005 Dec;11(12):1361. PubMed PMID: 16200071. |
|
Quality Control & MSDS
- View current batch:
Chemical structure
