SCR7 inhibits end joining of double strand breaks in diverse cell types resulting in tumour regression by activation of p53 mediated apoptosis.SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when coadministered with DSB-inducing therapeutic modalities enhances their sensitivity significantly.SCR7 is a new anti cancer molecule having capability to selectively inhibit non-homologous end joining (NHEJ), one of the DNA double strand break (DSB) repair pathways inside the cells.
|Source||Blood (2016). Figure 2. SCR7|
|Cell Lines||MM cell lines|
|Incubation Time||0-120 hours|
|Results||Thus, increased apoptosis and cytotoxicity as well as decreased cell viability were observed in RPMI 8226 compared with LR5 cells, especially 72 hours post melphalan treatment.Again, in both cell lines, increased sensitivity towardmelphalanwas observed in the presence of the inhibitors; SCR7 showed the strongest effect.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Pluronic copolymer encapsulated SCR7 as a potential anticancer agent.
John F, et al. Faraday Discuss. 2015;177:155-61. PMID: 25608025.
Enhanced efficacy of pluronic copolymer micelle encapsulated SCR7 against cancer cell proliferation.
John F, et al. Macromol Biosci. 2015 Apr;15(4):521-34. PMID: 25515310.
An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression.
Srivastava M, et al. Cell. 2012 Dec 21;151(7):1474-87. PMID: 23260137.
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