Alovudine

Alovudine (3'-Fluoro-3'-deoxythymidine) is a mtDNA synthesis inhibitor and a marker of DNA synthesis. Alovudine is less susceptible to inflammatory changes than ¹⁸F-Fluorodeoxyglucose (FDG) and thus is a better biomarker in pancreatic cancer. Alovudine shows anti-orthopoxvirus and anti-leukemic activity^{[1][2][3][4][5][6]}. In Vitro:Alovudine (5-2000 nM, 6-10 days) depletes mitochondrial DNA, reduces mitochondrial encoded proteins, decreases basal oxygen consumption, decreases cell proliferation and viability, and promotes monocytic differentiationin in AML cells (OCI-AML2 and MV4-11)^[3].
Alovudine significantly augmentes DNA damage in BRCA1^-/- DT40 cells^[4].
Alovudine (0.5-2.5 μM, 6 days) prevents spontaneous cancer cell (MDA-MB-231) metastasis, without significant toxicity^[5].
In Vivo:Alovudine (50 mg/kg bid, p.o., 14 days) reduces the growth of leukemia in mouse models of human leukemia^[3].
Alovudine (50-250 μM, 9 days) prevents tumour growth and metastasis in pre-clinical animals implanted into MDA-MB-231 tumour cells^[5].
Alovudine (25 mg/kg (a loading dose of 25 mg/kg in 5 minutes), i.v.) reaches the extracellular fluid of the brain not by cerebrospinal fluid, but via the cerebral capillaries in rats^[6].