Hypomethylating agents (HMAs) have played an important role in this group of patients but their efficacy is limited. Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation ...
RG108was developed by rational drug design to block the active sites of DNMTs with very little toxicity. Although antitumor effects in human prostate cancer cells (Graca et al., 2014) have been observed, the mechanism of action of this agent is unclear and additional studies of this compound ...
Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation inhibitor in development for the treatment of AML and MDS. Expert opinion: Although guadecitabine did not yield improved ...
Early clinical trials sustain the concept of epigenetic enhancement of immunotherapy [20, 21] yet the precise mechanism of action and the crucial cellular targets of epigenetic drugs remain unknown. Guadecitabine is a dinucleotide prodrug of a decitabine linked via phosphodiester bond to a guanosine. ...
Hypomethylating agents (HMAs) have played an important role in this group of patients but their efficacy is limited. Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation ...
CompoundType of MDSMechanism(s) of actionClinical trialDevelopment Guadecitabine (SGI-110)High riskSecond generation HMA, resistant to degradation by citidine deaminaseNCT01261312 NCT02131597 NCT02197676 NCT02907359 (vs tr. choices)Phase I/II
In further investigating the mechanism of cytoreduction by gDEC, a PCR array analyses of 84 chromatin modifying enzymes demonstrated upregulation of several lysine-specific methyltransferases (KMTs: KMT2A, KMT2C, KMT2E, KMT2H, KMT5A), confirmed by additional expression analyses in vitro and of ...