Physicochemical Properties
| Molecular Formula | C51H51N13O12S6 |
| Molecular Weight | 1230.4 |
| Exact Mass | 1221.147 |
| Elemental Analysis | C, 49.79; H, 4.18; N, 14.80; O, 15.60; S, 15.63 |
| CAS # | 56377-79-8 |
| Related CAS # | 56377-79-8; |
| PubChem CID | 16129696 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.5±0.1 g/cm3 |
| Melting Point | 310-320° (dec) |
| Index of Refraction | 1.699 |
| LogP | 0.72 |
| Hydrogen Bond Donor Count | 10 |
| Hydrogen Bond Acceptor Count | 24 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 82 |
| Complexity | 2510 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | NC(C(NC(C1=CSC(C2C(O)=CC3C4SC=C(C(NC(C(N/C(/C5SC=C(C(NC6CC(O)C(=O)OCC7=C8C(NC(=C8C)C(=O)SCC(C8SC=C(C=3N=2)N=8)NC(=O)C2=CSC6=N2)=CC=C7)=O)N=5)=C\C)=O)C(O)C)=O)N=4)=N1)=O)=C)=O |
| InChi Key | OQAOHXRUMXWDLQ-ATVZKCIHSA-N |
| InChi Code | 1S/C51H43N13O12S6/c1-5-23-46-60-28(14-79-46)41(70)56-25-10-33(67)50(74)76-11-21-7-6-8-24-34(21)18(2)35(54-24)51(75)82-17-31(57-42(71)29-15-80-47(25)61-29)48-58-26(12-78-48)37-22(45-59-30(13-77-45)43(72)64-36(20(4)65)44(73)55-23)9-32(66)38(63-37)49-62-27(16-81-49)40(69)53-19(3)39(52)68/h5-9,12-16,20,25,31,33,36,54,65-67H,3,10-11,17H2,1-2,4H3,(H2,52,68)(H,53,69)(H,55,73)(H,56,70)(H,57,71)(H,64,72)/b23-5-/t20-,25+,31+,33+,36+/m1/s1 |
| Chemical Name | A name could not be generated for this structure. |
| Synonyms | Nosiheptide; Multhiomycin; Multiomycin; Nosiheptidum; RP 9671; RP-9671; RP9671; |
| 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 | Nosiheptide demonstrated substantial efficacy against all modern S. MIC values ≤ 0.25 mg/L were found for several drug-resistant clinical isolates among the tested aureus strains. Nosiheptide was inert against the majority of tested Gram-negative germs, however it was quite active against Enterococcus species and modern, highly virulent Clostridium difficile BI strains. Nosiheptide was able to rapidly kill Staphylococcus aureus in a concentration- and time-dependent manner, achieving over 2 log killing rates at 10X MIC in under 6 hours, according to time-kill study. Moreover, it was discovered that nosiheptide's anti-S and noncytotoxic at >> 100X MIC to mammalian cells. Twenty percent human serum did not inhibit aureus activity. Notably, nosiheptide showed considerably longer post-antibiotic effects than vancomycin did against Staphylococcus aureus linked to healthcare and the community [1]. |
| ln Vivo | In female CD1 mice, nosiheptide (20 mg/kg; i.p.; 1 and 8 h postinfection) dramatically reduced mortality. Six out of ten mice in the control group perished on day one, whereas ten mice receiving nosiheptide were still alive on day three [1]. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old female CD1 mice were injected with HA-Staphylococcus aureus strain Sanger 252[1]. Doses: 20 mg/kg. Route of Administration: intraperitoneal (ip) injection; intraperitoneal (ip) injection. Injection results at 1 hour and 8 hrs (hrs (hours)) after infection: Provided significant protection against death. |
| References |
[1]. Activity of the thiopeptide antibiotic nosiheptide against contemporary strains of methicillin-resistant Staphylococcus aureus. J Antibiot (Tokyo). 2012 Dec;65(12):593-8. [2]. Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework. ACS Chem Biol. 2009 Oct 16;4(10):855-64. |
| Additional Infomation |
Nosiheptide has been reported in Streptomyces actuosus and Streptomyces griseosporeus with data available. See also: Nosiheptide (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~81.81 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8127 mL | 4.0637 mL | 8.1274 mL | |
| 5 mM | 0.1625 mL | 0.8127 mL | 1.6255 mL | |
| 10 mM | 0.0813 mL | 0.4064 mL | 0.8127 mL |