Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

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Fig. 2. Effects of AZD4785 on proliferation and MAPK pathway signaling in KRAS mutant and wild-type cancer cells in vitro. Effects of AZD4785 on proliferation.

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Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

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Presentation transcript:

Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. (A) Sequence and binding region of AZD4785 to the 3′UTR of KRAS mRNA transcript. ds, unmodified bases; ks, cEt-modified bases; mC, 5-methylcytosine; ORF, open reading frame. (B) Relative expression of RAS mRNA isoforms measured by qRT-PCR in A431 cells after 72 hours of treatment with AZD4785 or CTRL ASO. Expression was normalized to ACTIN and shown relative to phosphate-buffered saline (PBS). Representative data from a minimum of two independent experiments are shown. (C) Western blot analysis of RAS and vinculin protein in A431 cells after 72 hours of treatment with CTRL ASO or AZD4785. (D) Mice bearing A431 tumors were treated with PBS or with 16, 32, or 48 mpk of AZD4785 5× weekly for 3 weeks. RAS isoform expression was measured in tumors at the end of the study by qRT-PCR. Expression was normalized to ACTIN and shown relative to PBS. The graph shows individual tumor data, treatment group mean, and SE. mpk/w, mpk/week. (E) IHC analysis of KRAS protein expression in A431 tumors after AZD4785 treatment. Scale bars, 200 μm. Sarah J. Ross et al., Sci Transl Med 2017;9:eaal5253 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.