| Identification | Back Directory | [Name]
5-[2,4-Dihydroxy-5-isopropylphenyl]-N-ethyl-4-[4-(4-morpholinylmethyl)phenyl]-3-isoxazolecarboxamide | [CAS]
747412-49-3 | [Synonyms]
AUY 922
VER 52296
VER-52296
LuMinespib
NVP-AUY922
AUY922, VER-52296
NVP-AUY922, >=98%
AUY922 (NVP-AUY922)
Luminespib (NVP-AUY922)
AUY922,NVP-AUY-922,Luminespib
NVP-AUY922, Luminespib, VER52296
Luminespib (AUY-922, NVP-AUY922)
5-(2,4-Dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxam
5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide
5-[2,4-Dihydroxy-5-isopropylphenyl]-N-ethyl-4-[4-(4-morpholinylmethyl)phenyl]-3-isoxazolecarboxamide
5-[2,4-Dihydroxy-5-isopropylphenyl]-N-ethyl-4-[4-(4-morpholinylmethyl)phenyl]-3-isoxazolecarboxamide AUY922 (NVP-AUY922) | [Molecular Formula]
C26H31N3O5 | [MDL Number]
MFCD14635361 | [MOL File]
747412-49-3.mol | [Molecular Weight]
465.547 |
| Chemical Properties | Back Directory | [Melting point ]
180-184°C | [Boiling point ]
640.1±55.0 °C(Predicted) | [density ]
1.234 | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
solid | [pka]
8.47±0.48(Predicted) | [color ]
White | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months. | [CAS DataBase Reference]
747412-49-3 |
| Hazard Information | Back Directory | [Uses]
NVP-AUY 922 is a potent inhibitor of heat shock protein 90 (Hsp90) that prevents the proliferation of a range of human cancer cell lines. NVP-AUY 922 has been shown to enhance the radiation sensitivity of tumor cell lines under hypoxia. | [Definition]
ChEBI: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxylic acid with the amino group of ethylamine. | [target]
HSP90α | [storage]
Store at -20°C | [References]
Brough et al. (2008), 4,5-Diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer; Med. Chem. 51 196
Eccles et al. (2008), NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis; Cancer Res. 68 2850
Massey et al. (2010), Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor; Cancer Ther. 5 1807
Song et al. (2020), HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors; Commun. 11 562
Schwab and Multhoff (2022), A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922; Oncol. 12 861266
Djuzenova et al. (2012), Hsp90 inhibitor NVP-AUY922 enhances radiation sensitivity of tumor cells lines under hypoxia; Cancer Biol. Ther. 13 425
Schilling et al. (2015), Sensitizing tumor cells to radiation by targeting the heat shock response; Cancer Lett. 360 294 |
| Questions And Answer | Back Directory | [Description]
Luminespib (AUY-922, NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Phase 2. | [In vitro]
NVP-AUY922 inhibits proliferation of various human cancer cell lines in vitro, with an average GI50 of 9 nM. The IC50 values of NVP-AUY922 fall in the range of 2 to 40 nM in these gastric cancer cell lines. IC50 value for the BEAS-2B cells is 28.49 nM. Treatment with NVP-AUY922 does not influence the expression of HSP90, but expression of HSP70 gets elevated by NVP-AUY922 treatment. NVP-AUY922 increases the binding of HSP70 to HSP90. NVP-AUY922 causes p23 dissociation from the HSP90 complex and can then recruit HSP70 to the HSP90 complex. After the treatment with NVP-AUY922, expression of receptor tyrosine kinases including VEGFR1, 2, 3 and PDGFRɑ is decreased. A decrease is also noticed in the expression of Akt and phospho-Akt. Meanwhile, treatment with NVP-AUY922 causes decreased expression of HER-2 in NCI-N87 cells. NVP-AUY922 treatment results in binding of HSP90 to client proteins and setting them up as targets for degradation by the proteasome. NVP-AUY922 can influence cell growth by affecting multiple signaling pathways. In addition, treatment with the proteasome inhibitor, MG132, restores expression of thymidylate synthase, which is decreased by NVP-AUY922. NVP-AUY922 increases the expression of cleaved caspase-3 leading to apoptosis in HSC-2 cells. | [In vivo]
Treatment with NVP-AUY922 causes a robust antitumor response and inhibits p-Akt and VEGF expression in an HSC-2 xenograft model. In BT474, NVP-AUY922 shows complete loss of ERBB2 and substantial depletion of ERα, in addition to reductions in CDK4 and phospho-ERK1/2. |
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