生物活性

17-DMAG can bind to the ATP-binding motif of Hsp90 and inhibit the protein chaperoning activity of Hsp90. It will cause misfolding and subsequent degradation of Hsp90’s client proteins, such as EGFR, AKT, mutant p53, and IKK. Since there are more specific conformation Hsp90 required for 17-DMAG binding in tumor cells and many client proteins of Hsp90 contribute to tumor cell growth, 17-DMAG is usually more toxic to tumor cells than to normal cells.

体外研究

体内研究

1% DMSO+30% polyethylene glycol+1% Tween 80

激酶实验

细胞实验

~1 μM

动物实验

10 mg/kg 腹腔注射，每周5次

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Ge J, et al. J Med Chem, 2006, 49(15), 4606-4615.
[2] Egorin et al (2002) Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and fischer 344 rats. Cancer Chemother.Pharmacol. 49 7.
[3] Smith et al (2005) Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Cancer Chemother.Pharmacol. 56 126.
[4] Dote et al (2006) Inhibition of Hsp90 compromises the DNA damage response to radiation. Cancer Res. 66 9211.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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