KU-177 是Hsp90ATP 酶同系物 1 (Aha1) 的有效抑制剂，可消融Aha1驱动的Hsp90依赖性 tau 聚集增强。KU-177 还干扰Aha1/Hsp90相互作用 (IC50=4.08 μM)，但不影响Hsp90的再折叠荧光素酶的能力。KU-177 抑制癌细胞生长并诱导凋亡 (apoptosis)，可用于 Tau 病的研究。
| 生物活性 | KU-177 is a potent inhibitor ofHsp90ATPase homologue 1 (Aha1), ablatesAha1-driven enhancement of Hsp90-dependent tau aggregation. KU-177 also disruptsAha1/Hsp90interactions (IC50=4.08 μM) without inhibition of Hsp90’s ATPase activity. KU-177 can be used for tauopathies research[1][2]. |
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体外研究
(In Vitro) | KU-177 (50 μM; 48 h) hampers the proliferation of flow MRD-positive cells in both primary multiple myeloma (MM) and recurrent MM patient samples[1].
KU-177 (30 μM; 48 h) inhibits proteasome activity in AHSA1 WT/OE cells, PSMD2 WT/OE cells and ANBL6 WT/DR cells[1].
KU-177 abrogates the cellular proliferation and PI resistance induced by elevated AHSA1, and decreases the expression of CDK6 and PSMD2[1].
KU-177 (25 μM; 30 min; 37 ℃) inhibits recombinant P301L tau aggregation without inhibiting Hsp90 to refold luciferase[2].
KU-177 (10 μM; 24 h) exhibits the ability to disrupt interactions between Aha1 and Hsp90 in SH-SY5Y neuroblastoma cells and SK-BR-3 breast cancer cells, without significantly inhibition on Hsp90 client protein (Her2)[2].
Cell Proliferation Assay[1] | Cell Line: | ARP1 and H929 WT and AHSA1-OE cells | | Concentration: | 1 nM-100 μM | | Incubation Time: | 24, 48, 72 hours | | Result: | Decreased multiple myeloma (MM) cell proliferation and PI resistance induced by AHSA1/HSP90 in vitro. |
Cell Proliferation Assay[2] | Cell Line: | SH-SY5Y neuroblastoma cells and Her2 overexpressing SK-BR-3 breast cancer cells | | Concentration: | 10 μM | | Incubation Time: | 24 hours | | Result: | Didn’t induce the degradation of Hsp90 client proteins Her2 (in SK-BR-3 cells), Cdk6, or pAktS473 (in SHSY5Y cells), nor induced the expression of Hsp70, a marker of the heat shock response. |
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体内研究
(In Vivo) | KU-177 (1 mg/kg; i.p.; twice a week; 4 weeks), inhibits tumor growth and extends the survival of 5TMM3VT MM mice without significant toxicity. KU-177 shows stronger efficacy in vivo, combined withBortezomib(HY-10227) (1 mg/kg; i.p.)[1].
| Animal Model: | 5TMM3VT mouse model (6-8 weeks old, C57BL/KaLwrij mice)[1] | | Dosage: | 1 mg/kg | | Administration: | Intraperitoneal injection; twice a week; sacrificed mice with hindlimb weakness immediately, about 4-5 weeks | | Result: | Inhibited the xenograft tumor growth of both ANBL6 WT/BTZ-DR cells.
Didn’t induce histopathological abnormities or lesions in main organs including heart, liver, spleen, lung and kidney. |
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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. |
