AEE-788

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

Description:AEE-788 is an orally bioavailable multiple-receptor tyrosine kinase inhibitor. AEE788 inhibits phosphorylation of the tyrosine kinases of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor receptor 2 (VEGF2), resulting in receptor inhibition, the inhibition of cellular proliferation, and induction of tumor cell and tumor-associated endothelial cell apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Price and Availability

AEE-788, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200100Name: AEE-788CAS#: 497839-62-0Chemical Formula: C27H32N6Exact Mass: 440.26885Molecular Weight: 440.58Elemental Analysis: C, 73.60; H, 7.32; N, 19.07

Synonym:AEE788; AEE 788; AEE-788.

IUPAC/Chemical Name:(R)-6-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine.

InChi Key:OONFNUWBHFSNBT-HXUWFJFHSA-N

InChi Code:InChI=1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1

SMILES Code:C[C@@H](NC1=C2C(NC(C3=CC=C(CN4CCN(CC)CC4)C=C3)=C2)=NC=N1)C5=CC=CC=C5

Technical Data

Additional Information

AEE788 is a multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1.  In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of intermittent treatment schedules. It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters.  (http://en.wikipedia.org/wiki/AEE788)AEE788 is a multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1.  In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of intermittent treatment schedules. It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters.  (http://en.wikipedia.org/wiki/AEE788)  

References

1: Behera R, Thomas SM, Mensa-Wilmot K. New chemical scaffolds for human africantrypanosomiasis lead discovery from a screen of tyrosine kinase inhibitor drugs.Antimicrob Agents Chemother. 2014;58(4):2202-10. doi: 10.1128/AAC.01691-13. Epub2014 Jan 27. PubMed PMID: 24468788; PubMed Central PMCID: PMC4023774.

2: Ren J, Bollu LR, Su F, Gao G, Xu L, Huang WC, Hung MC, Weihua Z. EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors. Prostate. 2013 Sep;73(13):1453-61. doi: 10.1002/pros.22692. Epub 2013 Jun 14. PubMed PMID:23765757.

3: Katiyar S, Kufareva I, Behera R, Thomas SM, Ogata Y, Pollastri M, Abagyan R, Mensa-Wilmot K. Lapatinib-binding protein kinases in the African trypanosome: identification of cellular targets for kinase-directed chemical scaffolds. PLoS One. 2013;8(2):e56150. doi: 10.1371/journal.pone.0056150. Epub 2013 Feb 20. Erratum in: PLoS One. 2014;9(3):e92488. PubMed PMID: 23437089; PubMed Central PMCID: PMC3577790.

4: Issa A, Gill JW, Heideman MR, Sahin O, Wiemann S, Dey JH, Hynes NE. Combinatorial targeting of FGF and ErbB receptors blocks growth and metastatic spread of breast cancer models. Breast Cancer Res. 2013 Jan 23;15(1):R8. doi: 10.1186/bcr3379. PubMed PMID: 23343422; PubMed Central PMCID: PMC3672810.

5: Baselga J, Mita AC, Schöffski P, Dumez H, Rojo F, Tabernero J, DiLea C, Mietlowski W, Low C, Huang J, Dugan M, Parker K, Walk E, van Oosterom A, Martinelli E, Takimoto CH. Using pharmacokinetic and pharmacodynamic data in early decision making regarding drug development: a phase I clinical trial evaluating tyrosine kinase inhibitor, AEE788. Clin Cancer Res. 2012 Nov 15;18(22):6364-72. doi: 10.1158/1078-0432.CCR-12-1499. Epub 2012 Sep 26. PubMed PMID: 23014528.

6: Venkatesan P, Bhutia SK, Singh AK, Das SK, Dash R, Chaudhury K, Sarkar D, Fisher PB, Mandal M. AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells. Life Sci. 2012 Oct 22;91(15-16):789-99. doi: 10.1016/j.lfs.2012.08.024. Epub 2012 Aug 24. PubMed PMID: 22922496.

7: Reardon DA, Conrad CA, Cloughesy T, Prados MD, Friedman HS, Aldape KD, Mischel P, Xia J, DiLea C, Huang J, Mietlowski W, Dugan M, Chen W, Yung WK. Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients. Cancer Chemother Pharmacol. 2012 Jun;69(6):1507-18. doi: 10.1007/s00280-012-1854-6. Epub 2012 Mar 7. PubMed PMID: 22392572; PubMed Central PMCID: PMC4351868.

8: Servidei T, Meco D, Trivieri N, Patriarca V, Vellone VG, Zannoni GF, Lamorte G, Pallini R, Riccardi R. Effects of epidermal growth factor receptor blockade on ependymoma stem cells in vitro and in orthotopic mouse models. Int J Cancer. 2012 Sep 1;131(5):E791-803. doi: 10.1002/ijc.27377. Epub 2012 Jan 11. PubMed PMID: 22120695.

9: Reardon DA, Cloughesy T, Rich J, Alfred Yung WK, Yung L, DiLea C, Huang J, Dugan M, Mietlowski W, Maes A, Conrad C. Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma. CancerChemother Pharmacol. 2012 Jan;69(1):281-7. doi: 10.1007/s00280-011-1754-1. Epub 2011 Oct 9. PubMed PMID: 21984222.

10: Wedel S, Hudak L, Seibel JM, Makarević J, Juengel E, Tsaur I, Waaga-Gasser A, Haferkamp A, Blaheta RA. Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis. BMC Cancer. 2011 Aug 25;11:375. doi: 10.1186/1471-2407-11-375. PubMed PMID: 21867506; PubMed Central PMCID: PMC3170298.