Luminespib | HSP90 inhibitor

Luminespib (747412-493) is a potent inhibitor (IC₅₀ = 21 nM) of HSP90.¹ It is active against various human tumor xenograft models acting via several processes including cytostasis, apoptosis, invasion, and angiogenesis.^2,3 Luminespib enhances tumor susceptibility to T-cell-based immunotherapy by re-invigorating the cancer-immunity cycle in NANOG⁺ cancer cells.⁴ It also acts as a radiosensitizer against various tumor cells.^5-7

References/Citations:

1. Brough et al. (2008), 4,5-Diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer; J. Med. Chem. 51 196
2. 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
3. Massey et al. (2010), Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor; Cancer Ther. 5 1807
4. Song et al. (2020), HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors; Nat. Commun. 11 562
5. Schwab and Multhoff (2022), A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922; Front.  Oncol. 12 861266
6. Djuzenova et al. (2012), Hsp90 inhibitor NVP-AUY922 enhances radiation sensitivity of tumor cells lines under hypoxia; Cancer Biol. Ther. 13 425
7. Schilling et al. (2015), Sensitizing tumor cells to radiation by targeting the heat shock response; Cancer Lett. 360 294