Alvespimycin

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的口服生物可利用的 Hsp90 抑制剂，结合 EC50 为 62 nM。

A potent, orally bioavailable Hsp90 inhibitor with binding EC50 of 62 nM; also show comparable binding affinity for Grp94 with EC50 of 65 nM; inhibits the migration and the extracellular matrix-invasiveness of HUVEC in vitro, also inhibits FGF-2 and VEGF-induced HUVEC proliferation and induces apoptosis.Blood Cancer Phase 1 Discontinued.

Alvespimycin (17-DMAG) is a potent inhibitor of Hsp90, binding to Hsp90 with an EC50 of 62 nM. Alvespimycin (17-DMAG) inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC50 of 8 ± 4 nM and 46 ± 24 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC50 of 4 ± 2 nM and 14 ± 7 nM in SKBR3 and SKOV3 cells, respectively. Compared with the vehicle control, Alvespimycin (17-DMAG) dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin (17-DMAG) also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition,Alvespimycin (17-DMAG) is much more potent after 24 and 48 hours of treatment than 17-AAG.

The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin (17-DMAG). Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals. HSP90 inhibitors have been shown to cause liver toxicity in an animal model of gastrointestinal cancer. Nevertheless, the reduction in tumor size using dipalmitoyl-radicicol is statistically significant at 100 mg/kg, while Alvespimycin (17-DMAG) at either 10 or 20 mg/kg elicits a significant reduction in tumor size.

17-DMAG | KOS-1022 | NSC-707545

Cytoskeleton/Cell Adhesion Molecules

HSP

HSP

Cancer

Blood cancer

467214-20-6

616.7455

C32H48N4O8

>98% (HPLC)

10 mM in DMSO

NC(O[C@@H](/C(C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC1=C2NCCN(C)C)[C@@H](OC)/C=C\C=C(C)\C(NC(C1=O)=CC2=O)=O)=O

Geldanamycin, 17-demethoxy-17-[[2-(dimethylamino)ethyl]amino]-

(-20℃)

With Ice Pack

≥ 2 years