WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200371
Description: Luminespib, also known as AUY-922, NVP-AUY922, VER52296, is a derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Hsp90 inhibitor AUY922 has been shown to bind with high affinity to and inhibit Hsp90, resulting in the proteasomal degradation of oncogenic client proteins; the inhibition of cell proliferation; and the elevation of heat shock protein 72 (Hsp72) in a wide range of human tumor cell lines.
MedKoo Cat#: 200371
Name: Luminespib (AUY-922 )
Chemical Formula: C26H31N3O5
Exact Mass: 465.22637
Molecular Weight: 465.54
Elemental Analysis: C, 67.08; H, 6.71; N, 9.03; O, 17.18
Synonym: AUY922; AUY-922; AUY 922; NVP AUY922; NVP AUY-922; VER52296 ; VER-52296 ; VER 52296 ; Luminespib
IUPAC/Chemical Name: 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide
InChi Key: NDAZATDQFDPQBD-UHFFFAOYSA-N
InChi Code: 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 Code: O=C(C1=NOC(C2=CC(C(C)C)=C(O)C=C2O)=C1C3=CC=C(CN4CCOCC4)C=C3)NCC
Appearance: White to light yello solid powder
Purity: >98% (or refer to the Certificate of Analysis)
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).
HS Tariff Code: 2934.99.9001
|Biological target:||Luminespib is a HSP90 inhibitor with IC50s of 7.8 and 21 nM for HSP90α and HSP90β, respectively.|
|In vitro activity:||The effect of AUY922 on cell viability was measured by MTS assay. As shown in Figure 2b, AUY922 reduced cell viability in a dose- and time-dependent manner in four of five HCC (hepatocellular carcinoma) cell lines (Fig. 2b), but it showed no cytotoxicity in normal human primary hepatocytes (Fig. 2c). The 50% inhibitory concentration (IC50) values ranged from 9.2 to 16.2 μM in Huh7 and Hep3B cells, respectively, at 72 h (Supporting Information Table S4), whereas a minimal effect on SNU475 cells was observed, even at the highest dose tested (200 nM). Reference: Int J Cancer. 2019 May 15;144(10):2613-2624. https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31963|
|In vivo activity:||The potential therapeutic effects of AUY922 were tested in vivo using nude mice bearing HCC (hepatocellular carcinoma) tumor xenografts. AUY922 treatment led to significantly reduced tumor volume compared to the vehicle alone (Fig. 6a). Moreover, mice treated with AUY922 did not show significantly altered body weight when compared to control group, suggesting that the treatment was well tolerated (Fig. 6b). In addition, HSP90 inhibition was associated with significantly increased HSP70 expression in post-treatment HCC samples (Fig. 6c), confirming that AUY922 inhibited HSP90 activity in vivo (Fig. 2d). Reference: Int J Cancer. 2019 May 15;144(10):2613-2624. https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31963|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 465.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Augello G, Emma MR, Cusimano A, Azzolina A, Mongiovì S, Puleio R, Cassata G, Gulino A, Belmonte B, Gramignoli R, Strom SC, McCubrey JA, Montalto G, Cervello M. Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma. Int J Cancer. 2019 May 15;144(10):2613-2624. doi: 10.1002/ijc.31963. Epub 2018 Dec 24. PMID: 30488605. 2. Chittoor-Vinod VG, Bazick H, Todd AG, Falk D, Morelli KH, Burgess RW, Foster TC, Notterpek L. HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice. ACS Chem Neurosci. 2019 Jun 19;10(6):2890-2902. doi: 10.1021/acschemneuro.9b00105. Epub 2019 May 3. PMID: 31017387; PMCID: PMC6588339.|
