All AbMole products are for research use only, cannot be used for human consumption.
NVP-HSP990 is an orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively. NVP-HSP990 has potential antineoplastic activity.
In vitro, NVP-HSP990 exhibits single digit nanomolar IC(50) values on three of the Hsp90 isoforms (Hsp90α, Hsp90β, and GRP94) and 320 nanomolar IC(50) value on the fourth (TRAP-1), with selectivity against unrelated enzymes, receptors, and kinases. In c-Met amplified GTL-16 gastric tumor cells, NVP-HSP990 dissociated the Hsp90-p23 complex, depleted client protein c-Met, and induced Hsp70. NVP-HSP990 potently inhibited the growth of human cell lines and primary patient samples from a variety of tumor types.
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. On the basis of its pharmacologic profile and broad-spectrum antitumor activities, clinical trials have been initiated to evaluate NVP-HSP990 in advanced solid tumors.
Patent: US20230218577A1 2023 Jul.
Use of heat shock protein inhibitors for the treatment of neurodevelopmental disorders
NVP-HSP990 purchased from AbMole
Patent. US2023218577A1 2023 Jul 13.
Patent. US2023218577A1
NVP-HSP990 purchased from AbMole
 |
Source | Mol Cancer Ther (2012). Figure 1. NVP-HSP990 |
| Method | immunoprecipitation | |
| Cell Lines | GTL-16 cell line | |
| Concentrations | 250 nmol/L | |
| Incubation Time | 72 h | |
| Results | 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. Acocrystal structure solved to 1.5A resolution (manuscript in preparation) shows that NVP-HSP990 binds to the Nterminal ATP-binding domain of Hsp90. |
| Cell Experiment | |
|---|---|
| Cell lines | GTL-16, BT-474, A549, NCI-H1975 and MV4;11 cell lines |
| Preparation method | Cell proliferation and apoptosis assays Cells were treated with NVP-HSP990 or 17-AAG for 72 hours, and cell viability was determined by CellTiter-Glo Luminescent Cell Viability assay from Promega. Soft agar clonogenic assays with primary human tumors were conducted at Oncotest GmbH |
| Concentrations | 0~1000nM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | Human tumor xenograft models GTL-16, NCI-H1975, BT474, and MV4;11 |
| Formulation | 100% polyethylene glycol (PEG400) |
| Dosages | a single dose of 15 mg/kg |
| Administration | orally |
| Molecular Weight | 379.39 |
| Formula | C20H18FN5O2 |
| CAS Number | 934343-74-5 |
| Solubility (25°C) | DMSO 33 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related HSP Products |
|---|
| BIIB021
BIIB021 (CNF2024) is an orally available synthetic non-ansamycin Hsp90 inhibitor with ki value of 1.7nM. |
| CUDC-305
CUDC-305 is a heat shock protein 90 (HSP90) inhibitor of the novel imidazopyridine class, with IC50 values of 100 and 103 nM for HSP90α and HSP90β, respectively. |
| Ganetespib
Ganetespib (STA-9090) is a potent synthetic small molecule inhibitor of Hsp90 with potential antineoplastic activity. |
| Luminespib (AUY922)
Luminespib (AUY922) is a small molecule Heat Shock Protein 90 (HSP90) inhibitor with IC50 values of 13 and 21 nM for HSP90α and HSP90β respectively. |
| VER-82576
VER-82576 (NVP-BEP800) is a potent, orally available and selective inhibitor of Hsp90β with an IC50 of 58 nM. VER-82576 also slightly blocks Grp94 and Trap-1, with IC50s of 4.1 and 5.5 μM, respectively. |
All AbMole products are for research use only, cannot be used for human consumption or veterinary use. We do not provide products or services to individuals. Please comply with the intended use and do not use AbMole products for any other purpose.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2026 AbMole BioScience. All Rights Reserved.
