Luminespib

Last updated
Luminespib
Luminespib.svg
Names
Preferred IUPAC name
5-[2,4-Dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-{4-[(morpholin-4-yl)methyl]phenyl}-1,2-oxazole-3-carboxamide
Other names
NVP-AUY-922; AUY922; VER-52296
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
PubChem CID
UNII
  • InChI=1S/C26H31N3O5/c1-4-27-26(32)24-23(18-7-5-17(6-8-18)15-29-9-11-33-12-10-29)25(34-28-24)20-13-19(16(2)3)21(30)14-22(20)31/h5-8,13-14,16,30-31H,4,9-12,15H2,1-3H3,(H,27,32) Yes check.svgY
    Key: NDAZATDQFDPQBD-UHFFFAOYSA-N Yes check.svgY
  • InChI=1S/C26H31N3O5/c1-4-27-26(32)24-23(18-7-5-17(6-8-18)15-29-9-11-33-12-10-29)25(34-28-24)20-13-19(16(2)3)21(30)14-22(20)31/h5-8,13-14,16,30-31H,4,9-12,15H2,1-3H3,(H,27,32)
  • CC(C)c1cc(c(O)cc1O)c2onc(C(=O)NCC)c2c3ccc(cc3)CN4CCOCC4
Properties
C26H31N3O5
Molar mass 465.550 g·mol−1
AppearanceColorless solid [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Luminespib (INN, [2] previously known as NVP-AUY922) is an experimental drug candidate for the treatment of cancer. It was discovered through a collaboration between The Institute of Cancer Research and the pharmaceutical company Vernalis [3] and licensed to Novartis. [4] From 2011 to 2014 it was in Phase II clinical trials. [5] [6] Chemically it is a resorcinylic isoxazole amide [6]

Luminespib is an inhibitor of heat shock protein 90 (Hsp90), [1] which is a chaperone protein that plays a role in the modification of a variety of proteins that have been implicated in oncogenesis. Luminespib has shown promising activity in preclinical testing against several different tumor types. [7] [8] [9] [10]

A related compound, NVP-HSP990, was abandoned by Novartis in 2012 after it failed to show efficacy in an early clinical trial. [6]

See also

References

  1. 1 2 Brough, Paul A.; Aherne, Wynne; Barril, Xavier; Borgognoni, Jenifer; Boxall, Kathy; Cansfield, Julie E.; Cheung, Kwai-Ming J.; Collins, Ian; Davies, Nicholas G. M. (2008). "4,5-Diarylisoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer" . Journal of Medicinal Chemistry. 51 (2): 196–218. doi:10.1021/jm701018h. PMID   18020435.
  2. ↑ "WHO Drug Information. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 70" (PDF). World Health Organization. pp. 297–8. Retrieved 16 July 2016.
  3. ↑ "Structure-based design of cancer therapeutics" (PDF). The Institute of Cancer Research. Archived from the original (PDF) on 2011-06-25. Retrieved 2011-10-25.
  4. ↑ "AUY922". Vernalis. Archived from the original on 2011-09-29.
  5. ↑ "Small caps: Vernalis drug fillip". Financial Times. July 19, 2011.
  6. 1 2 3 Sidera, K.; Patsavoudi, E. (Jan 2014). "HSP90 inhibitors: current development and potential in cancer therapy". Recent Patents on Anti-Cancer Drug Discovery. 9 (1): 1–20. doi:10.2174/15748928113089990031. PMID   23312026.
  7. ↑ Jensen, Michael; Schoepfer, Joseph; Radimerski, Thomas; Massey, Andrew; Guy, Chantale T; Brueggen, Josef; Quadt, Cornelia; Buckler, Alan; Cozens, Robert (2008). "NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models". Breast Cancer Research. 10 (2): R33. doi: 10.1186/bcr1996 . PMC   2397535 . PMID   18430202.
  8. ↑ Gaspar, N.; Sharp, S. Y.; Eccles, S. A.; Gowan, S.; Popov, S.; Jones, C.; Pearson, A.; Vassal, G.; Workman, P. (2010). "Mechanistic Evaluation of the Novel HSP90 Inhibitor NVP-AUY922 in Adult and Pediatric Glioblastoma". Molecular Cancer Therapeutics. 9 (5): 1219–1233. doi:10.1158/1535-7163.MCT-09-0683. PMC   2875164 . PMID   20457619.
  9. ↑ Okui, T; Shimo, T; Hassan, NM; Fukazawa, T; Kurio, N; Takaoka, M; Naomoto, Y; Sasaki, A (2011). "Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma". Anticancer Research. 31 (4): 1197–204. PMID   21508365.
  10. ↑ Eccles, S. A.; Massey, A.; Raynaud, F. I.; Sharp, S. Y.; Box, G.; Valenti, M.; Patterson, L.; De Haven Brandon, A.; Gowan, S. (2008). "NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis". Cancer Research. 68 (8): 2850–2860. doi: 10.1158/0008-5472.CAN-07-5256 . PMID   18413753.


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