 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C22H21N4NAO9S2 |
| Molecular Weight | 554.53 (Anhydrous) |
| Exact Mass | 572.064 |
| Elemental Analysis | C, 46.15; H, 3.70; N, 9.79; Na, 4.02; O, 25.15; S, 11.20 |
| CAS # | 1426397-23-0 |
| Related CAS # | Cefsulodin sodium;52152-93-9 |
| PubChem CID | 134128779 |
| Appearance | Solid powder |
| LogP | 0.1 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 38 |
| Complexity | 1040 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | S1C([H])([H])C(C([H])([H])[N+]2C([H])=C([H])C(/C(=N/[H])/[O-])=C([H])C=2[H])=C(C(=O)O[H])N2C([C@@]([H])([C@@]12[H])N([H])C([C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])S(=O)(=O)[O-])=O)=O.[Na+].O([H])[H] |
| InChi Key | XTRRFIYXAPRYES-NLFZDHTNSA-M |
| InChi Code | InChI=1S/C22H20N4O8S2.Na.H2O/c23-18(27)13-6-8-25(9-7-13)10-14-11-35-21-15(20(29)26(21)16(14)22(30)31)24-19(28)17(36(32,33)34)12-4-2-1-3-5-12;;/h1-9,15,17,21H,10-11H2,(H4-,23,24,27,28,30,31,32,33,34);;1H2/q;+1;/p-1/t15-,17-,21-;;/m1../s1 |
| Chemical Name | sodium (6R,7R)-3-((4-carbamoylpyridin-1-ium-1-yl)methyl)-8-oxo-7-((R)-2-phenyl-2-sulfonatoacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrate |
| Synonyms | SCE-129 sodium hydrate; SCE129 sodium hydrate |
| 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
| Targets | Bacterial cell wall synthesis; penicillin binding protein (PBP) |
| ln Vitro | In comparison to carbenicillin (HY-B0525), cefsulodin sodium (0.5-64 mg/mL; 18 h) exhibits a 16–32 fold increase in activity against Psuedomonas aeruginosa at minimum inhibitory concentrations (MICs) of 0.5–64 mg/mL [1]. When P. aeruginosa grows in the presence of benzylpenicillin, it produces beta-lactamase, which does not hydrolyze cefsulodin sodium (8–16 μg/mL; 4.5 h)[1]. |
| ln Vivo | Cefsulodin sodium (1 g/kg/tag; ip; 5 d, 9 single doses with intervals of 12 h) exhibits tubule toxic threshold doses of 250 mg /kg (sc; 12 d) with nine single doses, as well as a rising excretion of tubule cells in the rat as a measure of nephrotoxicity[4]. |
| Enzyme Assay | Cefsulodin sodium (SCE-129, CGP-7174/E), active in minimum inhibitory concentrations (MICs) of 0.5 to 64 microgram/ml, was about 16- to 32-fold more active than carbenicillin against Psuedomonas aeruginosa. It was also active against P. diminuta, P. maltophilia, P. paucimobilis, and P. pseudoalcaligenes (MICs of 1 to 32 microgram/ml) but not against other species of Pseudomonas or other gram-negative bacteria. Except with highly carbenicillin-resistant isolates, MICs of cefsulodin for P. aeruginosa were little affected by an increase in the inoculum. With a small inoculum, minimum bactericidal concentrations (MBCs) were the same as or twice the MIC, but increasing the inoculum had a greater effect on the MBC than on the MIC. Cefsulodin was not hydrolyzed by the beta-lactamase induced in P. aeruginosa by growth in the presence of benzylpenicillin and was a poor substrate for beta-lactamases from Enterobacter cloacae and Proteus morganii. However, it was hydrolyzed, albeit slowly, by the beta-lactamase produced by most of our highly carbenicillin-resistant isolates of P. aeruginosa and by TEM-type beta-lactamases [2]. |
| Cell Assay | mPTPB is a virulent phosphatase from Mycobacterium tuberculosis and a promising therapeutic target for tuberculosis. To facilitate mPTPB-based drug discovery, we identified α-sulfophenylacetic amide (SPAA) from cefsulodin, a third generation β-lactam cephalosporin antibiotic, as a novel pTyr pharmacophore for mPTPB. Structure-guided and fragment-based optimization of SPAA led to the most potent and selective mPTPB inhibitor 9, with a K i of 7.9 nM and more than 10,000-fold preference for mPTPB over a large panel of 25 phosphatases. Compound 9 also exhibited excellent cellular activity and specificity in blocking mPTPB function in macrophage. Given its novel structure, modest molecular mass, and extremely high ligand efficiency (0.46), compound 9 represents an outstanding lead compound for anti-TB drug discovery targeting mPTPB [1]. |
| References |
[1]. In vitro antibacterial activity and susceptibility of cefsulodin, an antipseudomonal cephalosporin, to beta-lactamases. Antimicrob Agents Chemother. 1980 Feb;17(2):165-9. [2]. Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23. [3]. Cefsulodin Inspired Potent and Selective Inhibitors of mPTPB, a Virulent Phosphatase from Mycobacterium tuberculosis. ACS Med Chem Lett. 2015 Nov 3;6(12):1231-5. [4]. Renal tolerance of imipenem/cilastatin and other beta-lactam antibiotics in rats. Infection. 1985;13 Suppl 1:S156-60. |
Solubility Data
| Solubility (In Vitro) | DMSO: > 10 mM |
| 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.) |