Luminespib  (Synonyms: VER-52296; AUY922; NVP-AUY922)

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

Luminespib is a potent and selective HSP90 inhibitor, with IC₅₀s and K_is of 21 ± 16, 8.2 ± 0.7 nM against HSP90β and of 7.8 ± 1.8, 9.0 ± 5.0 nM for HSP90α. Luminespib shows weak activity against GRP94 and TRAP-1 wich IC₅₀s of 535 ± 51 nM (K_i, 108 nM) and 85 ± 8 nM (K_i, 53 nM), respectively. Luminespib exhibits inhibitory effect on proliferation of various human tumor cell lines (2.3-49.6 nM), induces cell cycle arrest and apoptosis and depletes client proteins in human cancer cells (80 nM)^[1]. Luminespib (100 nM) significantly reduces CD40L fibroblast-induced changes in immunophenotype and STAT3 signaling but with no effect on the viability of chronic lymphocytic leukemia (CLL) cells. Luminespib (500 nM) in combination with NSC 118218 more effectively induces apoptosis in cells in co-culture than either drug alone, and overcomes fibroblast-derived resistance to Hsp90 inhibitor^[2]. Luminespib shows great inhibition of pancreatic cancer cells with IC₅₀ of at 10 nM. Luminespib (10 nM) reduces the expression and the epidermal growth factor (EGF)-mediated activation of EGFR and substantially disrupts EGF signaling in terms of diminishing downstream phosphorylation of ERK^{Thr202/Tyr204}. Luminespib (10 nM) significantly blocks pancreatic cancer cell migration and invasion both in the absence and presence of EGF^[3].

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

Luminespib (50, 75 mg/kg, i.p.) significantly inhibits tumor growth rate, reducing the mean weights of tumors on day 11 in human tumor xenografts^[2]. Luminespib (50 mg/kg/week, 3×25 mg/kg/week) significantly reduces tumor growth rates and lowers tumor weights in the L3.6pl pancreatic cancer cell-bearing mice model^[3].

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

465.54

C₂₆H₃₁N₃O₅

747412-49-3

Solid

Light yellow to gray

O=C(C1=NOC(C2=CC(C(C)C)=C(O)C=C2O)=C1C3=CC=C(CN4CCOCC4)C=C3)NCC

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [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]