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HSP990(NVP-HSP990)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
HSP990(NVP-HSP990)图片
CAS NO:934343-74-5
规格:≥98%
包装与价格:
包装价格(元)
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)379.39
FormulaC20H18FN5O2
CAS No.934343-74-5
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 75 mg/mL (197.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)Chemical Name: (R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one
InChi Key: WSMQUUGTQYPVPD-OAHLLOKOSA-N
InChi Code: InChI=1S/C20H18FN5O2/c1-10-18-16(26-20(22)23-10)9-15(25-19(18)27)12-7-6-11(21)8-13(12)14-4-3-5-17(24-14)28-2/h3-8,15H,9H2,1-2H3,(H,25,27)(H2,22,23,26)/t15-/m1/s1
SMILES Code: O=C1N[C@@H](C2=CC=C(F)C=C2C3=NC(OC)=CC=C3)CC4=NC(N)=NC(C)=C41
SynonymsNVP HSP 990; NVP-HSP990; HSP990; HSP-990; HSP 990; NVP HSP-990
实验参考方法
In Vitro

In vitro activity: 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. 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.


Kinase Assay: 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.


Cell Assay: 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.

In VivoNVP-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.
Animal modelGTL-16, NCI-H1975, BT474, and MV4;11 tumor xenografted nude and SCID mice models
Formulation & DosageDissolved in 100% polyethylene glycol (PEG400); 15 mg/kg; oral gavage
References

Mol Cancer Ther. 2012 Mar;11(3):730-9; Cancer Res. 2013 May 15;73(10):3062-74.