| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: =90.9%
| Targets |
DNA: Phleomycin is an anticancer glycopeptide antibiotic that causes DNA cleavage. The mechanism involves DNA degradation, leading to cell death. [1]
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| ln Vitro |
DNA Cleavage Activity: Phleomycin itself is not an efficient catalyst of plasmid DNA cleavage in the absence of added cofactors. However, in the presence of one-electron reductants such as dithiothreitol (DTT), glutathione (GSH), 2-mercaptoethanol, or ascorbic acid, it can induce both single-stranded and double-stranded DNA damage. The maximum rate of degradation of supercoiled plasmid DNA (pBR322) to its linear form (Form III) was observed with 1 mM ascorbic acid. [1]
Kinetics of DNA Cleavage: In the presence of 0.01 mM phleomycin and 1 mM ascorbic acid at pH 7.4, a time-dependent degradation of superhelical DNA (Form I) to nicked circular (Form II) and finally to linear DNA (Form III) was observed. The process suggests an accumulation of single-strand breaks leading to double-strand cleavage. [1] Reactive Oxygen Species (ROS) Generation: In the presence of cofactors (H₂O₂, ascorbic acid, glutathione, 2-mercaptoethanol, dithiothreitol), phleomycin generates reactive oxygen species, including hydroxyl radicals (•OH), which are responsible for DNA cleavage. DMSO (a •OH scavenger) and NaN₃ (a singlet oxygen scavenger) inhibited DNA cleavage, confirming the involvement of ROS. [1] Hydroxyl Radical Formation Rate: The pseudo-first order rate constants (kobs × 10⁻² [s⁻¹]) for NDMA (a hydroxyl radical scavenger) decomposition in the presence of 0.01 mM phleomycin and 1 mM cofactors at pH 7.4 and 37°C were determined: ascorbic acid (1.73), glutathione (2.26), 2-mercaptoethanol (2.52), and dithiothreitol (5.48). Dithiothreitol showed the highest rate of •OH generation, decomposing nearly 85% of NDMA after 60 minutes. [1] |
| ADME/Pharmacokinetics |
Metal Ion Coordination: Phleomycin naturally occurs and is commercially available as a copper(II) complex. The study provides a detailed characterization of the Cu(II) binding process. Potentiometric titrations revealed that phleomycin behaves as a hepta-protic acid (H₇L), releasing 7 protons. The acid dissociation constants (pKa) for various functional groups were determined: pyrimidine N (∼1.7), thiazole N (∼1.8), thiazoline N (∼2.7), imidazole N (6.38), α-NH₃⁺ of β-aminoalanine (7.12), and simultaneous dissociation of guanidine and amino group of 4-amino-5-methylpyrimidine (11.19, 11.20). [1]
Copper(II) Coordination Mode: The coordination of Cu(II) by phleomycin involves up to five nitrogen donor atoms. Four are in the equatorial plane: the pyrimidine ring nitrogen (N1), the secondary amine of β-aminoalanine (N2), the imidazole nitrogen (N3), and the amide nitrogen of the nearest peptide bond from β-hydroxyhistidine (N4). The fifth nitrogen, the α-amino group of β-aminoalanine (N5), is coordinated in the apical position, resulting in a square-pyramidal geometry. This coordination forms four thermodynamically stable chelate rings (three five-membered and one six-membered). [1] Copper(II) Complex Stability: The overall stability constants (log β) for various Cu(II)-phleomycin complex species (CuH₄L⁶⁺, CuH₃L⁵⁺, CuH₂L⁴⁺, CuHL³⁺, CuL²⁺, CuH₋₁L⁺, CuH₋₂L) were determined by potentiometry. The coordination sphere remains unchanged from CuHL³⁺ to CuH₋₂L, with only deprotonation of distant moieties (guanidine, amino group) and a coordinated water molecule occurring. [1] Structural Relationship: The copper binding site is relatively close to the DNA-interacting moiety of the molecule, supporting the hypothesis that the metal ion is important for the anticancer activity involving DNA degradation. [1] |
| References | |
| Additional Infomation |
Background: Phleomycin is a glycopeptide antibiotic and a member of the bleomycin family. It was first isolated from Streptomyces verticillus in 1956. It is a broad-spectrum antibiotic with anticancer activity based on DNA cleavage. Severe DNA damage leads to cell death. [1]
Structural Features: Phleomycin differs from bleomycin by having a thiazinylthiazole moiety instead of a bithiazole group. This structural change increases its solubility but does not impact the coordination mode with metal ions. It naturally occurs and is commercially available as a copper(II) complex. [1] Mechanism of Action: The anticancer mode of action is considered to be based on DNA cleavage in the presence of molecular oxygen and a one-electron reductant. The copper(II) ion is reduced to copper(I) by the reductant (e.g., ascorbic acid, thiols), leading to the generation of reactive oxygen species (ROS) via Fenton-like reactions. These ROS, particularly hydroxyl radicals, are responsible for oxidative DNA damage, causing single- and double-strand breaks. [1] Copper Removal for Studies: To study the ligand's properties without the metal, copper(II) ions must be removed. This was effectively achieved using Chelex® 100 chelating resin, confirmed by the disappearance of EPR signals. [1] |
| Molecular Formula |
C51H75N17O21S2
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|---|---|
| Molecular Weight |
418.44
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| Exact Mass |
1323.47
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| CAS # |
11006-33-0
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| PubChem CID |
21226163
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| Appearance |
Light blue to blue solid powder
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| Density |
1.83 g/cm3
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| Boiling Point |
1718.8ºC at 760 mmHg
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| Flash Point |
993.3ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.777
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| LogP |
-10.2
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| Hydrogen Bond Donor Count |
20
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| Hydrogen Bond Acceptor Count |
31
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| Rotatable Bond Count |
31
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| Heavy Atom Count |
91
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| Complexity |
2650
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QRBLKGHRWFGINE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C51H75N17O21S2/c1-16-29(65-41(68-38(16)54)21(8-27(53)72)60-9-20(52)39(55)78)44(82)67-31(34(22-10-58-15-61-22)88-49-50(5,36(76)33(74)25(11-69)87-49)89-47-37(77)51(85,48(57)84)35(75)26(12-70)86-47)45(83)62-18(3)32(73)17(2)42(80)66-30(19(4)71)43(81)59-7-6-28-63-24(14-90-28)46-64-23(13-91-46)40(56)79/h10,13,15,17-18,20-21,24-26,30-37,47,49,60,69-70,73-77,85H,6-9,11-12,14,52H2,1-5H3,(H2,53,72)(H2,55,78)(H2,56,79)(H2,57,84)(H,58,61)(H,59,81)(H,62,83)(H,66,80)(H,67,82)(H2,54,65,68)
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| Chemical Name |
2-[2-[2-[[2-[[4-[[2-[[6-amino-2-[3-amino-1-[(2,3-diamino-3-oxopropyl)amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[3-[4-carbamoyl-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)-3-methyloxan-2-yl]oxy-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxy-2-methylpentanoyl]amino]-3-oxobutanoyl]amino]ethyl]-4,5-dihydro-1,3-thiazol-4-yl]-1,3-thiazole-4-carboxamide
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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 (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)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3898 mL | 11.9491 mL | 23.8983 mL | |
| 5 mM | 0.4780 mL | 2.3898 mL | 4.7797 mL | |
| 10 mM | 0.2390 mL | 1.1949 mL | 2.3898 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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