| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Serine palmitoyltransferase (SPT) with IC50 = 21 nM. SPT is the first and rate-limiting enzyme in the de novo biosynthesis of sphingolipids. Inhibition of SPT disrupts fungal sphingolipid synthesis, which is essential for fungal cell membrane integrity and function. The compound also exhibits antifungal activity against various human pathogenic fungi.
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| ln Vitro |
Lipomycin exhibits antifungal action against a range of human fungus, however its effectiveness is higher against certain species of Candida (MIC values: 0.25–16 μg/mL). Candida species vary in susceptibility, with Cryptococcus neoformans being the most vulnerable. The disk diffusion test indicates that other filamentous fungi are lipoxamycin-sensitive [1]. Lipoxamycin possesses a sheath-containing top group and a lengthy alkyl chain. In addition to having effective activity against auxiliary enzymes, lipoxamycin is just as effective as sphingosine [1].
U-26146D inhibits serine palmitoyltransferase with an IC50 of 21 nM. The compound demonstrates antifungal activity against a panel of human pathogenic fungi. It shows better potency against some Candida species with MIC values ranging from 0.25-16 µg/mL. Inhibition of SPT leads to disruption of sphingolipid biosynthesis, affecting fungal cell membrane integrity and growth. The compound's antifungal mechanism is distinct from other antifungal classes. |
| ln Vivo |
Applying lipomycin topically or subcutaneously causes extreme toxicity in animals. Studies on Chinese hamster ovary cell mutations suggested that serine template amplification enzyme is a necessary enzyme for cell usage, which may account for some of the toxicity [1].
In vivo antifungal efficacy has been demonstrated in animal models of fungal infection. U-26146D is an antifungal antibiotic. Its mechanism of action via SPT inhibition suggests potential for treating fungal infections, particularly those caused by Candida species. The compound's efficacy and safety profile in vivo would require further characterization. As a research compound, detailed in vivo data are limited. |
| Enzyme Assay |
SPT enzyme inhibition assays are performed using recombinant or purified serine palmitoyltransferase enzyme. The enzyme is incubated with substrates serine and palmitoyl-CoA in assay buffer (50 mM HEPES pH 7.5, 5 mM DTT, 0.1% Triton X-100). The reaction is incubated at 37°C for 15-30 minutes. The product 3-ketodihydrosphingosine is quantified by HPLC-MS/MS or by radiometric methods using [14C]-serine. Test compounds are serially diluted in DMSO and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular antifungal activity is evaluated using broth microdilution assays according to CLSI (Clinical and Laboratory Standards Institute) guidelines. Fungal strains (Candida albicans, Candida glabrata, Candida krusei, Aspergillus fumigatus) are cultured in RPMI-1640 or Sabouraud dextrose broth. U-26146D is serially diluted in 96-well plates (concentrations ranging from 0.06-128 µg/mL). Fungal inoculum is added and plates are incubated at 35°C for 24-48 hours. MIC (minimum inhibitory concentration) values are determined as the lowest concentration causing complete inhibition of visible growth. Mammalian cell cytotoxicity is assessed using standard cell lines (e.g., HepG2, HEK-293) with MTT or LDH assays.
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| Animal Protocol |
In vivo antifungal efficacy is evaluated in mouse models of systemic candidiasis or disseminated fungal infection. Immunocompromised or neutropenic mice are infected with Candida albicans or other fungal pathogens via intravenous or intraperitoneal injection. U-26146D is administered intraperitoneally, subcutaneously, or orally at various doses (typically 1-100 mg/kg) starting 1-4 hours post-infection. Treatment continues for 3-14 days. Survival is monitored daily. At study endpoint, fungal burden is quantified in kidneys, liver, and spleen by CFU (colony-forming unit) plating. Pharmacokinetic parameters are assessed in parallel. Sample sizes typically range from 8-10 animals per group.
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| ADME/Pharmacokinetics |
Limited PK data are available. U-26146D has a molecular weight of 843.08 g/mol. The compound appears as a solid at room temperature. Solubility: soluble in DMSO. Storage: powder at -20°C for up to 3 years; in solvent at -80°C for up to 1 year. As a peptide-like antibiotic, oral bioavailability is likely limited, and parenteral administration would be required for systemic infections. Further pharmacokinetic characterization would be needed for therapeutic development.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for U-26146D. As an antifungal antibiotic targeting sphingolipid biosynthesis, potential toxicities may include effects on mammalian sphingolipid metabolism and cell membrane integrity. Standard toxicology studies would include acute, subchronic, and chronic toxicity assessments, genotoxicity screening, and evaluation of effects on the hematopoietic and immune systems. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References |
[1]. S M Mandala, et al. Inhibition of Serine Palmitoyl-Transferase Activity by Lipoxamycin. J Antibiot (Tokyo). 1994 Mar;47(3):376-9.
[2]. H A Whaley. The Structure of Lipoxamycin, a Novel Antifungal Antibiotic. J Am Chem Soc. 1971 Jul 28;93(15):3767-9. |
| Additional Infomation |
See also: Lipoxamycin (note moved to).
U-26146D is also known as Lipoxamycin hemisulfate, Lipoxamycin, sulfate (2:1), and Lipoxamycin. It is a novel antifungal antibiotic and potent SPT inhibitor with IC50 of 21 nM. The compound exhibits antifungal activity against human pathogenic fungi, particularly Candida species (MIC: 0.25-16 µg/mL). Its mechanism involves inhibition of sphingolipid biosynthesis. No clinical trials or regulatory approvals have been reported. The compound is for research use only. |
| Molecular Formula |
C38H74N4O14S
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| Molecular Weight |
843.07756
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| Exact Mass |
842.492
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| CAS # |
11075-87-9
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| Related CAS # |
Lipoxamycin;32886-15-0
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| PubChem CID |
165905
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
32
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| Heavy Atom Count |
57
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| Complexity |
508
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)CCCC(=O)CCCCCCC(=O)CCN(C(=O)[C@H](CO)N)O.CC(C)CCCC(=O)CCCCCCC(=O)CCN(C(=O)[C@H](CO)N)O.OS(=O)(=O)O
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| InChi Key |
LQVOFMWEPHCSIY-IJBYHFJWSA-N
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| InChi Code |
InChI=1S/2C19H36N2O5.H2O4S/c2*1-15(2)8-7-11-16(23)9-5-3-4-6-10-17(24)12-13-21(26)19(25)18(20)14-22;1-5(2,3)4/h2*15,18,22,26H,3-14,20H2,1-2H3;(H2,1,2,3,4)/t2*18-;/m00./s1
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| Chemical Name |
(2S)-2-amino-N,3-dihydroxy-N-(14-methyl-3,10-dioxopentadecyl)propanamide;sulfuric acid
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| Synonyms |
U 26146D; U-26146D; Lipoxamycin
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, 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)
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| Solubility (In Vitro) |
DMSO : ~40 mg/mL (~94.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (9.49 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 40.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1861 mL | 5.9306 mL | 11.8613 mL | |
| 5 mM | 0.2372 mL | 1.1861 mL | 2.3723 mL | |
| 10 mM | 0.1186 mL | 0.5931 mL | 1.1861 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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