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aza-TdCyd
- Development stage
- Unknown
- Lead developer
- Nanopharmaceutics
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
aza-TdCyd (5-aza-4'-thio-2'-deoxycytidine) is an orally bioavailable, second-generation nucleoside analog and a potent inhibitor of DNA methyltransferase 1 (DNMT1). Developed by Nanopharmaceutics (TRON Group) in collaboration with the National Cancer Institute (NCI), it is designed to address the limitations of first-generation DNMT inhibitors like decitabine and azacitidine, offering improved aqueous stability and a longer half-life. The drug acts by incorporating into the DNA of rapidly dividing cells, where it forms a covalent complex with DNMT1, triggering the enzyme's proteasomal degradation. This depletion leads to global DNA hypomethylation, which can reactivate silenced tumor suppressor genes and induce cell cycle arrest or apoptosis. It is currently in Phase 1 clinical development for the treatment of advanced solid tumors.
- Other names
- 5-aza-4'-thio-2'-deoxycytidine5-aza-T-dCyd
02
Targets
DNMT1 (DNA (cytosine-5)-methyltransferase 1)DNMT3B (DNA (cytosine-5)-methyltransferase 3B)
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