Luminespib

Luminespib
Names
	IUPAC name 5-(2,4-Dihydroxy-5-isopropyl-phenyl)-N-ethyl-4-[4-(morpholinomethyl)phenyl]isoxazole-3-carboxamide
	Other names NVP-AUY-922; AUY922; VER-52296
Identifiers
CAS Number	747412-49-3 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:83656 ;
ChEMBL	ChEMBL252164 ;
ChemSpider	21377936 ;
DrugBank	DB11881;
KEGG	D10646 ;
PubChem CID	135539077;
UNII	C6V1DAR5EB;
	InChI 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) Key: NDAZATDQFDPQBD-UHFFFAOYSA-N ; 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);
	SMILES CC(C)c1cc(c(O)cc1O)c2onc(C(=O)NCC)c2c3ccc(cc3)CN4CCOCC4;
Properties
Chemical formula	C26H31N3O5
Molar mass	465.550 g·mol−1
Appearance	Colorless solid[1]
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

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]

References

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.
"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.
"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.
"AUY922". Vernalis. Archived from the original on 2011-09-29.
"Small caps: Vernalis drug fillip". Financial Times. July 19, 2011.
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.
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.
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.
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.
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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[Brough-1] 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.

[Sidera2014rev-6] 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.

Luminespib

See also

References