| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
DNA-PK
|
|---|---|
| ln Vitro |
In order to confirm the nature of M2 and M3, authentic samples of both NU7199 and NU7200 (Figure 1) were compared to the spectra of the pseudomolecular ions at m/z 300 in plasma and urine. Two peaks were detected at m/z 300 in both plasma and urine and retention times and product ion spectra indicated that M2 corresponds to NU7199 and M3 to NU7200 (data not shown).
Following re-extraction and quantitation (Table 2), it appeared that NU7199 was the most prevalent of the two metabolites (10% in both plasma and urine), thus suggesting that the main hydroxylation position is the 2 position of the morpholino ring. A general scheme of the metabolism of NU7026 is shown in Figure 6.[1]
|
| References |
[1]. Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer. 2005 Oct 31;93(9):1011-8.
|
| Additional Infomation |
In this study we investigated the in vitro time dependence of radiosensitisation, pharmacokinetics and metabolism of NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 muM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. Following intravenous administration to mice at 5 mg kg(-1), NU7026 underwent rapid plasma clearance (0.108 l h(-1)) and this was largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg kg(-1) was 20 and 15%, respectively. Investigation of NU7026 metabolism profiles in plasma and urine indicated that the compound undergoes multiple hydroxylations. A glucuronide conjugate of a bis-hydroxylated metabolite represented the major excretion product in urine. Identification of the major oxidation site as C-2 of the morpholine ring was confirmed by the fact that the plasma clearance of NU7107 (an analogue of NU7026 methylated at C-2 and C-6 of the morpholine ring) was four-fold slower than that of NU7026. The pharmacokinetic simulations performed predict that NU7026 will have to be administered four times per day at 100 mg kg(-1) i.p. in order to obtain the drug exposure required for radiosensitisation.[1]
|
| Molecular Formula |
C17H17NO4
|
|---|---|
| Molecular Weight |
299.32118
|
| Exact Mass |
299.115
|
| Elemental Analysis |
C, 68.21; H, 5.72; N, 4.68; O, 21.38
|
| CAS # |
69541-04-4
|
| PubChem CID |
59335361
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
522.3±50.0 °C at 760 mmHg
|
| Flash Point |
269.7±30.1 °C
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.692
|
| LogP |
3.19
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
22
|
| Complexity |
430
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C=C(OC2=C1C=CC3=CC=CC=C32)N(CCO)CCO
|
| InChi Key |
LWJFQWULMGFQKX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17NO4/c19-9-7-18(8-10-20)16-11-15(21)14-6-5-12-3-1-2-4-13(12)17(14)22-16/h1-6,11,19-20H,7-10H2
|
| Chemical Name |
2-[bis(2-hydroxyethyl)amino]benzo[h]chromen-4-one
|
| Synonyms |
NU7199; NU 7199; 2-[bis(2-hydroxyethyl)amino]benzo[h]chromen-4-one; SCHEMBL13346531; DTXSID70731551; 2-[Bis(2-hydroxyethyl)amino]-4H-naphtho[1,2-b]pyran-4-one; NU7199
|
| 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 | 3.3409 mL | 16.7045 mL | 33.4091 mL | |
| 5 mM | 0.6682 mL | 3.3409 mL | 6.6818 mL | |
| 10 mM | 0.3341 mL | 1.6705 mL | 3.3409 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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