HSP990 (NVP-HSP990)

製品コードS7097 バッチS709703

化学情報

	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	76 mg/mL (200.32 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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	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. NVP-HSP990 binds to the N-terminal ATP-binding domain of HSP90. NVP-HSP990 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. NVP-HSP990 dissociates the HSP90-p23 complex, depleted client protein c-Met, and induced Hsp70 in c-Met amplified GTL-16 gastric tumor cells. NVP-HSP990 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. NVP-HSP990 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 NVP-HSP990, as NVP-HSP990 attenuated cell proliferation in Olig2-high GIC lines. In addition, NVP-HSP990 disrupted cell-cycle control mechanism by decreasing CDK2 and CDK4 and elevating apoptosis-related molecules. ^[2]
in vivo	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 NVP-HSP990 induced sustained downregulation of c-Met and upregulation of Hsp70. In repeat dosing studies, NVP-HSP990 treatment 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
キナーゼアッセイ	The potency of HSP90 inhibitors for HSP90α, HSP90β, and Grp94 is determined by AlphaScreen competition binding assays, and 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

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.]

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Deciphering the immunopeptidome in vivo reveals new tumour antigens [ Nature, 2022, 607(7917):149-155]	PubMed: 35705813
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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
Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity [ Theranostics, 2020, 10(18):8415-8429]	PubMed: 32724478
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