|In vitro protocol:||1. Augello G, Emma MR, Cusimano A, Azzolina A, Mongiovì S, Puleio R, Cassata G, Gulino A, Belmonte B, Gramignoli R, Strom SC, McCubrey JA, Montalto G, Cervello M. Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma. Int J Cancer. 2019 May 15;144(10):2613-2624. doi: 10.1002/ijc.31963. Epub 2018 Dec 24. PMID: 30488605. 2. Chittoor-Vinod VG, Bazick H, Todd AG, Falk D, Morelli KH, Burgess RW, Foster TC, Notterpek L. HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice. ACS Chem Neurosci. 2019 Jun 19;10(6):2890-2902. doi: 10.1021/acschemneuro.9b00105. Epub 2019 May 3. PMID: 31017387; PMCID: PMC6588339.|
|In vivo protocol:||1. Augello G, Emma MR, Cusimano A, Azzolina A, Mongiovì S, Puleio R, Cassata G, Gulino A, Belmonte B, Gramignoli R, Strom SC, McCubrey JA, Montalto G, Cervello M. Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma. Int J Cancer. 2019 May 15;144(10):2613-2624. doi: 10.1002/ijc.31963. Epub 2018 Dec 24. PMID: 30488605. 2. Chittoor-Vinod VG, Bazick H, Todd AG, Falk D, Morelli KH, Burgess RW, Foster TC, Notterpek L. HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice. ACS Chem Neurosci. 2019 Jun 19;10(6):2890-2902. doi: 10.1021/acschemneuro.9b00105. Epub 2019 May 3. PMID: 31017387; PMCID: PMC6588339.|
1: Gaykema SB, SchrÃ¶der CP, Vitfell-Rasmussen J, Chua S, Oude Munnink TH, Brouwers AH, Bongaerts AH, Akimov M, Fernandez-Ibarra C, Lub-de Hooge MN, de Vries EG, Swanton C, Banerji U. 89Zr-trastuzumab and 89Zr-bevacizumab PET to Evaluate the Effect of the HSP90 Inhibitor NVP-AUY922 in Metastatic Breast Cancer Patients. Clin Cancer Res. 2014 Aug 1;20(15):3945-54. doi: 10.1158/1078-0432.CCR-14-0491. PubMed PMID: 25085789.
2: Doi T, Onozawa Y, Fuse N, Yoshino T, Yamazaki K, Watanabe J, Akimov M, Robson M, Boku N, Ohtsu A. Phase I dose-escalation study of the HSP90 inhibitor AUY922 in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Sep;74(3):629-36. doi: 10.1007/s00280-014-2521-x. Epub 2014 Jul 25. PubMed PMID: 25059319; PubMed Central PMCID: PMC4143601.
3: Chiang NJ, Wu SN, Kao CA, Huang YM, Chen LT. Stimulation of Electroporation-Induced Inward Currents in Glioblastoma Cell Lines by the Heat Shock Protein Inhibitor AUY922. Clin Exp Pharmacol Physiol. 2014 Jun 7. doi: 10.1111/1440-1681.12273. [Epub ahead of print] PubMed PMID: 24909268.
4: Huang J, Sun C, Zhang T, Pan L, Wang S, He Q, Li D. Potent antitumor activity of HSP90 inhibitor AUY922 in adrenocortical carcinoma. Tumour Biol. 2014 May 22. [Epub ahead of print] PubMed PMID: 24850175.
5: Chen SM, Guo CL, Shi JJ, Xu YC, Chen Y, Shen YY, Su Y, Ding J, Meng LH. HSP90 inhibitor AUY922 abrogates up-regulation of RTKs by mTOR inhibitor AZD8055 and potentiates its antiproliferative activity in human breast cancer. Int J Cancer. 2014 Apr 7. doi: 10.1002/ijc.28880. [Epub ahead of print] PubMed PMID: 24706460.
6: Zitzmann K, Ailer G, Vlotides G, Spoettl G, Maurer J, GÃ¶ke 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.
7: Voruganti S, Lacroix JC, Rogers CN, Rogers J, Matts RL, Hartson SD. The anticancer drug AUY922 generates a proteomics fingerprint that is highly conserved among structurally diverse Hsp90 inhibitors. J Proteome Res. 2013 Aug 2;12(8):3697-706. doi: 10.1021/pr400321x. Epub 2013 Jun 27. PubMed PMID: 23763277; PubMed Central PMCID: PMC3784992.
