NU7026

NU7026 is a novel specific DNA-PK inhibitor with IC50 of 0.23±0.01 μM, also inhibits PI3K with IC50 of 13±3 μM.

Product information

CAS Number: 154447-35-5

Molecular Weight: 281.31

Formula: C17H15NO3

Chemical Name: 2-morpholino-4H-benzo[h]chromen-4-one

Smiles: O=C1C=C(OC2=C1C=CC1=CC=CC=C12)N1CCOCC1

InChiKey: KKTZALUTXUZPSN-UHFFFAOYSA-N

InChi: InChI=1S/C17H15NO3/c19-15-11-16(18-7-9-20-10-8-18)21-17-13-4-2-1-3-12(13)5-6-14(15)17/h1-6,11H,7-10H2

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 2.8 mg/mL (Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

NU7026 (10 μM) potentiates ionizing radiation (IR) cytotoxicity [potentiation factor at 90% cell kill (PF90)=1.51±0.04] in exponentially growing DNA-PK proficient but not deficient cells. NU7026 synergistically sensitizes I83 cells to Chlorambucil (CLB) 3.5-fold.NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 μM, 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.

In Vivo:

NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Following intravenous administration to mice at 5 mg/kg, NU7026 underwent rapid plasma clearance (0.108 L/h) and this is largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg/kg is 20 and 15%, respectively.

References:

1. Tu Y, Yang B, Ji C, Yang Z, Gu H, Lu CC, Wang R, Su ZL, Chen B, Sun WL, Xia JP, Bi ZG, He L. DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SIN1 association mediates ultraviolet B (UVB)-induced Akt Ser-473 phosphorylation and skin cell survival. Mol Cancer. 2013 Dec 24;12(1):172. [Epub ahead of print] PubMed PMID: 24365180.
2. 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.
3. Chiang JH, Yang JS, Lu CC, Hour MJ, Liu KC, Lin JH, Lee TH, Chung JG. Effect of DNA damage response by quinazolinone analogue HMJ-38 on human umbilical vein endothelial cells: Evidence for γH2A.X and DNA-PK-dependent pathway. Hum Exp Toxicol. 2013 Sep 23. [Epub ahead of print] PubMed PMID: 24064905.
4. Zhou X, Zhang X, Xie Y, Tanaka K, Wang B, Zhang H. DNA-PKcs inhibition sensitizes cancer cells to carbon-ion irradiation via telomere capping disruption. PLoS One. 2013 Aug 27;8(8):e72641. doi: 10.1371/journal.pone.0072641. PubMed PMID: 24013362; PubMed Central PMCID: PMC3754927.

Products are for research use only. Not for human use.