55.抗肿瘤药物格尔德霉素的合作研发

日期：2020-11-11 阅读量：664

格尔德霉素(Geldnamycin)是一种新型强效苯醌安莎类抗生素,其具有广泛的抗菌谱,并具有抗病毒、抗原虫、抗肿瘤等生物活性。通过蛋白质分子伴侣---热休克蛋白起作用，影响底物的正常折叠而降解，从而达到目的。

Geldanamycin and derivates thereof are a family of a benzoquinone ansamycins, antibiotics originally isolated on the basis of their weak antibiotic activity that were subsequently shown to display potent antitumor activity.

Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-src, bcr-abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, Geldanamycin has several major disadvantages as a remedy candidate that have led to the development of Geldanamycin analogues, in particular analogues containing a substitution on the 17 position:17-AAG, 17-DMAG and some others.

Geldanamycin is a natural product produced by Streptomyces hygroscopicus in submerged fermentation.

Geldanamycin binds with high affinity into the ATP binding pocket of Hsp 90. Hsp 90 is a ubiquitous molecular chaperone critical for the folding, assembly and activity of multiple mutated and overexpressed signaling proteins that promote the growth and/or survival of tumor cells. Hsp 90 target proteins include mutated p53, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1a (HIF-1a). Binding of Geldanamycin to Hsp 90 causes the destabilization and degradation of its client proteins.

Formula: C₂₉H₄₀N₂O₉ 

Molecular weight: 560.64

CAS Number: 30562-34-6

Appearance: yellow powder