product name NU7026
Description: NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, it is 60-fold more selective for DNA-PK than PI3K and inactive against both ATM and ATR. NU 7026 is often used in combination with PARP-1 inhibitor AG14361 to sensitize tumor cells to radio- or chemo-therapy. When tested with primary PARP-1-/- and cells PARP-1+/+ cells, NU 7026 treatment (<50 μM) sensitized cells to IR-induced cytotoxicity and reduced clonogenic survival by inhibiting DNA-PK.
References: Blood. 2004 Jun 15;103(12):4659-65; Br J Cancer. 2005 Oct 31;93(9):1011-8; Cancer Res. 2009 Mar 1;69(5):2100-7.
281.31
Formula
C17H15NO3
CAS No.
154447-35-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 1 mg/mL (3.55 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
LY293646
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19411115
| In Vitro |
In vitro activity: NU7026 potentiates ionizing radiation induced cytotoxicity in a concentration-dependent manner in V3YAC and PARP-1+/+ cells. NU7026 completely abolishes potentially lethal damage recovery in growth-arrested cells. NU7026 inhibits DNA DSB repair by 56% in the V3YAC cell line. NU7026 (10 μM) potentiates the growth inhibitory effects of idarubicin, daunorubicin, doxorubicin, etoposide, mAMSA, and mitoxantrone with PF50 values ranging from approximately 19 for mAMSA to approximately 2 for idarubicin in K562 cells. NU7026 (10 μM) also potentiates the growth inhibitory effect of etoposide in this leukemia cell line with a PF50 value of 10.53. NU7026 (10 μM) enhances the etoposide-induced cell cycle G2 blockade in K562 cells. NU7026 potentiates topo II poisons involves inhibition of nonhomologous end joining and a G2/M checkpoint arrest. NU7026 (10 μM) exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. NU7026 (< 10 μM) plus chlorambucil has synergistic cytotoxic activity at nontoxic doses of NU7026 in a CLL cell line (I83) and in primary CLL-lymphocytes. NU7026 (10 μM) increases chlorambucil-induced G(2)/M arrest in I83 cells. NU7026 (10 μM) enhances chlorambucil -induced γH2AX throughout the cell cycle in the I83 cell line. NU7026 (10 μM) Increases chlorambucil-Induced apoptosis in the I83 cell line. NU7026 (55 μM) results in a dramatic induction of telomere fusion in p53 null MEFs and significantly fewer telomere fusions in p53 and ligase IV double null MEFs Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | NU7026 (20mg/kg, i.v.) undergoes rapid plasma clearance (0.108/hour) in mice and this is largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration of NU7026 at dose of 20 mg/kg is 20 and 15%, respectively. |
| Animal model | Female BALB/c mice |
| Formulation & Dosage | Dissolved in 10% DMSO and 5% Tween 20 in saline; 25 mg/kg; i.p. injection or oral administration |
| References | Blood. 2004 Jun 15;103(12):4659-65; Br J Cancer. 2005 Oct 31;93(9):1011-8; Cancer Res. 2009 Mar 1;69(5):2100-7. |
