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SCR7

Catalog No.GC12106

DNA ligase IV inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

SCR7 Chemical Structure

Cas No.: 1533426-72-0

Size Price Stock Qty
10mM (in 1mL DMSO)
$70.00
In stock
5mg
$65.00
In stock
25mg
$195.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Epithelial (A549) and melanoma (MelJuSo) cell line derivatives

Preparation method

Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

24 hours at 37°C

Applications

Scr7 increases the efficiency of insertional mutagenesis in cell lines. In A549 cells, 0.01 μM Scr7 improves the efficiency of insertion at the target site about threefold relative to the untreated control. In Scr7-treated MelJuSo cells, the insertion efficiency is also enhanced in a dose-dependent manner up to 19-fold.

Animal experiment [1]:

Animal models

Kell-LPETG mice

Dosage form

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. The injected zygotes were transferred at the 2-cell stage into the pseudo-pregnant females.

Applications

Co-injection of Scr7 increases the efficiency of precise genome editing in mouse embryos. The insertion efficiency with Scr7 co-injection is significantly higher (P = 0.0012) compared to blastocysts not injected with Scr7. The insertion efficiency in Scr7-co-injected E10 embryos is also significantly enhanced compared to E10 embryos not injected with Scr7 (P = 0.003).

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Maruyama T, Dougan SK, Truttmann MC et al. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 May;33(5):538-42.

Background

Scr7 is a DNA ligase IV inhibitor, initially identified as an anti-cancer agent [1].
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. Cells were treated with doxycycline to induce Cas9 expression, with various concentrations of Scr7 for 24 h. Scr7 maintained cells capable of entering S/G2 phase, which is necessary for HDR. [1] Treatment of mice with Scr7 affects lymphocyte development, as DNA ligase IV plays a key role in the joining of coding ends during V(D)J recombination by means of C-NHEJ16. The defects in lymphocyte development upon Scr7 treatment are transient and reversible, due to the noncovalent mode of binding of Scr7. Scr7 enhanced the frequency of HDR by transiently blocking NHEJ (with the exception of DNA ligase I–dependent alt-NHEJ), resulting in precise genome editing by CRISPR-Cas9 in both cultured cells and in mice. [2]
References:
[1]. Srivastava M, Nambiar M, Sharma S 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. doi: 10.1016/j.cell.2012.11.054.
[2]. Maruyama T, Dougan SK, Truttmann MC et al.Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 Mar 23. doi: 10.1038/nbt.3190. [Epub ahead of print]

Chemical Properties

Cas No. 1533426-72-0 SDF
Chemical Name 5,6-bis((E)-benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
Canonical SMILES S=C(NC(/N=C/C1=CC=CC=C1)=C2/N=C/C3=CC=CC=C3)NC2=O
Formula C18H14N4OS M.Wt 334.39
Solubility ≥ 16.7195mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.9905 mL 14.9526 mL 29.9052 mL
5 mM 0.5981 mL 2.9905 mL 5.981 mL
10 mM 0.2991 mL 1.4953 mL 2.9905 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 9 reference(s) in Google Scholar.)

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