| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 25mg | 电议 |
| 100mg | 电议 |
Cell lines | Human bone marrow cells |
Preparation Method | In the protection studies, cells are exposed to 10 nM of tubercidin in the presence or absence of various doses of NBMPR-P. Cells are continuously exposed to drugs for 14 days in a humidified atmosphere of 5% C02-95% air at 37°c. Colonies of CFU-GM (250 cells) and BFU-E (30 hemoglobinized cells) are counted with an inverted microscope. |
Reaction Conditions | 10 nM of tubercidin ；14 days in a humidified atmosphere of 5% C02-95% air at 37°c |
Applications | Tubercidin alone had a direct dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells, and consistent inhibition (50%) of granulocyte-macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E) occurred at 2 to 3 nM tubercidin. At higher doses, BFU-E were more sensitive to tubercidin toxicity than CFU-GM. Complete inhibition (99%) of BFU-E colonies occurred at 10 nM tubercidin, while complete inhibition of CFU-GM occurred at 100 nM. NBMPR-P at 10 to 100 nM protected CFU-GM and BFU-E from tubercidin toxicity in a dose-dependent matter. |
Animal models | 35 female (20- to 25-g) CD1 mice |
Preparation Method | Three groups of mice were used, each consisting of 35 female (20- to 25-g) CD1 mice, The first group received four successive daily intraperitoneal injections of tubercidin (5 mg/kg per dose) plus NBMPR-P (25 mg/kg per dose) ; the regimen was repeated after a 10-day rest period . The second group received four daily injections of tubercidin (5 mg/kg per dose) alone, but the regimen could not be repeated owing to the death of mice within 3 to 5 days of the initiation of treatment. The third group (controls) received saline solution (0.9% NaCI). Drugs were prepared and administered as previously described. All mice that survived were sacrificed 4 days after the last injection. Whole blood was obtained by cardiac puncture and collected in a Unopette microcollection system. |
Dosage form | 5 mg/kg per dose |
Applications | Tubercidin (7-deazaadenosine) plus nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) used in combination therapy of schistosomiasis was examined in vivo in mice and in vitro with human bone marrow progenitor cells. Four successive daily intraperitoneal injections of tubercidin at 5 mg/kg per day produced 100% mortality in mice within 3 to 5 days following the first injection, with massive peritonitis and intestinal obstruction secondary to abdominal adhesions. Coadministration of NBMPR-P (25 mg/kg per day) protected the mice from the lethality of tubercidin and allowed the repetition of the regimen for a second time with 100% survival until the mice were sacrificed 22 days following the first injection. Blood chemistry, hematological studies, and histological examinations showed no evidence for injury to the liver, kidney, spleen, pancreas, mesentery, or peritoneal mesothelium. |
| 产品描述 | Tubercidin is a pyrrolopyrimidine nucleoside analog with significant activity against schistosomal infections. It has also been tested as a cancer chemotherapeutic agent, but its utility has been limited by nephrotoxicity[8]. As one of the most potent inhibitors of human liver SAH-hydrolase, Tubercidin enters cells via nucleoside transporters[7]. Upon intracellular metabolism of tubercidin to its mono, di, and tri-phosphate esters, it can substitute for adenosine nucleotides, and thereby interfere in the synthesis of DNA, RNA, and protein. As a toxic adenosine analog with antiviral, antitrypanosomal, and antifungal functions. Inhibits multiple metabolic processes which includes: RNA processing, nucleic acid synthesis, protein synthesis, and methylation of tRNA through intracellular incorporation into nucleic acids. Acts as a plant antifungal, inhibits mammalian SAHH (SAH hydrolase), and blocks purine biosynthesis in Candida famata[1].Tubercidin has been studied for antiviral and anticancer properties, is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties[4,5]. In vitro, tubercidin alone had a direct dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells, and consistent inhibition (50%) of granulocyte-macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E) occurred at 2 to 3 nM tubercidin. At higher doses, BFU-E were more sensitive to tubercidin toxicity than CFU-GM. Complete inhibition (99%) of BFU-E colonies occurred at 10 nM tubercidin, while complete inhibition of CFU-GM occurred at 100 nM. NBMPR-P at 10 to 100 nM protected CFU-GM and BFU-E from tubercidin toxicity in a dose-dependent matter[3].Continuous exposure for 14 days to tubercidin alone is highly toxic to both human CFU-GM and BFU-E. The IC50s of tubercidin are 3.4±1.7 and 3.7±0.2 nM for CFU-GM and BFU-E, respectively. Tubercidin also has a direct dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells in vitro[6]. The inhibitor tubercidin proved to be highly antiviral against SARS-CoV-2, Tubercidin is a broad-spectrum MTase inhibitor active against both NSP16 and MTr1.tubercidin potently inhibited both NSP16 and MTr1 in vitro, further emphasizing that a concomitant inhibition of NSP16 and MTr1 is pivotal for effective antiviral treatment.[2,3] Host toxicity of the dose regimen of tubercidin plus nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) used in combination therapy of schistosomiasis. Coadministration of NBMPR-P (25 mg/kg per day) protected the mice from the lethality of tubercidin and allowed the repetition of the regimen for a second time with 100% survival until the mice were sacrificed 22 days following the first injection. Blood chemistry, hematological studies, and histological examinations showed no evidence for injury to the liver, kidney, spleen, pancreas, mesentery, or peritoneal mesothelium. References: |
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