8: Sessa C, Shapiro GI, Bhalla KN, Britten C, Jacks KS, Mita M, Papadimitrakopoulou V, Pluard T, Samuel TA, Akimov M, Quadt C, Fernandez-Ibarra C, Lu H, Bailey S, Chica S, Banerji U. First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. Clin Cancer Res. 2013 Jul 1;19(13):3671-80. doi: 10.1158/1078-0432.CCR-12-3404. Epub 2013 Jun 11. PubMed PMID: 23757357.
9: Garon EB, Finn RS, Hamidi H, Dering J, Pitts S, Kamranpour N, Desai AJ, Hosmer W, Ide S, Avsar E, Jensen MR, Quadt C, Liu M, Dubinett SM, Slamon DJ. The HSP90 inhibitor NVP-AUY922 potently inhibits non-small cell lung cancer growth. Mol Cancer Ther. 2013 Jun;12(6):890-900. doi: 10.1158/1535-7163.MCT-12-0998. Epub 2013 Mar 14. PubMed PMID: 23493311; PubMed Central PMCID: PMC3681857.
10: Wainberg ZA, Anghel A, Rogers AM, Desai AJ, Kalous O, Conklin D, Ayala R, O'Brien NA, Quadt C, Akimov M, Slamon DJ, Finn RS. Inhibition of HSP90 with AUY922 induces synergy in HER2-amplified trastuzumab-resistant breast and gastric cancer. Mol Cancer Ther. 2013 Apr;12(4):509-19. doi: 10.1158/1535-7163.MCT-12-0507. Epub 2013 Feb 8. PubMed PMID: 23395886.
11: Gandhi N, Wild AT, Chettiar ST, Aziz K, Kato Y, Gajula RP, Williams RD, Cades JA, Annadanam A, Song D, Zhang Y, Hales RK, Herman JM, Armour E, DeWeese TL, Schaeffer EM, Tran PT. Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells. Cancer Biol Ther. 2013 Apr;14(4):347-56. doi: 10.4161/cbt.23626. Epub 2013 Jan 28. PubMed PMID: 23358469; PubMed Central PMCID: PMC3667875.
12: Walsby EJ, Lazenby M, Pepper CJ, Knapper S, Burnett AK. The HSP90 inhibitor NVP-AUY922-AG inhibits the PI3K and IKK signalling pathways and synergizes with cytarabine in acute myeloid leukaemia cells. Br J Haematol. 2013 Apr;161(1):57-67. doi: 10.1111/bjh.12215. Epub 2013 Jan 29. PubMed PMID: 23356405.
13: Hartmann S, GÃ¼nther N, Biehl M, Katzer A, Kuger S, Worschech E, Sukhorukov VL, Krohne G, Zimmermann H, Flentje M, Djuzenova CS. Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines. Cancer Lett. 2013 May 1;331(2):200-10. doi: 10.1016/j.canlet.2012.12.027. Epub 2013 Jan 20. PubMed PMID: 23340178.
14: Hsueh YS, Yen CC, Shih NY, Chiang NJ, Li CF, Chen LT. Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors. Autophagy. 2013 Feb 1;9(2):220-33. doi: 10.4161/auto.22802. Epub 2012 Nov 29. PubMed PMID: 23196876; PubMed Central PMCID: PMC3552885.
15: Armstrong H, Wolmarans A, Mercier R, Mai B, LaPointe P. The co-chaperone Hch1 regulates Hsp90 function differently than its homologue Aha1 and confers sensitivity to yeast to the Hsp90 inhibitor NVP-AUY922. PLoS One. 2012;7(11):e49322. doi: 10.1371/journal.pone.0049322. Epub 2012 Nov 14. PubMed PMID: 23166640; PubMed Central PMCID: PMC3498168.
