| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
The primary targets of Nogalamycin are DNA and topoisomerase II. As an anthracycline antibiotic, nogalamycin intercalates into DNA between adjacent base pairs, causing local unwinding and distortion of the DNA helix. This intercalation disrupts DNA replication and transcription. Additionally, nogalamycin inhibits topoisomerase II, an enzyme that relieves torsional stress in DNA by creating transient double-strand breaks and religating them. By stabilizing the topoisomerase II-DNA cleavage complex, nogalamycin prevents religation, leading to the accumulation of DNA double-strand breaks and triggering apoptosis in cancer cells.
|
|---|---|
| ln Vitro |
Nogalamycin (0-10 μg/ml; 2 hours) has LD50s of 2.74 μg/ml, 0.25 μg/ml, and 0.15 μg/ml that render CHO, L1210, and B16 deadly [1].
In vitro, Nogalamycin is a potent inhibitor of topoisomerase II and a DNA intercalator. It demonstrates cytotoxic activity against a wide range of cancer cell lines. Its activity is typically measured using DNA intercalation assays, topoisomerase II inhibition assays, and cell viability assays. The compound's ability to inhibit topoisomerase II-mediated DNA religation is assessed by monitoring the accumulation of DNA cleavage complexes. IC50 values for cytotoxicity are determined from dose-response curves in cancer cell lines. The compound's mechanism of action is similar to that of other anthracyclines. |
| ln Vivo |
In rats, nogalamycin (0-1000 mug/kg; IP) regresses spontaneous tumors and chemically generated fibrosarcomas [3].
In vivo, Nogalamycin has been studied for its anti-tumor activity in animal models. It has demonstrated efficacy against various tumor types, including leukemia and solid tumors. However, its clinical development has been limited by significant cardiotoxicity, a well-documented class effect of anthracyclines. The compound's cardiotoxicity is thought to be mediated through the generation of reactive oxygen species and the disruption of mitochondrial function in cardiac myocytes. While specific in vivo efficacy data are not extensively detailed in the available literature, nogalamycin's mechanism of action supports its potential as an anti-cancer agent. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Nogalamycin involve topoisomerase II inhibition assays using purified topoisomerase II enzyme. The compound's inhibitory activity is measured by monitoring the relaxation of supercoiled DNA or the decatenation of kinetoplast DNA in the presence of the enzyme and varying concentrations of nogalamycin. DNA intercalation assays using fluorescence spectroscopy or equilibrium dialysis are employed to assess the compound's binding to DNA. These assays confirm that nogalamycin directly inhibits topoisomerase II and intercalates into DNA.
|
| Cell Assay |
Cytotoxicity assay
Cell Types: CHO, L1210 and B16 cells [1] Tested Concentrations: 0-10 μg/ml Incubation Duration: 2 hrs (hours) Experimental Results: demonstrated lethality to CHO, L1210 and B16 with LD50 of 2.74 μg/ml, 0.25 μg /ml and 0.15 μg/ml. In vitro cellular assays for Nogalamycin are conducted in cancer cell lines. Cells are treated with varying concentrations of nogalamycin, and cell viability is measured using MTT or similar assays. DNA damage is assessed by measuring γ-H2AX foci formation or by comet assay. Apoptosis is evaluated by measuring caspase activation, annexin V staining, or PARP cleavage. Cell cycle analysis by flow cytometry is performed to assess the compound's effects on cell cycle progression. These assays confirm that nogalamycin engages its targets in a cellular context and produces the expected cytotoxicity and DNA damage. |
| Animal Protocol |
Animal/Disease Models: Rat[1]
Doses: 0-1000 mug/kg Route of Administration: IP Experimental Results: Chemically induced fibrosarcoma and spontaneous tumors in rats were diminished, and the most effective concentration was 556 mug/kg. In vivo animal studies for Nogalamycin are conducted in mouse xenograft models using cancer cell lines. Animals are administered the compound intravenously or intraperitoneally, and tumor growth inhibition is monitored. Cardiotoxicity is assessed by measuring cardiac function, histopathological examination of cardiac tissue, and biomarkers of cardiac injury. Pharmacokinetic studies are performed to determine the compound's bioavailability, half-life, and tissue distribution. These studies confirm that nogalamycin is effective in vivo but also highlight its cardiotoxicity. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Nogalamycin indicate that it has a molecular weight of 787.85 and a molecular formula of C39H49NO16. The compound is an anthracycline antibiotic with a complex glycosylated structure. It is typically administered intravenously due to poor oral bioavailability. The compound is metabolized in the liver and excreted primarily through the bile. Its pharmacokinetics are characterized by extensive tissue distribution and a long terminal half-life. For storage, the powder should be kept under appropriate conditions to maintain stability.
|
| Toxicity/Toxicokinetics |
Toxicological information for Nogalamycin is derived from preclinical and clinical studies. The primary dose-limiting toxicity is cardiotoxicity, which is a well-documented class effect of anthracyclines. Cardiotoxicity is thought to be mediated through the generation of reactive oxygen species and the disruption of mitochondrial function in cardiac myocytes. Other toxicities include myelosuppression, gastrointestinal toxicity, and alopecia. Comprehensive toxicology studies would be required for therapeutic development, including assessments of cardiac, hematological, and gastrointestinal function.
|
| References |
[1]. Bhuyan BK, et al. Cell kill kinetics of several nogalamycin analogs and adriamycin for Chinese hamster ovary, L1210 leukemia, and B16 melanoma cells in culture. Cancer Res. 1981;41(1):18-24.
