NVP-HSP990
Based on 4 publication(s) in Google Scholar
NVP-HSP990 is a potent, selective and orally active Hsp90 inhibitor, with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively.
For research use only. We do not sell to patients.
- Purity: 99.49%
- CAS No.: 934343-74-5
- Formula: C20H18FN5O2
- Molecular Weight:379.39
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) NVP-HSP990
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Biological Activity
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HSP90α 0.6 nM (IC50) |
HSP90β 0.8 nM (IC50) |
GRP94 8.5 nM (IC50) |
TRAP1 ATPase 320 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2058 | IC50 |
12.7 nM
Compound: NVP-HSP990
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Cytotoxicity against human A2058 cells in absence of HSF1 knock down treatment
Cytotoxicity against human A2058 cells in absence of HSF1 knock down treatment
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[PMID: 26164188] |
| A2058 | IC50 |
5.2 nM
Compound: NVP-HSP990
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Cytotoxicity against human A2058 cells in presence of HSF1 knock down treatment
Cytotoxicity against human A2058 cells in presence of HSF1 knock down treatment
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[PMID: 26164188] |
| A-375 | IC50 |
19 nM
Compound: NVP-HSP990
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Cytotoxicity against human A375 cells in absence of HSF1 knock down treatment
Cytotoxicity against human A375 cells in absence of HSF1 knock down treatment
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[PMID: 26164188] |
| A-375 | IC50 |
6 nM
Compound: NVP-HSP990
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Cytotoxicity against human A375 cells in presence of HSF1 knock down treatment
Cytotoxicity against human A375 cells in presence of HSF1 knock down treatment
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[PMID: 26164188] |
| GTL 16 cell line | EC50 |
0.014 μM
Compound: 9
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Cytotoxicity against human GTL16 cells after 72 hrs by CellTitre-Glo assay
Cytotoxicity against human GTL16 cells after 72 hrs by CellTitre-Glo assay
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[PMID: 25368984] |
NVP-HSP990 is a potent and selective Hsp90 inhibitor, with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively. NVP-HSP990 (10 μM) shows no affect the ATPase activity of topoisomerase II, a GHKL (Gyrase, Hsp90, Histidine Kinase, MutL) family ATPase, closely related to Hsp90. NVP-HSP990 also exerts efficient effects on c-Met, Hsp70, p-ERK and p-AKT in CTL-16 cells, with EC50s of 37 ± 4, 20 ± 2, 11 ± 1, and 6 ± 1 nM, respectively. NVP-HSP990 suppresses the proliferation of BT474, A549, H1975 and MV4;11 cells, with GI50s of 7 ± 2, 28 ± 5, 35 ± 4, and 4 ± 1 nM, respectively[1]. NVP-HSP990 inhibits cellular proliferation of GTL-16, with an EC50 of 14 nM[2]. NVP-HSP990 (5-500 nM) inhibits the multiple myeloma cell lines, with IC50s of 27-49 nM after treatment for 72 h. NVP-HSP990 induces apoptosis in multiple myeloma cell lines (0-100 nM), leads to cell cycle arrest in the G2/M phase (25-200 nM), and induces apoptosis via caspase-8 followed by caspase-3 activation (100 nM). NVP-HSP990 increases HSP70 expression and interacts with Akt and ERK signaling. Moreover, NVP-HSP990 (100 nM) in combination with melphalan, causes synergistic effects on growth inhibition in multiple myeloma cells and increases cleavage of caspase-3, caspase-8, and caspase-9 and activates caspase-2[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 934343-74-5
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Appearance Solid
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Molecular Weight 379.39
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Formula C20H18FN5O2
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Color Off-white to yellow
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SMILES
CC1=C2C(C[C@H](C3=C(C4=NC(OC)=CC=C4)C=C(F)C=C3)NC2=O)=NC(N)=N1
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Synonyms
HSP-990
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (4)
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Journal Impact Factor
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Most Recent
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Theranostics
