oralprodrughaving stearyl group joined tophosphoric acidat 5′ position ofarabinosemoiety of Ara-C. The mode of action is the inhibition of DNA synthesis after transformation to Ara-CTP as in cytosinearabinoside(Ara-C). In the liver, the drug is metabolized, yielding the intermediate metabolite,...
In support of this proposed mode of action of the HU + AZT combination is our finding that upon exposure of Cytarabine-resistant cells to AZT, they displayed decreased nuclear levels of monoubiquitylation of Ɣ-H2AX, which is necessary for elicitation of the DNA damage response, hence ...
Its clinical utility, however, is severely limited by its short plasma half-life because of the catabolic action of nucleoside deaminases.In this study, N(4)-carbamate derivatives of cytarabine (1) were synthesized and evaluated for transdermal penetration because this mode of administration may ...
Incorporation of 5-Aza-2'-deoxycytidine-5'-triphosphate into DNA. Interactions with mammalian DNA polymerase alpha and DNA methylase. In order to understand further the molecular mode of action of (5-AZA-dCyd), a potent antileukemic agent, we prepared enzymatically 5'-(5-AZA-dCTP) and perfor...
Cytarabine (AraC) is an essential chemotherapeutic for acute myeloid leukemia (AML) and resistance to this drug is a major cause of treatment failure. AraC is a nucleoside analog that differs from 2′-deoxycytidine only by the presence of an additional h
The upregulation of Mcl-1 is often a primary mode of both acquired and intrinsic resistance to therapy with venetoclax13,56. However, the baseline features that make patients less likely to respond to venetoclax-based regimens are not completely understood. Recently, it has been shown that AML ...
The ionspray voltage was set at 3000 V for negative mode and 4000 V for positive mode at a temperature of 350 ◦C and an auxiliary gas pressure of 15 psi. Quantification was performed using multiple reactions monitoring (MRM) as previously published [28]. Data acquisition was performed ...