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azd4785
- Development stage
- Discontinued
- Lead developer
- AstraZeneca
- Modality
- Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Intravenous
01
Overview
AZD4785 is a high-affinity, next-generation antisense oligonucleotide (ASO) designed to target and downregulate KRAS mRNA, thereby reducing KRAS protein expression. It incorporates constrained ethyl (cEt) modifications for enhanced potency and selectivity. By binding to the 3′ untranslated region of KRAS mRNA, AZD4785 induces RNase H1-mediated degradation of the transcript, leading to inhibition of downstream Ras effector pathways and antiproliferative effects in KRAS-mutant cells. Preclinical studies demonstrated potent antitumor activity in models of non-small cell lung cancer (NSCLC) and other solid tumors driven by mutant KRAS, with favorable safety profiles observed in animal models. The drug was developed primarily for advanced solid tumors where KRAS is an important driver of tumor survival[1][2][4][6].
- Other names
- KRAS antisense oligonucleotideKRAS ASO
02
Targets
Kirsten rat sarcoma viral oncogene homolog mRNAKRAS (Kirsten rat sarcoma viral oncogene homolog)
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