Luminespib

Description

Hsp90 is a molecular chaperone of many different kinases, transcription factors, and hormone receptors involved in signal transduction, cell cycle regulation, and apoptosis. In addition to its important function in normal cell homeostasis, a high affinity form of Hsp90 is prevalent in tumor cells. Hsp90 inhibition has been associated with the degradation of oncogenic client proteins. NVP-AUY922 is a Hsp90 inhibitor (IC₅₀ = 21 nM in a FP binding assay) that prevents the proliferation of a range of human cancer cell lines in vitro with GI₅₀s averaging 9 nM. In a human colon cancer xenograft model, 50 mg/kg NVP-AUY922 inhibits tumor growth by ~50% compared to vehicle controls. Unlike some first generation Hsp90 inhibitors that are quickly glucuronidated, NVP-AUY922 is retained in tumors in vivo when administered at 4 mg/kg i.p. by cassette dosing in tumor-bearing mice.

The Uses of Luminespib

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. Potent Hedgehog inhibitor.

What are the applications of Application

NVP-AUY922 is a highly potent HSP90 inhibitor to HSP90α and HSP90β

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.

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