17-AAG (Tanespimycin; 17-N-Allylamino-17-demethoxygeldanamycin) is a geldanamycin- derived anti-tumor agent currently used in cancer research. It is an inhibitor of heat shock protein 90. The compound epletes cellular STK38/NDR1 and reduces STK38 kinase activity.
17-AAG is soluble in DMSO but practically insoluble in water.
|Mechanism of Action||17-AAG targets and inactivates Hsp90 (heat shock protein 90), which is expressed in certain types of leukimia and lymphomas as well as solid tumors.|
|Eukaryotic Cell Culture Applications||17-AAG has been shown to induce cell-cycle arrest and apoptosis in cultured ALCL cells irrespective of ALK expression. In addition, 17-AAG has shown promising results in the treatment of uveal melanoma through inhibition of HSP-90 in tandem with c-Kit inhibition.|
|Cancer Applications||Canine osteosarcoma is highly resistant to chemotherapy. An investigation with 17-AAG in canine osteosarcoma cell lines was undertaken to understand the relationship between cell death, autophagy and mitophagy in regulating cancer cell viability and death. Authors tested 2 cell lines (D22, and D17 from primary and metastatic tumors respectively. Authors found that 17-AAG caused a simultaneous increase in apoptosis and autophagy, and mitophagy was observed in the D22 cell lines, but only slight apoptosis in the D17 cell line. This study revealed that a treatments based on pro-apoptotic chemotherapy with autophagy regulators could benefit from in-vitro screening, since there are differences in cell responses based on cell type (Massimini et al, 2017).|
Hawkins LM, Jayanthan AA, Narendran A (2005) Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on pediatric acute lymphoblastic leukemia (ALL) with respect to Bcr-Abl status and imatinib mesylate sensitivity. Pediatr Res. 57(3):430-437
Massimini M et al (2017) 17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines. Vet. Pathol. 54(3):405-412
Radujkovic A et al (2005) Synergistic activity of imatinib and 17-AAG in imatinib-resistant CML cells overexpressing BCR-ABL--Inhibition of P-glycoprotein function by 17-AAG. Leukemia. 19(7):1198-1206