MedKoo product information:

  AEW-541

Description of AEW-541: AEW541 (also known as NVP-AEW541) is an IGF-IR inhibitor with an IC50 of median 3.6 μM.

Current developer:    Novartis Pharmaceuticals

NVP-AEW541 is a pyrrolo[2,3-d]pyrimidine derivative small molecular weight kinase inhibitor of the IGF-IR, capable of distinguishing between the IGF-IR (IC50 = 0.086 microM) and the closely related InsR (IC50 = 2.3 microM) in cells. As expected for a specific IGF-IR kinase inhibitor, NVP-AEW541 abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. In vivo, this orally bioavailable compound inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas. Thus, NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application. (Source: García-Echeverría C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, Evans DB, Fabbro D, Furet P, Porta DG, Liebetanz J, Martiny-Baron G, Ruetz S, Hofmann F. Cancer Cell. 2004 Mar;5(3):231-9.) 

1: Isebaert SF, Swinnen JV, McBride WH, Haustermans KM. Insulin-like growth factor-type 1 receptor inhibitor NVP-AEW541 enhances radiosensitivity of PTEN wild-type but not PTEN-deficient human prostate cancer cells. Int J Radiat Oncol Biol Phys. 2011 Sep 1;81(1):239-47. PubMed PMID: 21816290.

2: Attias-Geva Z, Bentov I, Fishman A, Werner H, Bruchim I. Insulin-like growth factor-I receptor inhibition by specific tyrosine kinase inhibitor NVP-AEW541 in endometrioid and serous papillary endometrial cancer cell lines. Gynecol Oncol. 2011 May 1;121(2):383-9. Epub 2011 Feb 3. PubMed PMID: 21295335.

3: Premkumar DR, Jane EP, Pollack IF. Co-administration of NVP-AEW541 and dasatinib induces mitochondrial-mediated apoptosis through Bax activation in malignant human glioma cell lines. Int J Oncol. 2010 Sep;37(3):633-43. PubMed PMID: 20664932.

4: Gariboldi MB, Ravizza R, Monti E. The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells. Biochem Pharmacol. 2010 Aug 15;80(4):455-62. Epub 2010 May 19. PubMed PMID: 20488164.

5: Hägerstrand D, Lindh MB, Peña C, Garcia-Echeverria C, Nistér M, Hofmann F, Ostman A. PI3K/PTEN/Akt pathway status affects the sensitivity of high-grade glioma cell cultures to the insulin-like growth factor-1 receptor inhibitor NVP-AEW541. Neuro Oncol. 2010 Sep;12(9):967-75. Epub 2010 Apr 8. PubMed PMID: 20378689; PubMed Central PMCID: PMC2940698.

6: Wolf S, Lorenz J, Mössner J, Wiedmann M. Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance. World J Gastroenterol. 2010 Jan 14;16(2):156-66. PubMed PMID: 20066734; PubMed Central PMCID: PMC2806553.

7: Mukohara T, Shimada H, Ogasawara N, Wanikawa R, Shimomura M, Nakatsura T, Ishii G, Park JO, Jänne PA, Saijo N, Minami H. Sensitivity of breast cancer cell lines to the novel insulin-like growth factor-1 receptor (IGF-1R) inhibitor NVP-AEW541 is dependent on the level of IRS-1 expression. Cancer Lett. 2009 Sep 8;282(1):14-24. Epub 2009 Apr 3. PubMed PMID: 19345478.

8: Baumann P, Hagemeier H, Mandl-Weber S, Franke D, Schmidmaier R. Myeloma cell growth inhibition is augmented by synchronous inhibition of the insulin-like growth factor-1 receptor by NVP-AEW541 and inhibition of mammalian target of rapamycin by Rad001. Anticancer Drugs. 2009 Apr;20(4):259-66. PubMed PMID: 19240643.

9: Cunningham MP, Thomas H, Marks C, Green M, Fan Z, Modjtahedi H. Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol. 2008 Nov;33(5):1107-13. PubMed PMID: 18949375.

10: Moser C, Schachtschneider P, Lang SA, Gaumann A, Mori A, Zimmermann J, Schlitt HJ, Geissler EK, Stoeltzing O. Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. Eur J Cancer. 2008 Jul;44(11):1577-86. Epub 2008 Apr 27. PubMed PMID: 18445520.

11: Maiso P, Ocio EM, Garayoa M, Montero JC, Hofmann F, García-Echeverría C, Zimmermann J, Pandiella A, San Miguel JF. The insulin-like growth factor-I receptor inhibitor NVP-AEW541 provokes cell cycle arrest and apoptosis in multiple myeloma cells. Br J Haematol. 2008 May;141(4):470-82. Epub 2008 Mar 12. PubMed PMID: 18341634.

12: Tazzari PL, Tabellini G, Bortul R, Papa V, Evangelisti C, Grafone T, Martinelli G, McCubrey JA, Martelli AM. The insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 induces apoptosis in acute myeloid leukemia cells exhibiting autocrine insulin-like growth factor-I secretion. Leukemia. 2007 May;21(5):886-96. Epub 2007 Mar 15. PubMed PMID: 17361225.

13: Tanno B, Mancini C, Vitali R, Mancuso M, McDowell HP, Dominici C, Raschellà G. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006 Nov 15;12(22):6772-80. PubMed PMID: 17121898.

14: Scotlandi K, Manara MC, Nicoletti G, Lollini PL, Lukas S, Benini S, Croci S, Perdichizzi S, Zambelli D, Serra M, García-Echeverría C, Hofmann F, Picci P. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res. 2005 May 1;65(9):3868-76. PubMed PMID: 15867386.

15: García-Echeverría C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, Evans DB, Fabbro D, Furet P, Porta DG, Liebetanz J, Martiny-Baron G, Ruetz S, Hofmann F. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004 Mar;5(3):231-9. PubMed PMID: 15050915.