Inhibition of HSP90β Improves Lipid Disorders by Promoting Mature SREBPs Degradation via the Ubiquitin-proteasome System. [Abstract]2019 Aug 12;9(20):5769-5783. PMID: 31534518 -
Front Microbiol
Ketoconazole induces reversible antifungal drug tolerance mediated by trisomy of chromosome R in Candida albicans. [Abstract]2024 Jul 30:15:1450557. PMID: 39139375 -
Viruses
Deep Transfer Learning Approach for Automatic Recognition of Drug Toxicity and Inhibition of SARS-CoV-2. [Abstract]2021 Apr 2;13(4):610. PMID: 33918368 -
Solvent & Solubility
DMSO : ≥ 33 mg/mL (86.98 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.48 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
His-tagged Hsp90α N-terminal domain protein (N-Hsp90α-His) is diluted to 2× the final concentration in the assay buffer consisting of 50 mM Hepes, pH 7, 6 mM MgCl2, 20 mM KCl and 0.1% BSA. The Hsp90 is dispensed into 96 well polypropylene plates at 50 µL per well. In a separate polypropylene plate, test compounds (NVP-HSP990) are diluted to 40× their final concentration in 100% DMSO. Serial dilutions in DMSO are made in 3-fold increments. 2.5 µL of diluted compounds are transferred to the 50 µL of Hsp90 and mixed. Background wells receive 25 µM (final concentration) radicicol. Biotin-radicicol is diluted into assay buffer at 2× the final concentration and 50 µL are added to the Hsp90/compound plate. DMSO is at a final concentration of 2.5%. Samples are incubated at room temperature for 2 hours before 50 µL are transferred to NeutrAvidin-coated plates. Plates are incubated 1 hour, washed 3× with DELFIA wash buffer (5 mM Tris, pH 7.5, 0.1% Tween 20, 0.1% sodium azide, 0.9% NaCl), and then 50 µL per well of 3 nM Eu-anti-His diluted into DELFIA assay buffer are added. The plates are next incubated 2 hours at room temperature, washed 4×, and then 50 µL enhancement solution are added. Plates are gently shaken for 7-10 minutes before reading in a VICTOR2 instrument[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GTL-16 Cells (1 × 103) are plated into 96 well tissue culture plates and cultured at 37°C, 5% CO2. Serially diluted compounds (NVP-HSP990) are added to the cells and are incubated for 72 hrs. at 37°C, 5% CO2. Cell proliferation is determined using Cell Viability assay[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Human tumor xenograft models GTL-16, NCI-H1975, BT474, and MV4;11 are implanted subcutaneously with 50% Matrigel in nude or severe combined immunodeficient mice. Mice are randomized into cohorts (10 mice/group for efficacy) when tumors reach 200 to 500 mm3. NVP-HSP990 is administered orally in a vehicle of 100% polyethylene glycol (PEG400). Tumor caliper measurements are converted into tumor volumes using the formula: [length × (width)2]/2. Relative tumor inhibition is calculated as %T/C = 100 × dT/dC, where, dT or dC = difference of mean tumor volume of drug treatment (T) or vehicle (C) on the final day of the study and the randomization volume. Statistical comparisons are conducted using a one-way ANOVA, followed by the Dunn or Tukey post hoc test. Differences are statistically significant at P < 0.05[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
[1]. Menezes DL, et al. The novel oral Hsp90 inhibitor NVP-HSP990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. Mol Cancer Ther. 2012 Mar;11(3):730-9. [Content Brief]
[2]. McBride CM, et al. Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990. J Med Chem. 2014 Nov 13;57(21):9124-9. [Content Brief]
[3]. Lamottke B, et al. The novel, orally bioavailable HSP90 inhibitor NVP-HSP990 induces cell cycle arrest and apoptosis in multiple myeloma cells and acts synergistically with melphalan by increased cleavage of caspases. Eur J Haematol. 2012 May;88(5):406-15. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6358 mL | 13.1791 mL | 26.3581 mL | 65.8953 mL |
| 5 mM | 0.5272 mL | 2.6358 mL | 5.2716 mL | 13.1791 mL | |
| 10 mM | 0.2636 mL | 1.3179 mL | 2.6358 mL | 6.5895 mL | |
| 15 mM | 0.1757 mL | 0.8786 mL | 1.7572 mL | 4.3930 mL | |
| 20 mM | 0.1318 mL | 0.6590 mL | 1.3179 mL | 3.2948 mL | |
| 25 mM | 0.1054 mL | 0.5272 mL | 1.0543 mL | 2.6358 mL | |
| 30 mM | 0.0879 mL | 0.4393 mL | 0.8786 mL | 2.1965 mL | |
| 40 mM | 0.0659 mL | 0.3295 mL | 0.6590 mL | 1.6474 mL | |
| 50 mM | 0.0527 mL | 0.2636 mL | 0.5272 mL | 1.3179 mL | |
| 60 mM | 0.0439 mL | 0.2197 mL | 0.4393 mL | 1.0983 mL | |
| 80 mM | 0.0329 mL | 0.1647 mL | 0.3295 mL | 0.8237 mL |
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