Tubercidin

IC50: 3.4 and 3.7 nM for granulocyte-macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E), respectively

Tubercidin is an adenosine analog antibiotic agent.

Nucleoside antibiotics are a family of natural products with various biological functions. Their biosynthesis is a complex process via multistep enzymatic reactions.

In vitro: Previous study showed that tubercidin alone had a dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells. BFU-E were more sensitive at higher doses of tubercidin than CFU-GM. The 99% complete inhibition of BFU-E colonies was observed at 10 nM tubercidin, whereas complete inhibition of CFU-GM occurred at 100 nM [1].

In vivo: Animal toxicity study showed that four successive daily injections of tubercidin at 5 mg/kg per day could produce 100% mouse mortality within 3 to 5 days, with massive peritonitis and intestinal obstruction. In addition, coadministration of NBMPR-P at 25 mg/kg per day could protect the mice from the tubercidin lethality and allow the repetition of the regimen for a second time with 100% survival [1].

Clinical trial: Previous clinical study has been conduct to evaluate tubercidin administered after absorption into human erythrocytes, and the results showed that toxicity to the drug was uncommon and usually not severe. Moreover, the biological effect was obvious between 4 and 12 weeks after the onset of therapy [2].

References:
[1] el Kouni MH,Diop D,O'Shea P,Carlisle R,Sommadossi JP.  Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis. Antimicrob Agents Chemother.1989 Jun;33(6):824-7.
[2] Grage TB,Rochlin DB,Weiss AJ,Wilson WL.  Clinical studies with tubercidin administered after absorption into human erythrocytes. Cancer Res.1970 Jan;30(1):79-81.