Brief Description

SCR7 is a molecule that inhibits joining of DSBs in cell-free repair system; inhibits NHEJ in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway.
IC50 value: ~40 nM in Hela and A549 cell [1]
Target: Ligase IV inhibitor; NHEJ inhibitor
in vitro: SCR7 does not induce DSBs directly to the genome and is Ligase IV dependent. Besides, upon incubation of oligomeric dsDNA or supercoiled plasmid DNA with increasing concentrations of SCR7, there was no evidence for DNA breaks. Accumulation of DSBs leads to cell death upon SCR7 treatment with a dose-dependent decrease in cell proliferation of MCF7, A549, and HeLa with an IC50 of 40, 34, and 44 μM, respectively, which was further confirmed by DIC imaging in MCF7. T47D, A2780, and HT1080 were also sensitive to SCR7, with an IC50 of 8.5, 120, and 10 μM, respectively [1]. SCR7 encapsulated micelles (ES) were also characterized by small-angle neutron scattering (SANS). Encapsulated SCR7 treatment resulted in accumulation of DNA breaks within the cells, resulting in cell cycle arrest at G1 phase and activation of apoptosis [2].
in vivo: SCR7 treatment (10 mg/kg, six doses) significantly reduced breast adenocarcinoma-induced tumor in mice. Untreated tumor animals survived only for 52 days, whereas treated animals exhibited ～4-fold increase in lifespan. Treatment with SCR7 resulted in regression of tumors with no obvious adverse effects. In addition, HPLC analysis of serum following administration of SCR7 into mice (20 mg/kg) showed bioavailability of 114 μg/ml and a t1/2 of 1 hr [1].
References on SCR7:
[1]. Srivastava M, et al. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012 Dec 21;151(7):1474-87.
[2]. John F, et al. Enhanced Efficacy of Pluronic Copolymer Micelle Encapsulated SCR7 against Cancer Cell Proliferation. Macromol Biosci. 2014 Dec 16. doi: 10.1002/mabi.201400480.

Solubility

10 mM in DMSO

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light yellow to yellow solid