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Mecillinam (FL-1060; amdinocillin) is a potent and broad spectrum penicillin antibiotic that binds specifically to penicillin binding protein 2 (PBP2), and is only considered to be active against Gram-negative bacteria. It is used primarily in the treatment of urinary tract infections, and has also been used to treat typhoid and paratyphoid fever. Because mecillinam has very low orally bioavailable bioavailability, an orally bioavailable prodrug pivmecillinam. Neither drug is available in the United States.
Physicochemical Properties
| Exact Mass | 439.214 |
| Elemental Analysis | C, 55.36; H, 7.12; N, 12.91; O, 14.75; S, 9.85 |
| CAS # | 32887-01-7 |
| Related CAS # | Mecillinam-d12 |
| PubChem CID | 36273 |
| Appearance | Solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 581.0±60.0 °C at 760 mmHg |
| Melting Point | 156°C |
| Flash Point | 305.2±32.9 °C |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.604 |
| LogP | 2.97 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 22 |
| Complexity | 500 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)N=CN3CCCCCC3)C(=O)O)C |
| InChi Key | BWWVAEOLVKTZFQ-CXUHLZMHSA-N |
| InChi Code | InChI=1S/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/b16-9+ |
| Chemical Name | (2S,5R,6R)-6-(azepan-1-ylmethylideneamino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid |
| Synonyms | Mecillinam FL 1060 AMDINOCILLIN FL-1060Coactin Penicillin HX Mecillinamum Hexacillin FL1060 |
| 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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
| Targets | β-lactam |
| ln Vivo | Treatment of catheter-associated infections can be achieved with high dosages (400 mg per kg of body weight/d) of mecillinam (Amdinocillin, 400 mg per kg)[1]. |
| Animal Protocol |
Animal Model: High dosages (400 mg per kg of body weight/d) of mecillinam (Amdinocillin, 400 mg per kg) are effective in treating catheter-associated infections[1]. Dosage: 50, 100, 200, and 400 mg per kg. Administration: Intravenously each day in four divided doses over a 72-h period. Result: High dose of 400 mg/kg exhibited significant activity. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Poorly absorbed if given orally. Biological Half-Life Approximately 1 hour in patients with normal renal function. Increases to 3 to 6 hours in anephric patients. |
| References |
[1]Amdinocillin Treatment of Catheter-Associated Bacteriuria in Rabbits. J Infect Dis. 1989 Jun;159(6):1065-72.; [2] Amdinocillin (Mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob Agents Chemother. 2015 Mar;59(3):1718-27. |
| Additional Infomation |
Mecillinam is a penicillin in which the 6beta substituent is [(azepan-1-yl)methylidene]amino; an extended-spectrum penicillin antibiotic that binds specifically to penicillin binding protein 2 (PBP2), and is only considered to be active against Gram-negative bacteria. It has a role as an antibacterial drug and an antiinfective agent. Amidinopenicillanic acid derivative with broad spectrum antibacterial action. It is poorly absorbed if given orally and is used in urinary infections and typhus. Amdinocillin is not available in the United States. Amdinocillin is a semisynthetic, broad spectrum beta-lactam penicillin with antibacterial activity. Amdinocillin specifically binds to and inactivates penicillin-binding protein 2 (PBP 2) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall and causes cell lysis. Given the fact that most beta-lactam penicillins bind almost exclusively to PBPs 1 and 3, amdinocillin is able to synergize with other penicillins in the treatment against bacterial infections. An amidinopenicillanic acid derivative with broad spectrum antibacterial action. See also: Amdinocillin Pivoxil (has salt form). Drug Indication Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms. Mechanism of Action Amdinocillin is a stong and specific antagonist of Penicillin Binding Protein-2 (PBP 2). It is active against gram negative bacteria, preventing cell wall synthesis by inhibiting the activity of PBP2. PBP2 is a peptidoglycan elongation initiating enzyme. Peptidoglycan is a polymer of sugars and amino acids that is the main component of bacterial cell walls. Pharmacodynamics Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Co-administration of probenecid results in markedly elevated plasma levels of amdinocillin and delays its excretion. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 65~250 mg/mL (199.73 ~768.21 mM) H2O : ~100 mg/mL (~307.29 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (19.21 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 62.5 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: ≥ 6.25 mg/mL (19.21 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 62.5 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. Solubility in Formulation 3: ≥ 6.25 mg/mL (19.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (307.29 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |