NVP-HSP990

HSP90 (heat shock protein 90) is a cellular ubiquitous molecular chaperone responsible for promoting the conformational mutation and stabilization of several client oncoproteins, including Met, B-Raf, p53, Akt, and Kit, function of which is required by tumor cells to maintain appropriate client protein expression necessary for proliferation and survival. HSP990 is a potent HSP90 inhibitor with IC50 value of 0.6nM and 0.8nM for Hsp90α and Hsp90β (AlphaScreen competition binding assays), respectively, as well as shows inhibition against GRP94, an HSP90-like protein with IC50 value of 8.5nM. Treatment with HSP990 at concentration of 250nM over 30min could dissociate the complex of HSP90-p23, thus leading to the downregulation of the client protein c-Met and induction of HSP70, the biomarker for HSP90 inhibition, in c-Met amplified GTL-16 gastric tumor cells. In a study of a panel of cell lines and primary patient samples from a variety of tumor types, HSP990 showed anti-proliferation against most of the cells evaluated irrespective of cancer types or genetics, with GI50 values ranging in 4–40nM. In vivo study showed that HSP990 exhibited drug-like pharmaceutical and pharmacologic properties with high oral bioavailability, shown as sustained downregulation of c-Met and upregulation of Hsp70 induced by a single oral administration of 15 mg/kg HSP990. Oral administration of led to significant tumor growth inhibition in the BT-474 breast cancer model at dose of 5mg/kg or 10mg/kg HSP990 per week for 3 weeks, and in the MV4;11 AML model at dose of 5mg/kg twice a week or 10mg/kg once a week for 18 days¹.

溶解方案(细胞实验)

DMSO 中的溶解度 : ≥ 33 mg/mL (86.98 mM; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|* "≥" means soluble, but saturation unknown.

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.08 mg/mL (5.48 mM); 澄清溶液 此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.08 mg/mL (5.48 mM); 澄清溶液 此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"