Structure of Tanespimycin
CAS No.: 75747-14-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Tanespimycin (17-AAG) is a potent HSP90 inhibitor with an IC50 of 5 nM, showing a 100-fold higher binding affinity for tumor-derived HSP90 than normal cell-derived HSP90. Tanespimycin depletes cellular STK38/NDR1, reduces STK38 kinase activity, and downregulates the stk38 gene expression.
Synonyms: 17-AAG; NSC 330507; 17-AAG, 17 AAG, 17AAG, BAY 57-9352, BAY 579352, BAY579352, KOS-953, KOS-953, KOS-953, Tanespimycin
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Wnuk, Maciej ; Del Sol-Fernández, Susel ; Błoniarz, Dominika ; Słaby, Julia ; Szmatoła, Tomasz ; Żebrowski, Michał , et al.
Abstract: The accumulation of senescent cells, a hallmark of aging and age-related diseases, is also considered as a side effect of anticancer therapies, promoting drug resistance and leading to treatment failure. The use of senolytics, selective inducers of cell death in senescent cells, is a promising pharmacological antiaging and anticancer approach. However, more studies are needed to overcome the limitations of first-generation senolytics by the design of targeted senolytics and nanosenolytics and the validation of their usefulness in biological systems. In the present study, we have designed a nanoplatform composed of iron oxide nanoparticles functionalized with an antibody against a cell surface marker of senescent cells (CD26), and loaded with the senolytic drug HSP90 inhibitor 17-DMAG (MNP@CD26@17D). We have documented its action against oxidative stress-induced senescent human fibroblasts, WI-38 and BJ cells, and anticancer drug-induced senescent cutaneous squamous cell carcinoma A431 cells, demonstrating for the first time that CD26 is a valid marker of senescence in cancer cells. A dual response to MNP@CD26@17D stimulation in senescent cells was revealed, namely, apoptosis-based early response (2 h treatment) and ferroptosis-based late response (24 h treatment). MNP@ CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance.
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Keywords: iron oxide nanoparticles ; CD26 ; HSP90 inhibitor ; drug-induced senescence ; skin cells ; senolysis
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CAS No. : | 75747-14-7 |
Formula : | C31H43N3O8 |
M.W : | 585.69 |
SMILES Code : | C=CCNC1=C2C(C(NC(/C(C)=C/C=C\[C@@H]([C@H](/C(C)=C/[C@@H]([C@H]([C@H](C[C@@H](C2)C)OC)O)C)OC(N)=O)OC)=O)=CC1=O)=O |
Synonyms : |
17-AAG; NSC 330507; 17-AAG, 17 AAG, 17AAG, BAY 57-9352, BAY 579352, BAY579352, KOS-953, KOS-953, KOS-953, Tanespimycin
|
MDL No. : | MFCD04973892 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
DU145 human prostate cancer cells | 230 nM | 72 h | To evaluate the growth inhibitory effect of SMA-tanespimycin micelles on DU145 human prostate cancer cells, results showed an IC50 of 230 nM. | PMC3195848 |
HeLa cells | 500 nM | 18 h | To study the effect of 17-AAG on Hsp90 conformation, results showed that 17-AAG induced conformational changes in Hsp90, including the closing of the ATP-binding pocket and increased interaction between the NTD and MD. | PMC5012217 |
HCC827 | 0.25 µM | 72 h | To observe the effect of HSP90 inhibitor 17AAG on HCC827 cells, results showed that p53 remained constant in 3D conditions but was activated in 2D conditions. | PMC6068345 |
A549 | 0.25 µM | 72 h | To observe the effect of HSP90 inhibitor 17AAG on A549 cells, results showed that HSP60 was significantly upregulated in 3D conditions. | PMC6068345 |
H441 | 0.25 µM | 72 h | To observe the effect of HSP90 inhibitor 17AAG on H441 cells, results showed that p53 was activated in 3D conditions but remained unchanged in 2D conditions. | PMC6068345 |
Leishmania mexicana promastigotes | 2 μM, 10 μM, 25 μM | 2 h | To investigate the effects of Hsp90 inhibition on nascent protein synthesis in Leishmania mexicana. The results showed that 25 μM tanespimycin significantly decreased nascent protein synthesis, indicating that Hsp90 inhibition significantly affects protein translation. | PMC8125071 |
Leishmania mexicana promastigotes | 50 μM | 1 h, 4 h | To assess the temporal effect of tanespimycin treatment on global protein synthesis in Leishmania mexicana. The results showed that 4 h of Hsp90 inhibition significantly decreased global nascent protein synthesis, indicating that severe Hsp90 inhibition affects protein translation. | PMC8125071 |
Z138 cells | 0.5 and 1.0 µM | 24 h | To evaluate the effect of Tanespimycin on Z138 cells, results showed that Tanespimycin significantly inhibited the expression of MYC and CDK9 and induced cell apoptosis. | PMC10848414 |
HT29 colon adenocarcinoma cells | 62.5 nM | 8 h | To investigate changes in protein complexes following HSP90 inhibition, results showed limited changes in protein complex distribution after HSP90 inhibition. | PMC9898794 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
nude mice | subcutaneous DU145 human prostate cancer tumor xenografts | tail vein injection | 10 mg/kg | single dose, lasting 23 days | To evaluate the anti-cancer efficacy of SMA-tanespimycin micelles in nude mice bearing subcutaneous DU145 human prostate cancer tumor xenografts, results showed significant tumor growth inhibition. | PMC3195848 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT00779428 | Advanced Malignancies | PHASE2 | COMPLETED | 2025-07-13 | Dana-Farber Cancer Institute, ... More >>Boston, Massachusetts, 02115, United States Less << |
NCT00773344 | Solid Tumors|Breast Cancer | PHASE1|PHASE2 | COMPLETED | 2025-08-09 | Premiere Oncology Of Arizona, ... More >>Scottsdale, Arizona, 85260, United States|Arizona Cancer Center, Tucson, Arizona, 85724, United States|Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
1.71mL 0.34mL 0.17mL |
8.54mL 1.71mL 0.85mL |
17.07mL 3.41mL 1.71mL |
Tags: Tanespimycin | 17-AAG | NSC 330507 | CP 127374 | NSC330507 | NSC 330507 | NSC-330507 | CP127374 | CP 127374 | CP-127374 | HSP | Autophagy | Mitophagy | Apoptosis | Heat shock proteins | Mitochondrial Autophagy | AR | HER2 | STK38 kinase | HSP90 inhibitor | 17-AAG | proteasomal degradation | 75747-14-7
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