Cytarabine triphosphate (Ara-CTP), a competitive inhibitor of DNA synthesis and an active metabolite of Cytarabine, exhibits predictive potential for leukemic blasts' chemosensitivity to Cytarabine through intracellular levels.
Cytarabine 5′-monophosphate (ara-CMP), an active metabolite of the nucleoside analog cytarabine formed by deoxycytidine kinase, is incorporated into DNA by DNA polymerase α, significantly slowing DNA synthesis. It inhibits nuclear and mitochondrial DNA replication in S. cerevisiae at 15 mM and improves survival in an L1210 murine leukemia model at 3.5-75.1 mg kg.
MBC-11 triethylamine has potential to treat tumor-induced bone disease (TIBD), is a first-in-class conjugate of the bone-targeting bisphosphonate etidronate covalently linked to the antimetabolite cytarabine (araC).
Fazarabine, also known as Kymarabine, is an orally-active pyrimidine analogue of an aza-substituted cytidine in which the ribose moiety is replaced by an arabinose sugar. Similar in action to cytarabine, fazarabine is phosphorylated by deoxycytidine kinase to a triphosphate form which competes with thymidine for incorporation into DNA; its incorporation into DNA inhibits DNA synthesis, resulting in tumor cell death and tumor necrosis. The presence of deoxycytidine kinase in a tumor is a determinant of tumor sensitivity to this drug.
APcK110 is a novel Kit inhibitor . APcK110 inhibits proliferation of the mastocytosis cell line HMC1.2 and the SCF-responsive cell line OCI AML3 in a dose-dependent manner . APcK110 is a more potent inhibitor of OCI AML3 proliferation than the clinically used Kit inhibitors imatinib and dasatinib and at least as potent as cytarabine. APcK110 inhibits the phosphorylation of Kit, Stat3, Stat5, and Akt in a dose-dependent fashion, showing activity of APcK110 on Kit and its downstream signaling pathways . APcK110 may have potent application in AML.