HSP990 (NVP-HSP990)

Catalog No.S7097

For research use only.

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.

HSP990 (NVP-HSP990) Chemical Structure

CAS No. 934343-74-5

Selleck's HSP990 (NVP-HSP990) has been cited by 5 Publications

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Biological Activity

Description 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.
Features NVP-HSP990 is an orally available HSP90 inhibitor and is structurally distinct from other clinical HSP90 inhibitors.
Targets
HSP90α [1]
(Cell-free assay)
HSP90β [1]
(Cell-free assay)
0.6 nM 0.8 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A2058 cells MYDDfZRwfG:6aXPpeJkh[XO|YYm= NYfGXpByS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTJyNUigZ4VtdHNiaX6gdJJme2WwY3Wgc4YhUFOIMTDrco9kcyCmb4fuJJRz\WG2bXXueEwhUUN3ME2wMlAxPTJizszN M{[zfVI3OTZ2MUi4
human A375 cells NYfqTZUxS3m2b4TvfIlkcXS7IHHzd4F6 M4D1[mN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE{PzViY3XscJMhcW5icILld4Vv[2Vib3[gTHNHOSCtbn;jb{Bld3ewIITy[YF1dWWwdDygTWM2OD1yLkCwOkDPxE1? M4PRS|I3OTZ2MUi4
human GTL16 cells NGrsWZZEgXSxdH;4bYNqfHliYYPzZZk> MXe3NkBp NWnObHY2S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hT1SOMU[gZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRz\S2JbH:gZZN{[XluIFnDOVA:OC5yMUSg{txO M2PMR|I2OzZ6OUi0
Assay
Methods Test Index PMID
Western blot HSP90 / HSP70 ; EGFR / ErbB2 / ErbB3 / IGF-1R ; p-Akt / Akt / p-ERK / ERK / pp70S6K / p70S6K / p4EBP1 / 4EBP1 24100469
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]

Protocol (from reference)

Kinase Assay:

[1]

  • HSP90 binding, ATPase, and selectivity profiling assays:

    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 Research:

[2]

  • Cell lines: GICs
  • Concentrations: ~1 μM
  • Incubation Time: 7 days
  • Method:

    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.

Animal Research:

[1]

  • Animal Models: GTL-16, NCI-H1975, BT474, and MV4;11 tumor xenografted nude and SCID mice models
  • Dosages: 15 mg/kg
  • Administration: Oral

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 379.39
Formula

C20H18FN5O2

CAS No. 934343-74-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C2C(=NC(=N1)N)CC(NC2=O)C3=C(C=C(C=C3)F)C4=NC(=CC=C4)OC

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00879905 Completed Drug: HSP990 Advanced Solid Malignancies Novartis Pharmaceuticals|Novartis May 2009 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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