6-Aminonicotinamide (Synonyms: 6-AN,NSC 21206,SR 4388) |
| Catalog No.GC10462 |
니코틴아미드의 강력한 항대사물질인 6-아미노코틴아미드는 경쟁적인 NADP+- 의존성 효소 글루코스-6-포스페이트 탈수소효소(G6PD) 억제제(Ki=0.46μM)입니다. 6-아미노코틴아미드는 해당과정을 방해하여 ATP를 고갈시키고 시스플라틴(Cisplatin)과 같은 DNA 가교 화학요법 약물과 시너지 효과를 일으켜 암세포를 죽입니다.
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Cas No.: 329-89-5
Sample solution is provided at 25 µL, 10mM.
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Ki: 0.46 μM
6-Aminonicotinamide is a 6-phosphogluconate dehydrogenase inhibitor.
6-Phosphogluconate dehydrogenase, an enzyme in the pentose phosphate pathway, can produce ribulose 5-phosphate from 6-phosphogluconate. 6-Phosphogluconate dehydrogenase is also an oxidative carboxylase catalyzing the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP.
In vitro: 6-Aminonicotinamide could be metabolized to 6-amino-NAD(P+), a competitive inhibitor of NAD(P+)-requiring processes, especially the pentose phosphate pathway enzyme, 6-phosphogluconate dehydrogenase. Moreove, 6-aminonicotinamide as a single agent could cause a significant inhibition of glycolytic flux but had no effect on the pentose phosphate pathway. 31P-NMR studies of perifused RIF-1 cells indicated that 4 h of exposure to 6-aminonicotinamide was enough to cause significant accumulation of 6-phosphogluconate, the substrate for this enzyme [1].
In vivo: The influence of 6-aminonicotinamide on the G-6-P-DH- and 6-PG-DH-levels of the pentose phosphate pathway in the kidney was investigated. Following i.p. administration of 6-aminonicotinamide at 6 mg/kg, the 6-PG-level rose from a value less than 10 nmoles/g to 1000 nmoles/g fresh weight within 24 h. In addition, at the end of the assay, after 7 days, a 6-PG-concentration of about 150 nmoles/g fresh weight was still seen. Moreove, the G-6-P level simultaneously rose with the 6-PG-level to about 150% of the control level and returned to normal on the 5th day [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Street, J. C.,Alfieri, A.A. and Koutcher, J.A. Quantitation of metabolic and radiobiological effects of 6-aminonicotinamide in RIF-1 tumor cells in vitro. Cancer Research 57, 3956-3962 (1997).
[2] Lange, K. and Proft, E.R. Inhibition of the 6-phosphogluconate dehydrogenase in the rat kidney by 6-aminonicotinamide. Naunyn-Schmiedeberg's Archives of Pharmacology 267, 177-180 (1970).
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