14892-97-8 Usage
Uses
SCR7 pyrazine has been used as a non-homologous end joining (NHEJ) modulator to study its effect on CRISPR/Cas9-mediated editing.
General Description
SCR7 pyrazine is an inhibitor of DNA ligase IV.
Biological Activity
scr7 pyrazine is an inhibitor of dna ligase iv [1].dna ligase iv is involved in sealing of double-strand breaks (dsbs) during nonhomologous end-joining (nhej). dsbs have been considered as one of the most lethal types of dna damage within cells. unrepaired dsbs may lead to chromosomal rearrangements such as translocations and deletions, resulting in oncogenic transformations or cell death. in higher eukaryotes, nhej is one of the primary mechanisms of dsb repair and is active throughout the cell cycle. nhej plays a major role in providing resistance to cancer cells to these radio- and chemotherapy agents [1].scr7 blocked ligase iv-mediated joining by interfering with its dna binding in cell-free repair system. scr7 inhibited nhej in a ligase iv-dependent manner within cells, and activated the intrinsic apoptotic pathway. scr7 dose-dependent decreased cell proliferation in mcf7, a549, and hela cells with an ic50 of 40, 34, and 44 μm, respectively. in t47d, a2780, and ht1080 cells, the ic50 values were 8.5, 120, and 10 μm, respectively [1].scr7 treatment (10 mg/kg, six doses) significantly reduced breast adenocarcinoma-induced tumor and impeded tumor progression in mouse models in mouse models. coadministered of scr7 with dsb-inducing therapeutic modalities significantly enhanced their sensitivity.
Biochem/physiol Actions
SCR7 pyrazine is reported to be an inhibitor of non-homologous end joining (NHEJ) and has been shown to enhance the efficiency of CRISPR-Cas9 genome editing. The effect of SCR7 pyrazine on the efficiency and targeting precision of CRISPR applications has been shown to be cell type specific and context dependent. SCR7 pyrazine is a product of spontaneous cyclization of SCR7, first reported by Srivastava, M., et al.
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[j]. cell, 2012, 151(7): 1474-1487.
Check Digit Verification of cas no
The CAS Registry Mumber 14892-97-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,4,8,9 and 2 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 14892-97:
(7*1)+(6*4)+(5*8)+(4*9)+(3*2)+(2*9)+(1*7)=138
138 % 10 = 8
So 14892-97-8 is a valid CAS Registry Number.
14892-97-8Relevant articles and documents
Synthesis and structure determination of SCR7, a DNA ligase inhibitor
Greco, George E.,Conrad, Zane A.,Johnston, Alycia M.,Li, Qingyao,Tomkinson, Alan E.
, p. 3204 - 3207 (2016)
In contrast to a published report, reaction of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine with 2?equiv of aromatic aldehydes produces a mixture of 6,7-diaryl-2-thioxopteridine-4-one and 6,7-diaryl-2-thioxo-7,8-dihydropteridine-4-one rather than a diimine. These compounds represent the correct structure for SCR7, a substance reported to be an inhibitor of nonhomologous end-joining, a DNA repair pathway. The dihydropteridine can be isolated as a minor product, and it can be oxidized to the pteridine.
NOVEL NUCLEIC ACID MODIFIERS
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Sheet 7, (2019/07/20)
The present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.
