Luminespib (VER-52296) is a potent HSP90 inhibitor with IC₅₀s of 7.8 and 21 nM for HSP90α and HSP90β, respectively^[1].

Luminespib 是一種強(qiáng)效且選擇性的 HSP90 抑制劑，對(duì) HSP90β 的 IC₅₀s 值和 K_is 值分別為 21 ± 16、8.2 ± 0.7 nM，對(duì) HSP90α 的 IC₅₀s 值和 K_is 值分別為 7.8 ± 1.8、9.0 ± 5.0 nM。Luminespib 對(duì) GRP94 和 TRAP-1 表現(xiàn)出較弱的活性，IC₅₀s 值分別為 535 ± 51 nM（K_i，108 nM）和 85 ± 8 nM（K_i，53 nM）。 Luminespib 對(duì)各種人類腫瘤細(xì)胞系的增殖有抑制作用 (2.3-49.6 nM)，誘導(dǎo)細(xì)胞周期停滯和凋亡，并消耗人類癌細(xì)胞中的客戶蛋白 (80 nM)^[1]。Luminespib (100 nM) 顯著降低 CD40L 成纖維細(xì)胞誘導(dǎo)的免疫表型和 STAT3 信號(hào)傳導(dǎo)變化，但對(duì)慢性淋巴細(xì)胞白血病 (CLL) 細(xì)胞的活力沒(méi)有影響。Luminespib (500 nM) 與 NSC 118218 聯(lián)合使用比單獨(dú)使用任何一種藥物更有效地誘導(dǎo)共培養(yǎng)細(xì)胞凋亡，并克服成纖維細(xì)胞對(duì) Hsp90 抑制劑的耐藥性^[2]。Luminespib 對(duì)胰腺癌細(xì)胞表現(xiàn)出很強(qiáng)的抑制作用，IC₅₀ 值為 10 nM。 Luminespib (10 nM) 可降低 EGFR 的表達(dá)和表皮生長(zhǎng)因子 (EGF) 介導(dǎo)的激活，并通過(guò)降低 ERK^{Thr202/Tyr204} 的下游磷酸化來(lái)顯著破壞 EGF 信號(hào)傳導(dǎo)。Luminespib (10 nM) 可在沒(méi)有和存在 EGF 的情況下顯著阻止胰腺癌細(xì)胞的遷移和侵襲^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Luminespib（50、75 mg/kg，腹腔注射）顯著抑制腫瘤生長(zhǎng)速度，降低人類腫瘤異種移植模型中第 11 天腫瘤的平均重量^[2]。
Luminespib（50 mg/kg/周，3×25 mg/kg/周）顯著降低 L3.6pl 胰腺癌細(xì)胞小鼠模型中的腫瘤生長(zhǎng)速度并降低腫瘤重量^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

465.54

C₂₆H₃₁N₃O₅

747412-49-3

固體

Light yellow to gray

Room temperature in continental US; may vary elsewhere.

• [1]. Eccles, Suzanne A., et al. NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis. Cancer Research (2008), 68(8), 2850-2860.  [Content Brief]

  [2]. Best OG, et al. Heat shock protein-90 inhibitor, NVP-AUY922, is effective in combination with NSC 118218 against chronic lymphocytic leukemia cells cultured on CD40L-stromal layer and inhibits their activated/proliferative phenotype. Leuk Lymphoma. 2012 Jul 9.  [Content Brief]

  [3]. Moser C, et al. Stoeltzing O.Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer. Anticancer Res. 2012 Jul;32(7):2551-61.  [Content Brief]