16: Niewidok N, Wack LJ, Schiessl S, Stingl L, Katzer A, Polat B, Sukhorukov VL, Flentje M, Djuzenova CS. Hsp90 Inhibitors NVP-AUY922 and NVP-BEP800 May Exert a Significant Radiosensitization on Tumor Cells along with a Cell Type-Specific Cytotoxicity. Transl Oncol. 2012 Oct;5(5):356-69. Epub 2012 Oct 1. PubMed PMID: 23066444; PubMed Central PMCID: PMC3470116.
17: Bao XH, Takaoka M, Hao HF, Fukazawa T, Yamatsuji T, Sakurama K, Takigawa N, Nakajima M, Fujiwara T, Naomoto Y. Antiproliferative effect of the HSP90 inhibitor NVP-AUY922 is determined by the expression of PTEN in esophageal cancer. Oncol Rep. 2013 Jan;29(1):45-50. doi: 10.3892/or.2012.2074. Epub 2012 Oct 9. PubMed PMID: 23064324.
18: Okui T, Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A. Novel HSP90 inhibitor NVP-AUY922 enhances the anti-tumor effect of temsirolimus against oral squamous cell carcinoma. Curr Cancer Drug Targets. 2013 Mar;13(3):289-99. PubMed PMID: 23016912.
19: Moser C, Lang SA, Hackl C, Wagner C, Scheiffert E, Schlitt HJ, Geissler EK, Stoeltzing O. Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer. Anticancer Res. 2012 Jul;32(7):2551-61. PubMed PMID: 22753713.
20: Best OG, Mulligan SP. Heat shock protein-90 inhibitor, NVP-AUY922, is effective in combination with fludarabine against chronic lymphocytic leukemia cells cultured on CD40L-stromal layer and inhibits their activated/proliferative phenotype. Leuk Lymphoma. 2012 Nov;53(11):2314-20. doi: 10.3109/10428194.2012.698278. Epub 2012 Jul 9. PubMed PMID: 22646928.
NVP-AUY922 is a novel resorcinylic isoxazole amide heat shock protein 90 (HSP90) inhibitor. NVP-AUY922 potently inhibits HSP90 (Kd = 1.7 nmol/L) and proliferation of human tumor cells with GI50 values of approximately 2 to 40 nmol/L, inducing G1-G2 arrest and apoptosis. Activity is independent of NQO1/DT-diaphorase, maintained in drug-resistant cells and under hypoxic conditions. The molecular signature of HSP90 inhibition, comprising induced HSP72 and depleted client proteins, was readily demonstrable. NVP-AUY922 was glucuronidated less than previously described isoxazoles, yielding higher drug levels in human cancer cells and xenografts. Daily dosing of NVP-AUY922 (50 mg/kg i.p. or i.v.) to athymic mice generated peak tumor levels at least 100-fold above cellular GI50. This produced statistically significant growth inhibition and/or regressions in human tumor xenografts with diverse oncogenic profiles: BT474 breast tumor treated/control, 21%; A2780 ovarian, 11%; U87MG glioblastoma, 7%; PC3 prostate, 37%; and WM266.4 melanoma, 31%. Therapeutic effects were concordant with changes in pharmacodynamic markers, including induction of HSP72 and depletion of ERBB2, CRAF, cyclin-dependent kinase 4, phospho-AKT/total AKT, and hypoxia-inducible factor-1α, determined by Western blot, electrochemiluminescent immunoassay, or immunohistochemistry. NVP-AUY922 also significantly inhibited tumor cell chemotaxis/invasion in vitro, WM266.4 melanoma lung metastases, and lymphatic metastases from orthotopically implanted PC3LN3 prostate carcinoma. NVP-AUY922 inhibited proliferation, chemomigration, and tubular differentiation of human endothelial cells and antiangiogenic activity was reflected in reduced microvessel density in tumor xenografts. Collectively, the data show that NVP-AUY922 is a potent, novel inhibitor of HSP90, acting via several processes (cytostasis, apoptosis, invasion, and angiogenesis) to inhibit tumor growth and metastasis. NVP-AUY922 has entered phase I clinical trials. [ source: Cancer Res 2008;68(8):2850Â–60].