HSP90/mTOR-IN-1 是一种有效的Hsp90和mTOR抑制剂，IC50分别为 69 nM 和 29 nM。HSP90/mTOR-IN-1 通过过度激活PI3K/AKT/mTOR通路抑制 SW780 细胞增殖。HSP90/mTOR-IN-1 通过对 HSP90 和 mTOR 的选择性抑制来诱导细胞凋亡 (apoptosis) 和细胞自噬 (autophagy)。HSP90/mTOR-IN-1 在异种移植小鼠体内也表现出良好的抗肿瘤活性。HSP90/mTOR-IN-1 可用于膀胱癌的研究。
| 生物活性 | HSP90/mTOR-IN-1 is a potent and orally activeHsp90andmTORinhibitor withIC50values of 69 nM and 29 nM, respectively. HSP90/mTOR-IN-1 suppresses the proliferation of SW780 cells through the over-activation of thePI3K/AKT/mTORpathway. HSP90/mTOR-IN-1 inducesapoptosisandautophagyvia selectiveHsp90andmTORinhibition. HSP90/mTOR-IN-1 also has considerablein vivoanti-tumor activity. HSP90/mTOR-IN-1 can be used for researching bladdercancer[1]. |
| IC50& Target[1] | mTOR 29 nM (IC50) | HSP90 69 nM (IC50) |
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体外研究
(In Vitro) | HSP90/mTOR-IN-1 (compound 17o) has antiproliferative activity against J82, T24 and SW780 cells[1].
HSP90/mTOR-IN-1 (0.2 and 0.5 μM; 24 h) induces SW870 apoptosis in a dose-dependent manner, induces the formation of autophagosome[1].
HSP90/mTOR-IN-1 (0.2 and 0.5 μM; 24 h) decreases the expression of several Hsp90 client proteins in SW870[1].
Cell Proliferation Assay[1] | Cell Line: | J82, T24 and SW780[1] | | Concentration: | 0-1 μM | | Incubation Time: | 48 h | | Result: | Exhibited antiproliferative activity against J82, T24 and SW780 with IC50s of 0.36 ± 0.03 μM, 0.41 ± 0.06 μM, 0.16 ± 0.03 μM. |
Apoptosis Analysis[1] | Cell Line: | SW870 | | Concentration: | 0.2 and 0.5 μM | | Incubation Time: | 24 h | | Result: | Induced apoptosis in a dose-dependent manner (total apoptotic cell percentage was 12.4% and 16.5% at 0.2 and 0.5 μM, respectively). |
Cell Autophagy Assay[1] | Cell Line: | SW870 (transfected with GFP-LC3) | | Concentration: | 0.2 and 0.5 μM | | Incubation Time: | 24 h | | Result: | Induced the formation of autophagosome.
The green fluorescent spots were observed to increase in the number and gathered. |
Western Blot Analysis[1] | Cell Line: | SW870 | | Concentration: | 0.2 and 0.5 μM | | Incubation Time: | 24 h | | Result: | Significantly decreased the expression of several Hsp90 client proteins, CDK4, C-Raf and CDC2. |
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体内研究
(In Vivo) | HSP90/mTOR-IN-1 (30 mg/kg; PO; for 17 days) exhibits significantly superior tumor growth inhibition in J82 xenograft mice[1].
| Animal Model: | Balc/c nude mice (6-8 weeks; subcutaneously injected with 1×106cells per 100 μL of J82 cells into the mice's dorsal skin)[1] | | Dosage: | 30 mg/kg | | Administration: | PO; for 17 days | | Result: | Exhibited significantly superior tumor growth inhibition, and did not showed remarkable weight decline.
Inhibited bladder cancer cell proliferation, induced cell apoptosis, degraded Hsp70, as well as decreased phosphorylation levels of mTOR and increased expression of LC3-II. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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