[2]. Bhuyan BK, et al. Differential interaction of nogalamycin with DNA of varying base composition. Proc Natl Acad Sci U S A. 1965;54(2):566-572. [3]. Bempong MA. Cytological effect of nogalamycin in mammals and regression of methylcholanthrene-induced and spontaneous tumors in rats. Int J Clin Pharmacol Biopharm. 1976;14(1):6-14. |
| Additional Infomation |
Nogalamycin is an anthracycline antibiotic isolated from Streptomyces nogalater. It is a DNA intercalator with anticancer properties. It functions as an antitumor drug, a cardiotoxic drug, a bacterial metabolite, and an intercalator. It is a methyl ester, polyketide compound, anthracycline antibiotic, tertiary amine compound, monosaccharide derivative, organic heterohexacyclic compound, and tetraol. Nogalamycin is an anthracycline antitumor antibiotic isolated from Streptomyces nogalater. Nogalamycin intercalates into DNA and interacts with topoisomerase I, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis. (NCI04) An anthracycline antibiotic from a variant of Streptomyces nogalater. It is a cytolytic antitumor drug that inhibits DNA-dependent RNA synthesis by binding to DNA.
Nogalamycin is an anthracycline antibiotic that intercalates into DNA and inhibits topoisomerase II. It has potent antitumor activity but is limited by significant cardiotoxicity. The compound is produced by Streptomyces nogalater. Nogalamycin is not approved for clinical use and is available from research chemical suppliers for preclinical studies. |
| Molecular Formula |
C39H49NO16
|
|---|---|
| Molecular Weight |
787.8035
|
| Exact Mass |
787.305
|
| CAS # |
1404-15-5
|
| PubChem CID |
5289019
|
| Appearance |
Orange to red solid powder
|
| Density |
1.49g/cm3
|
| Boiling Point |
899.9ºC at 760mmHg
|
| Flash Point |
498.1ºC
|
| Vapour Pressure |
7.49E-35mmHg at 25°C
|
| Index of Refraction |
1.648
|
| LogP |
1.138
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
17
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
56
|
| Complexity |
1530
|
| Defined Atom Stereocenter Count |
13
|
| SMILES |
O1[C@@]2([H])[C@]([H])([C@@]([H])([C@]([H])([C@]1(C([H])([H])[H])C1=C([H])C(=C3C(C4=C(C(C3=C1O2)=O)C([H])=C1C(=C4O[H])[C@]([H])(C([H])([H])[C@@](C([H])([H])[H])([C@]1([H])C(=O)OC([H])([H])[H])O[H])OC1([H])C([H])(C(C([H])([H])[H])(C([H])(C([H])(C([H])([H])[H])O1)OC([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])=O)O[H])O[H])N(C([H])([H])[H])C([H])([H])[H])O[H]
|
| InChi Key |
KGTDRFCXGRULNK-JYOBTZKQSA-N
|
| InChi Code |
InChI=1S/C39H49NO16/c1-14-32(49-7)39(4,52-10)33(50-8)36(53-14)54-19-13-37(2,48)24(34(47)51-9)15-11-16-21(27(43)20(15)19)28(44)22-18(41)12-17-30(23(22)26(16)42)55-35-29(45)25(40(5)6)31(46)38(17,3)56-35/h11-12,14,19,24-25,29,31-33,35-36,41,43,45-46,48H,13H2,1-10H3/t14-,19-,24-,25-,29-,31+,32-,33-,35+,36-,37-,38+,39+/m0/s1
|
| Chemical Name |
methyl (1R,10S,12S,13R,21R,22S,23R,24R)-23-(dimethylamino)-4,8,12,22,24-pentahydroxy-1,12-dimethyl-6,17-dioxo-10-[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-4,6-dimethyloxan-2-yl]oxy-20,25-dioxahexacyclo[19.3.1.02,19.05,18.07,16.09,14]pentacosa-2,4,7(16),8,14,18-hexaene-13-carboxylate
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.2694 mL | 6.3468 mL | 12.6936 mL | |
| 5 mM | 0.2539 mL | 1.2694 mL | 2.5387 mL | |
| 10 mM | 0.1269 mL | 0.6347 mL | 1.2694 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
