Cited by 177Protein Kinase Regulation and GTPase SignalingRNA Interference and Gene DeliveryProtein Tyrosine Phosphatases

Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS

Ross, Sarah J., Revenko, Alexey S., Hanson, Lyndsey L., Ellston, Rebecca, Staniszewska, Anna, Whalley, Nicky, Pandey, Sanjay K., Revill, Mitchell +9 more·2017·Science Translational Medicine

Abstract

AZD4785 is a therapeutic antisense oligonucleotide targeting KRAS mRNA with promising preclinical antitumor activity and a favorable safety profile.

Integrity signals

Registry

Crossref · 10.1126/scitranslmed.aal5253

Cites

52 of 52 references verified0 citation errors · 0 not checkable

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  • Early anti-KRAS siRNAs such as AZD-4785 targeted all KRAS isoforms; however, the trial for AZD-4785 was discontinued.

    “Early anti-KRAS siRNAs such as AZD-4785 targeted all KRAS isoforms; however, the trial for AZD-4785 was discontinued [69].”
  • AZD4785 achieves KRAS mRNA downregulation without any delivery agent.

    “The advanced chemistry of AZD4785 allows it to achieve this without any delivery agent.564”
  • AZD4785 is a high-affinity constrained ethyl-modified antisense oligonucleotide that downregulates KRAS mRNA by complementing the KRAS mRNA sequence in vitro and in vivo.

    “Among them, AZD4785 (236) is a high-affinity constrained ethyl-modified ASO that has shown potential activity in downregulating KRAS mRNA by complementing the KRAS mRNA sequence both in vitro and in vivo.”
  • AZD4785 selectively and efficiently reduces the mRNA of KRAS in cells, thereby inhibiting downstream effector pathways and exerting antiproliferative effects in KRAS mutant cells.

    “A chemically modified ASO, AZD4785, selectively and efficiently reduces the mRNA of KRAS in cells, thereby inhibiting the downstream effector pathways and exerting antiproliferative effects in KRAS mutant cells [59].”
  • AZD4785 is a KRAS antisense oligonucleotide that targets the KRAS gene irrespective of its mutation status.

    “AZD4785 is a KRAS antisense oligonucleotide that targets the KRAS gene irrespective of its mutation status (43).”

    From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [43]

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Authors
Ross, S. J., Revenko, A. S., Hanson, L. L., Ellston, R., Staniszewska, A., Whalley, N., Pandey, S. K., Revill, M., Rooney, C., Buckett, L. K., Klein, S. K., Hudson, K., Monia, B. P., Zinda, M., Blakey, D. C., Lyne, P. D., & Macleod, A. R.
Affiliations
  • AstraZeneca (United Kingdom) (GB)
  • Ionis Pharmaceuticals (United States) (US)
  • AstraZeneca, Cambridge CB2 0AA, UK.
  • AstraZeneca (United States) (US)
Corresponding author
  • Ross, Sarah J.
  • Revenko, Alexey S.
  • Lyne, Paul D.
  • Macleod, A. Robert
Venue
Science Translational Medicine
Published
2017-06-14
Volume
9
Issue
394
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
OpenAlex
W2624920353
Cited by
177
References
52
Citations by year
2026: 8 · 2025: 11 · 2024: 13 · 2023: 30 · 2022: 25 · 2021: 32 · 2020: 17 · 2019: 19 · 2018: 16 · 2017: 6
FWCI
6.48
Type
journal article
Language
en
Open access
closed
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • AstraZeneca
  • Ionis Pharmaceuticals
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
KRAS, antisense oligonucleotides, anticancer activity, drug safety
MeSH terms
Animals, Carcinoma, Non-Small-Cell Lung, Disease Models, Animal, Humans, Lung Neoplasms, Mutation, Signal Transduction, Oligonucleotides, Antisense, ras Proteins, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Mice

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