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HSP990 (NVP-HSP990) HSP inhibitor

Name: HSP990 (NVP-HSP990)
Brand: Selleck Chemicals
SKU: S7097
Availability: InStock
Rating: 5 (15 reviews)

Cat.No.S7097

HSP990 (NVP-HSP990) is a novel, potent and selective HSP90 inhibitor for HSP90α/β with IC50 of 0.6 nM/0.8 nM, and it induces cell cycle arrest and apoptosis.

Chemical Structure

Molecular Weight: 379.39

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability

Quality Control

Batch: Purity: 99.98%

99.98

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
human A2058 cells	Cytotoxicity assay		Cytotoxicity against human A2058 cells in presence of HSF1 knock down treatment, IC50=0.0052 μM
human A375 cells	Cytotoxicity assay		Cytotoxicity against human A375 cells in presence of HSF1 knock down treatment, IC50=0.006 μM
human GTL16 cells	Cytotoxicity assay	72 h	Cytotoxicity against human GTL16 cells after 72 hrs by CellTitre-Glo assay, IC50=0.014 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	379.39	Formula	C₂₀H₁₈FN₅O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	934343-74-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=C2C(=NC(=N1)N)CC(NC2=O)C3=C(C=C(C=C3)F)C4=NC(=CC=C4)OC

Solubility

In vitro
Batch:

DMSO : 76 mg/mL (200.32 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.
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.
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.
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.800mg/ml (10.02mM)	Taking the 1 mL working solution as an example, add 50 μL of 76 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.630mg/ml (1.66mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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.

Mechanism of Action

Features	NVP-HSP990 is an orally available HSP90 inhibitor and is structurally distinct from other clinical HSP90 inhibitors.
Targets/IC₅₀/Ki	HSP90α ^[1] (Cell-free assay) 0.6 nM HSP90β ^[1] (Cell-free assay) 0.8 nM
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] It displays dose- and time-dependent effects on HSP90 client proteins and 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 the compound 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]
Kinase Assay	HSP90 binding, ATPase, and selectivity profiling assays
Kinase Assay	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.
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]
References	[1] https://pubmed.ncbi.nlm.nih.gov/22246440/ [2] https://pubmed.ncbi.nlm.nih.gov/23492364/

Applications

Methods	Biomarkers	Images	PMID
Western blot	HSP90 / HSP70 EGFR / ErbB2 / ErbB3 / IGF-1R p-Akt / Akt / p-ERK / ERK / pp70S6K / p70S6K / p4EBP1 / 4EBP1		24100469

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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