Friday, March 27, 2015

Drugs in Clinical Pipeline: Guadecitabine

Guadecitabine [2'-deoxy-5-azacytidylyl-(3’-5')-2'-deoxy-Guanosine] is a dinucleotide antimetabolite of a Decitabine linked via phosphodiester bond to a guanosine, with potential antineoplastic activity. 

Following metabolic activation by phosphorylation and incorporation into DNA, Guadecitabine inhibits DNA methyltransferase, thereby causing genome-wide and non-specific hypomethylation and inducing cell cycle arrest at S-phase. This agent is resistant to cytidine deaminase, hence may result in gradual release of Decitabine both extra- and intracellularly, leading to more prolonged exposures to Decitabine.

Generic Name: Guadecitabine
Synonym: SGI-110
CAS Number: 929901-49-5
Chemical Name: 2'-deoxy-5-azacytidylyl-(3’-5')-2'-deoxy-Guanosine
Mechanism of Action: DNA Methyltransferase Inhibitor
Indication: Antineoplastic, Various Cancers
Development Stage: Phase I
Developer: Astex Pharmaceuticals

1. SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction. NCT02348489