Synonym
NU7441; NU-7441; NU 7441; KU-57788; KU 57788; KU57788
IUPAC/Chemical Name
8-(4-dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one
InChi Key
JAMULYFATHSZJM-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H19NO3S/c27-21-15-23(26-11-13-28-14-12-26)29-24-17(6-3-9-20(21)24)19-8-4-7-18-16-5-1-2-10-22(16)30-25(18)19/h1-10,15H,11-14H2
SMILES Code
O=C1C=C(N2CCOCC2)OC3=C(C4=C5C(C6=CC=CC=C6S5)=CC=C4)C=CC=C13
Appearance
Off-white to beige solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly.
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
KU-57788 (NU7441) is a DNA-PK inhibitor with an IC50 of 14 nM.
In vitro activity:
The effect of NU7441 on the growth of liver cancer HepG2 cells treated with different doses of NU7441, from 0.5 to 10 µM was investigated (Fig. 1). NU7441 had an inhibitory effect on cell growth, indicating the potential application of this medicine to kill the cancer cells. Moreover, this inhibition was dose- and time-dependent, with a maximal inhibitory effect for 72 h at a dosage of 10 µM NU7441.
Reference: Cell Physiol Biochem. 2016;38(5):1897-905. https://www.karger.com/Article/FullText/445551
In vivo activity:
Mice bearing SW620 tumor xenografts were treated with etoposide phosphate alone and in combination with NU7441 ( Fig. 5B). Tumors in control mice reached four times their starting volume (RTV4) at a median time of 5.6 days (i.e., time to RTV4 = 5.6 days). Treatment with etoposide phosphate alone caused a tumor growth delay of 2.7 days (time to RTV4 = 8.3 days), which was extended to 5.4 days (time to RTV4 = 11 days, P = 0.0159 compared with etoposide alone) by coadministration of NU7441. Thus, NU7441 enhanced etoposide phosphate efficacy by 100%.
Reference: Cancer Res. 2006 May 15;66(10):5354-62. https://cancerres.aacrjournals.org/content/66/10/5354.long
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
14.0 |
33.90 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
413.49
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Yang C, Wang Q, Liu X, Cheng X, Jiang X, Zhang Y, Feng Z, Zhou P. NU7441 Enhances the Radiosensitivity of Liver Cancer Cells. Cell Physiol Biochem. 2016;38(5):1897-905. doi: 10.1159/000445551. Epub 2016 May 9. PMID: 27160694.
2. Zhao Y, Thomas HD, Batey MA, Cowell IG, Richardson CJ, Griffin RJ, Calvert AH, Newell DR, Smith GC, Curtin NJ. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 2006 May 15;66(10):5354-62. doi: 10.1158/0008-5472.CAN-05-4275. PMID: 16707462.
In vitro protocol:
1. Yang C, Wang Q, Liu X, Cheng X, Jiang X, Zhang Y, Feng Z, Zhou P. NU7441 Enhances the Radiosensitivity of Liver Cancer Cells. Cell Physiol Biochem. 2016;38(5):1897-905. doi: 10.1159/000445551. Epub 2016 May 9. PMID: 27160694.
In vivo protocol:
1. Zhao Y, Thomas HD, Batey MA, Cowell IG, Richardson CJ, Griffin RJ, Calvert AH, Newell DR, Smith GC, Curtin NJ. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 2006 May 15;66(10):5354-62. doi: 10.1158/0008-5472.CAN-05-4275. PMID: 16707462.
1: Tichy A, Durisova K, Salovska B, Pejchal J, Zarybnicka L, Vavrova J, Dye NA, Sinkorova Z. Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441. Radiat Environ Biophys. 2013 Oct 8. [Epub ahead of print] PubMed PMID: 24100951.
2: Tavecchio M, Munck JM, Cano C, Newell DR, Curtin NJ. Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination. Cancer Chemother Pharmacol. 2012 Jan;69(1):155-64. doi: 10.1007/s00280-011-1662-4. Epub 2011 Jun 1. PubMed PMID: 21630086.
3: Zhao Y, Thomas HD, Batey MA, Cowell IG, Richardson CJ, Griffin RJ, Calvert AH, Newell DR, Smith GC, Curtin NJ. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 2006 May 15;66(10):5354-62. PubMed PMID: 16707462.
4: Leahy JJ, Golding BT, Griffin RJ, Hardcastle IR, Richardson C, Rigoreau L, Smith GC. Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7. PubMed PMID: 15546735.
