HSP990 is an orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp990 binds to and inhibits the activity of Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. Hsp90, upregulated in a variety of tumor cells, is a molecular chaperone that plays a key role in the conformational maturation, stability and function of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation and/or immune responses. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

MedKoo Cat#: 205487 Name: HSP-990 CAS#: 934343-74-5 Chemical Formula: C20H18FN5O2 Exact Mass: 379.14445 Molecular Weight: 379.39 Elemental Analysis: C, 63.32; H, 4.78; F, 5.01; N, 18.46; O, 8.43

Synonym: HSP990; HSP-990; HSP 990; NVP HSP 990; NVP-HSP990; NVP HSP-990;

IUPAC/Chemical Name: (R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one

InChi Key: WSMQUUGTQYPVPD-OAHLLOKOSA-N

InChi Code: InChI=1S/C20H18FN5O2/c1-10-18-16(26-20(22)23-10)9-15(25-19(18)27)12-7-6-11(21)8-13(12)14-4-3-5-17(24-14)28-2/h4-8,15H,9H2,1-2H3,(H,25,27)(H2,22,23,26)/t15-/m1/s1

SMILES Code: O=C1N[C@@H](C2=CC=C(F)C=C2C3=NC(OC)=CC=C3)CC4=NC(N)=NC(C)=C41

Technical Data

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Certificate of Analysis: View current batch of CoA

QC Data: View NMR, View HPLC, View MS

Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

References

1: Gillis JL, Selth LA, Centenera MM, Townley SL, Sun S, Plymate SR, Tilley WD, Butler LM. Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors. Oncotarget. 2013 May;4(5):691-704. PubMed PMID: 23674566.

2: Fu J, Koul D, Yao J, Wang S, Yuan Y, Colman H, Sulman EP, Lang FF, Yung WK. Novel HSP90 inhibitor NVP-HSP990 targets cell-cycle regulators to ablate Olig2-positive glioma tumor-initiating cells. Cancer Res. 2013 May 15;73(10):3062-74. doi: 10.1158/0008-5472.CAN-12-2033. Epub 2013 Mar 14. PubMed PMID: 23492364; PubMed Central PMCID: PMC3655088.

3: Milanović D, Firat E, Grosu AL, Niedermann G. Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990. Radiat Oncol. 2013 Feb 28;8:42. doi: 10.1186/1748-717X-8-42. PubMed PMID: 23448094; PubMed Central PMCID: PMC3599905.

4: Centenera MM, Gillis JL, Hanson AR, Jindal S, Taylor RA, Risbridger GP, Sutherland PD, Scher HI, Raj GV, Knudsen KE, Yeadon T; Australian Prostate Cancer BioResource, Tilley WD, Butler LM. Evidence for efficacy of new Hsp90 inhibitors revealed by ex vivo culture of human prostate tumors. Clin Cancer Res. 2012 Jul 1;18(13):3562-70. doi: 10.1158/1078-0432.CCR-12-0782. Epub 2012 May 9. PubMed PMID: 22573351.

5: Lamottke B, Kaiser M, Mieth M, Heider U, Gao Z, Nikolova Z, Jensen MR, Sterz J, von Metzler I, Sezer O. The novel, orally bioavailable HSP90 inhibitor NVP-HSP990 induces cell cycle arrest and apoptosis in multiple myeloma cells and acts synergistically with melphalan by increased cleavage of caspases. Eur J Haematol. 2012 May;88(5):406-15. doi: 10.1111/j.1600-0609.2012.01764.x. Epub 2012 Mar 21. PubMed PMID: 22309072.

6: Stühmer T, Iskandarov K, Gao Z, Bumm T, Grella E, Jensen MR, Einsele H, Chatterjee M, Bargou RC. Preclinical activity of the novel orally bioavailable HSP90 inhibitor NVP-HSP990 against multiple myeloma cells. Anticancer Res. 2012 Feb;32(2):453-62. PubMed PMID: 22287732.

7: Menezes DL, Taverna P, Jensen MR, Abrams T, Stuart D, Yu GK, Duhl D, Machajewski T, Sellers WR, Pryer NK, Gao Z. The novel oral Hsp90 inhibitor NVP-HSP990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. Mol Cancer Ther. 2012 Mar;11(3):730-9. doi: 10.1158/1535-7163.MCT-11-0667. Epub 2012 Jan 12. PubMed PMID: 22246440.

8: Khong T, Spencer A. Targeting HSP 90 induces apoptosis and inhibits critical survival and proliferation pathways in multiple myeloma. Mol Cancer Ther. 2011 Oct;10(10):1909-17. doi: 10.1158/1535-7163.MCT-11-0174. Epub 2011 Aug 22. PubMed PMID: 21859842.

9: Jackrel ME, Shorter J. Shock and awe: unleashing the heat shock response to treat Huntington disease. J Clin Invest. 2011 Aug;121(8):2972-5. doi: 10.1172/JCI59190. Epub 2011 Jul 25. PubMed PMID: 21785212; PubMed Central PMCID: PMC3148752.