HSP990 (NVP-HSP990)

製品コードS7097 バッチS709701

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H18FN5O2
分子量 379.39 CAS No. 934343-74-5
Solubility (25°C)* 体外 DMSO 75 mg/mL (197.68 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 HSP990 (NVP-HSP990) is a novel, potent and selective HSP90 inhibitor for HSP90α/β with IC50 of 0.6 nM/0.8 nM. NVP-HSP990 induces cell cycle arrest and apoptosis.
in vitro HSP990 (NVP-HSP990) is based on a 2-amino-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one scaffold, which is structurally distinct from other known HSP90 inhibitors. It binds to the N-terminal ATP-binding domain of HSP90 and exhibits single digit nanomolar IC50 values on three of the HSP90 isoforms (HSP90α, HSP90β, and GRP94) and 320 nM IC50 value on the fourth (TRAP-1), with selectivity against unrelated enzymes, receptors, and kinases. This compound dissociates the HSP90-p23 complex, depleted client protein c-Met, and induced Hsp70 in c-Met amplified GTL-16 gastric tumor cells. It potently inhibites the growth of human cell lines and primary patient samples from a variety of tumor types. [1] NVP-HSP990 displays dose- and time-dependent effects on HSP90 client proteins. It inhibits Glioma tumor-initiating cells (GIC) proliferation in all GIC lines, with IC50 values ranging approximately between 10 and 500 nM. Olig2 is a functional marker associated with cell proliferation and response to this compound, as it attenuated cell proliferation in Olig2-high GIC lines. In addition, it disrupted cell-cycle control mechanism by decreasing CDK2 and CDK4 and elevating apoptosis-related molecules. [2]
in vivo HSP990 (NVP-HSP990) exhibits drug-like pharmaceutical and pharmacologic properties with high oral bioavailability. In the GTL-16 xenograft model, a single oral administration of 15 mg/kg of this compound induced sustained downregulation of c-Met and upregulation of Hsp70. In repeat dosing studies, it resulted in tumor growth inhibition of GTL-16 and other human tumor xenograft models driven by well-defined oncogenic HSP90 client proteins. [1]
特徴 NVP-HSP990 is an orally available HSP90 inhibitor and is structurally distinct from other clinical HSP90 inhibitors.

プロトコル(参考用のみ)

キナーゼアッセイ HSP90 binding, ATPase, and selectivity profiling assays
The potency of HSP990 (NVP-HSP990) for HSP90α, HSP90β, and Grp94 is determined by AlphaScreen competition binding assays, and its activity against TRAP-1 is assessed by an ATPase assay.
細胞アッセイ 細胞株 GICs
濃度 ~1 μM
反応時間 7 days
実験の流れ

Dissociated GICs are plated at 10 cells/μL in 6-well plates and incubated with various concentrations of NVP-HSP990 for 7 days. Formed tumorspheres are dissociated into single cells and counted with hemocytometer using 0.2% Trypan blue exclusion.
動物実験 動物モデル GTL-16, NCI-H1975, BT474, and MV4;11 tumor xenografted nude and SCID mice models
投薬量 15 mg/kg
投与方法 Oral

参考

  • https://pubmed.ncbi.nlm.nih.gov/22246440/
  • https://pubmed.ncbi.nlm.nih.gov/23492364/

カスタマーフィードバック

Data from [Data independently produced by , , Cancer Sci, 2018, 109(2):373-383]

Data from [Data independently produced by , , Am J Transl Res,2015, 7(12):2589-602.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression [ Autophagy, 2025, 1-23.] PubMed: 40114316
Heat shock protein 90 chaperone activity is required for hepatitis A virus replication [ J Virol, 2025, e0050225] PubMed: 40470959
Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging [ J Labelled Comp Radiopharm, 2025, 68(4):e4144] PubMed: 40219580
A novel PET probe to selectively image heat shock protein 90α/β isoforms in the brain [ EJNMMI Radiopharm Chem, 2024, 9(1):19] PubMed: 38436869
Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses [ Virus Res, 2023, 329:199103] PubMed: 36963723
HSP90 inhibitor NVP-HSP990 alleviates rotavirus infection [ bioRxiv, 2023, 10.1101/2023.06.15.545197] PubMed: none
Deciphering the immunopeptidome in vivo reveals new tumour antigens [ Nature, 2022, 607(7917):149-155] PubMed: 35705813
The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma [ EMBO Mol Med, 2022, 14(12):e15677] PubMed: 36305167
A STUB1 ubiquitin ligase/CHIC2 protein complex negatively regulates the IL-3, IL-5, and GM-CSF cytokine receptor common β chain (CSF2RB) protein stability [ J Biol Chem, 2022, 298(10):102484] PubMed: 36108743
Drosophila melanogaster as a model for unraveling unique molecular features of epilepsy elicited by human GABA transporter 1 variants [ Front Neurosci, 2022, 16:1074427] PubMed: 36741049

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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