HSP-990

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WARNING: This product is for research use only, not for human or veterinary use.

Description: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.

Price and Availability

HSP-990, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 205487Name: HSP-990CAS#: 934343-74-5Chemical Formula: C20H18FN5O2Exact Mass: 379.14445Molecular Weight: 379.39Elemental 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/h3-8,15H,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

Additional Information

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.

References

1: Spagnoletti G, Li Bergolis V, Piscazzi A, Giannelli F, Condelli V, Sisinni L,Bove G, Storto G, Landriscina M. Cyclin-dependent kinase 1 targeting improves sensitivity to radiation in BRAF V600E colorectal carcinoma cells. Tumour Biol. 2018 Apr;40(4):1010428318770957. doi: 10.1177/1010428318770957. PubMed PMID: 29663854.

2: Moriya C, Taniguchi H, Nagatoishi S, Igarashi H, Tsumoto K, Imai K. PRDM14 directly interacts with heat shock proteins HSP90α and glucose-regulated protein78. Cancer Sci. 2018 Feb;109(2):373-383. doi: 10.1111/cas.13458. Epub 2017 Dec 28. PubMed PMID: 29178343; PubMed Central PMCID: PMC5797828.

3: Lee SL, Dempsey-Hibbert NC, Vimalachandran D, Wardle TD, Sutton PA, Williams JH. Re-examining HSPC1 inhibitors. Cell Stress Chaperones. 2017 Mar;22(2):293-306. doi: 10.1007/s12192-017-0774-0. Epub 2017 Mar 2. PubMed PMID:28255900; PubMed Central PMCID: PMC5352602.

4: Palladino G, Notarangelo T, Pannone G, Piscazzi A, Lamacchia O, Sisinni L, Spagnoletti G, Toti P, Santoro A, Storto G, Bufo P, Cignarelli M, Esposito F, Landriscina M. TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells. Endocr Relat Cancer. 2016 Sep;23(9):699-709. doi: 10.1530/ERC-16-0063. Epub 2016 Jul 15. PubMed PMID: 27422900.

5: Li L, An M, Shen H, Huang X, Yao X, Liu J, Zhu F, Zhang S, Chen S, He L, Zhang J, Zou Z, Jiang Y. The non-Geldanamycin Hsp90 inhibitors enhanced the antifungalactivity of fluconazole. Am J Transl Res. 2015 Dec 15;7(12):2589-602. eCollection 2015. PubMed PMID: 26885259; PubMed Central PMCID: PMC4731659.

6: Spreafico A, Delord JP, De Mattos-Arruda L, Berge Y, Rodon J, Cottura E, Bedard PL, Akimov M, Lu H, Pain S, Kaag A, Siu LL, Cortes J. A first-in-human phase I, dose-escalation, multicentre study of HSP990 administered orally in adult patients with advanced solid malignancies. Br J Cancer. 2015 Feb 17;112(4):650-9. doi: 10.1038/bjc.2014.653. Epub 2015 Jan 27. PubMed PMID: 25625276; PubMed Central PMCID: PMC4333497.

7: Koul D, Yao J, Wan S, Yuan Y, Sulman E, Lang F, Yung WK, Colman H. Retraction: Novel HSP90 inhibitor NVP-HSP990 targets cell-cycle regulators to ablate Olig 2-positive glioma tumor-initiating cells. Cancer Res. 2014 Nov 15;74(22):6731-2.doi: 10.1158/0008-5472.CAN-14-2966. PubMed PMID: 25398854; PubMed Central PMCID:PMC4381954.

8: McBride CM, Levine B, Xia Y, Bellamacina C, Machajewski T, Gao Z, Renhowe P, Antonios-McCrea W, Barsanti P, Brinner K, Costales A, Doughan B, Lin X, Louie A,McKenna M, Mendenhall K, Poon D, Rico A, Wang M, Williams TE, Abrams T, Fong S, Hendrickson T, Lei D, Lin J, Menezes D, Pryer N, Taverna P, Xu Y, Zhou Y, ShaferCM. Design, structure-activity relationship, and in vivo characterization of thedevelopment candidate NVP-HSP990. J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q. Epub 2014 Nov 4. PubMed PMID: 25368984.

9: Condelli V, Piscazzi A, Sisinni L, Matassa DS, Maddalena F, Lettini G, SimeonV, Palladino G, Amoroso MR, Trino S, Esposito F, Landriscina M. TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell-cycle progression: a novel target for BRAF-mutated colorectal tumors. Cancer Res. 2014 Nov 15;74(22):6693-704. doi: 10.1158/0008-5472.CAN-14-1331. Epub 2014 Sep 19. PubMed PMID: 25239454.

10: Wachsberger PR, Lawrence YR, Liu Y, Rice B, Feo N, Leiby B, Dicker AP. Hsp90inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma.J Cancer Res Clin Oncol. 2014 Apr;140(4):573-82. doi: 10.1007/s00432-014-1594-6.Epub 2014 Feb 6. PubMed PMID: 24500492.

11: Aguilà M, Bevilacqua D, McCulley C, Schwarz N, Athanasiou D, Kanuga N, Novoselov SS, Lange CA, Ali RR, Bainbridge JW, Gias C, Coffey PJ, Garriga P, Cheetham ME. Hsp90 inhibition protects against inherited retinal degeneration. Hum Mol Genet. 2014 Apr 15;23(8):2164-75. doi: 10.1093/hmg/ddt613. Epub 2013 Dec2. PubMed PMID: 24301679; PubMed Central PMCID: PMC3959821.

12: Zitzmann K, Ailer G, Vlotides G, Spoettl G, Maurer J, Göke B, Beuschlein F, Auernhammer CJ. Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells. Int J Oncol. 2013 Dec;43(6):1824-32. doi: 10.3892/ijo.2013.2130. Epub 2013 Oct 4. PubMed PMID: 24100469; PubMed Central PMCID: PMC3834873.

13: 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; PubMed Central PMCID: PMC3742830.

14: 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. Retraction in: Koul D, Yao J, Wan S, Yuan Y, Sulman E, Lang F, Yung WK, Colman H. Cancer Res. 2014 Nov 15;74(22):6731-2. PubMed PMID: 23492364; PubMed Central PMCID: PMC3655088.

15: Milanović D, Firat E, Grosu AL, Niedermann G. Increased radiosensitivity andradiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma celllines 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.

16: 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 inhibitorsrevealed 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.

17: Lamottke B, Kaiser M, Mieth M, Heider U, Gao Z, Nikolova Z, Jensen MR, SterzJ, von Metzler I, Sezer O. The novel, orally bioavailable HSP90 inhibitor NVP-HSP990 induces cell cycle arrest and apoptosis in multiple myeloma cells andacts 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.

18: 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.

19: 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.

20: Khong T, Spencer A. Targeting HSP 90 induces apoptosis and inhibits criticalsurvival 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. PubMedPMID: 21859842.