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lenalidomide oligonucleotide PROTAC
- Development stage
- Preclinical
- Lead developer
- Upstate Medical University
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, 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, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules, Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Oral, Buccal, Inhalation, Sublingual, Rectal, Vaginal, Intranasal, Transdermal, Parenteral, Intravenous, Intramuscular, Subcutaneous, Intradermal, Intraperitoneal, Intraarticular, Intrathecal, Implant, Intratumoral
01
Overview
lenalidomide oligonucleotide PROTAC is an experimental proteolysis-targeting chimera (PROTAC) designed to target and degrade Abelson Interactor 1 (ABI1), an adaptor protein and transcription regulator that drives metastasis in breast and prostate cancers. The PROTAC consists of an oligonucleotide (DNA) sequence that acts as a bait for the homeobox homology region (HHR) of ABI1, covalently linked via click chemistry to lenalidomide, which recruits the cereblon (CRBN) E3 ubiquitin ligase. By bringing ABI1 into proximity with the CRBN E3 ligase complex, the chimeric molecule induces the ubiquitination and subsequent proteasomal degradation of ABI1, thereby inhibiting cell migration, adhesion, and metastasis.
- Other names
- DNA-based PROTAC targeting ABI1
02
Targets
CRBN (Cereblon)IKZF1 (Ikaros family zinc finger protein 1)IKZF3 (Zinc finger protein Aiolos)
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