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5-formyl-2'-deoxycytidine
- Development stage
- Preclinical
- Lead developer
- Ludwig Maximilian University of Munich
- Modality
- Small Molecules
- Administration
- Intravenous, Intraperitoneal, Oral, Topical, Rectal, Intrathecal, Intramuscular, Subcutaneous, Intranasal, Inhalation, Vaginal, Intratumoral, Parenteral, Transdermal
01
Overview
5-Formyl-2'-deoxycytidine (5fdC, often misspelled as 5'-formyl-2'-deoxycytidine) is a naturally occurring, epigenetically modified pyrimidine nucleoside. It is formed in genomic DNA via the iterative oxidation of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) by the Ten-Eleven Translocation (TET) family of dioxygenases, serving as a key intermediate in the active DNA demethylation pathway. In addition to its role as an epigenetic biomarker and research tool, 5fdC is being investigated as a selective therapeutic agent for cancers that overexpress cytidine deaminase (CDA), such as pancreatic cancer, non-small cell lung cancer (NSCLC) with ALK inhibitor resistance, and cytarabine-resistant myeloid leukemia. In these cells, CDA deaminates 5fdC into 5-formyl-2'-deoxyuridine (5fdU), which is subsequently phosphorylated and incorporated into genomic DNA, leading to lethal DNA damage, cell cycle arrest, and apoptosis. Furthermore, DNA sequences containing 5fdC can form covalent complexes with DNA methyltransferases (DNMTs), potentially inhibiting their activity.
- Other names
- 5-CHO-dC5-formyl-2'-deoxycytidine5-formyl-dC5'-formyl-2'-deoxycytidine5fdCfdC
02
Targets
CDA (Cytidine deaminase)TET1 (Methylcytosine dioxygenase TET1)DDR (DNA damage response)TET2 (Methylcytosine dioxygenase TET2)DNMT1 (DNA (cytosine-5)-methyltransferase 1)DNATET3 (Tet methylcytosine dioxygenase 3)
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