product name SCR7
Description: SCR7 is a specific DNA Ligase IV inhibitor, which blocks nonhomologous end-joining (NHEJ) and was initially identified as an anti-cancer agent. Scr7 targets the DNA binding domain of DNA ligase IV, reducing its affinity for double strand breaks (DSBs) and inhibiting its function. Scr7 also inhibits DNA ligase III (but not DNA ligase I), albeit less efficiently.
References: Cell. 2012 Dec 21;151(7):1474-87; Nat Biotechnol. 2015 May;33(5):543-8.
332.38
Formula
C18H12N4OS
CAS No.
14892-97-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 66 mg/mL (198.6 mM)
Water: <1 mg/mL
Ethanol: 3 mg/mL (9.0 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19411774
| In Vitro |
In vitro activity: SCR7 effectively inhibits the formation of multimers at 200 μM and above. SCR7 successfully inhibits cell proliferation of MCF7, A549, HeLa, T47D, A2780, HT1080, and Nalm6 with IC50 of 40, 34, 44, 8.5, 120, 10, and 50 μM, respectively. SCR7 suppresses the NHEJ repair of CRISPR-Cas9-induced DSBs. Kinase Assay: Complementation experiment is carried out by adding increasing concentrations of purified Ligase IV/XRCC4 complex (30, 60, and 120 fmol) along with the oligomeric DNA substrates (5’ compatible and 5’-5’ noncompatible ends) to the SCR7-treatedextracts. Reactions are incubated for 2 h at 25℃. The reaction products are then resolved on 8% denaturing PAGE. The gel is dried and exposed and the signal is detected with a PhosphorImager and analyzed with Multi Gauge (V3.0) software. Cell Assay: Cell proliferation of cancer cells are determined by MTT and trypan blue assays. Briefly, MCF7, CEM, HeLa, A549, HT1080, A2780, T47D, Nalm6, N114 and K562 cells are grown in presence of SCR7 (10, 50, 100, and 250 μM) for 24 or 48 h, and subjected to MTT or trypan blue assays. Each experiment is repeated a minimum of three independent times. |
|---|---|
| In Vivo | SCR7 treatment (10 mg/kg, i.m.) significantly reduces breast adenocarcinoma-induced tumor, and exhibits 4-fold increase in lifespan compared with control group. However, in Swiss albino mice with Dalton’s lymphoma tumor model, SCR7 (20 mg/kg, i.p.) exhibits neither tumor regression nor increase in lifespan. In BALB/c mice, SCR7 (20 mg/kg, i.p.) significantly enhances the cytotoxic effects of radiation, etoposide and 3-Aminobenzamide on tumor derived from Dalton’s lymphoma (DLA) cells. |
| Animal model | Kell-LPETG mice |
| Formulation & Dosage | CRISPR components mixture (Cas9 mRNA, sgRNA and targeting template) and 10 mM of Scr7 NHEJ inhibitor (to 1 mM final) were injected into the cytoplasm at the pronuclear stage. |
| References | Cell. 2012 Dec 21;151(7):1474-87; Nat Biotechnol. 2015 May;33(5):543-8. |
