CHEBI:40629 - AEE788

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ChEBI Name AEE788
ChEBI ID CHEBI:40629
Definition A 6-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine which adopts an R-configuration. It is a potent inhibitor of human EGFR, VEGFR and HER2 receptor tyrosine kinases and exhibits anticancer and antiangiogenic activity.
Stars This entity has been manually annotated by the ChEBI Team.
Supplier Information eMolecules:31591966, Selleckchem:AEE788, ZINC000022453679
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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.
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Formula C27H32N6
Net Charge 0
Average Mass 440.595
Monoisotopic Mass 440.26885
InChI 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
InChIKey OONFNUWBHFSNBT-HXUWFJFHSA-N
SMILES CCN1CCN(CC2=CC=C(C=C2)C2=CC3=C(N[C@H](C)C4=CC=CC=C4)N=CN=C3N2)CC1
Roles Classification
Chemical Role(s): Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Biological Role(s): epidermal growth factor receptor antagonist
An antagonist at the epidermal growth factor receptor.
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
An EC 2.7.10.* (protein-tyrosine kinase) inhibitor that interferes with the action of receptor protein-tyrosine kinase (EC 2.7.10.1).
trypanocidal drug
A drug used to treat or prevent infections caused by protozoal organisms belonging to the suborder Trypanosomatida.
apoptosis inducer
Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
Application(s): antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
angiogenesis inhibitor
An agent and endogenous substances that antagonize or inhibit the development of new blood vessels.
trypanocidal drug
A drug used to treat or prevent infections caused by protozoal organisms belonging to the suborder Trypanosomatida.
View more via ChEBI Ontology
ChEBI Ontology
Outgoing AEE788 (CHEBI:40629) has role angiogenesis inhibitor (CHEBI:48422)
AEE788 (CHEBI:40629) has role antineoplastic agent (CHEBI:35610)
AEE788 (CHEBI:40629) has role apoptosis inducer (CHEBI:68495)
AEE788 (CHEBI:40629) has role EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor (CHEBI:62434)
AEE788 (CHEBI:40629) has role epidermal growth factor receptor antagonist (CHEBI:74440)
AEE788 (CHEBI:40629) has role trypanocidal drug (CHEBI:36335)
AEE788 (CHEBI:40629) is a 6-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (CHEBI:170005)
IUPAC Name
6-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
Synonyms Sources
6-{4-[(4-ethyl-1-piperazinyl)methyl]phenyl}-N-[(1R)-1-phenylethyl]-1H-pyrrolo[2,3-d]pyrimidin-4-amine ChEBI
[6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine ChEBI
AEE 788 ChemIDplus
AEE-788 ChemIDplus
NVP-AEE-788 DrugBank
NVP-AEE788 ChemIDplus
Manual Xrefs Databases
8472511 ChemSpider
AEE PDBeChem
AEE788 Wikipedia
DB12558 DrugBank
LSM-45507 LINCS
View more database links
Registry Number Type Source
497839-62-0 CAS Registry Number ChemIDplus
Citations
He J, McLaughlin RP, van der Noord V, Foekens JA, Martens JWM, van Westen G, Zhang Y, van de Water B (2019)
Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer.
Breast cancer research and treatment 178, 263-274 [PubMed:31388935]
[show Abstract]
Kim M, Laramy JK, Mohammad AS, Talele S, Fisher J, Sarkaria JN, Elmquist WF (2019)
Brain Distribution of a Panel of Epidermal Growth Factor Receptor Inhibitors Using Cassette Dosing in Wild-Type and Abcb1/Abcg2-Deficient Mice.
Drug metabolism and disposition: the biological fate of chemicals 47, 393-404 [PubMed:30705084]
[show Abstract]
Sullenberger C, Piqué D, Ogata Y, Mensa-Wilmot K (2017)
AEE788 Inhibits Basal Body Assembly and Blocks DNA Replication in the African Trypanosome.
Molecular pharmacology 91, 482-498 [PubMed:28246189]
[show Abstract]
Valverde A, Peñarando J, Cañas A, López-Sánchez LM, Conde F, Hernández V, Peralbo E, López-Pedrera C, de la Haba-Rodríguez J, Aranda E, Rodríguez-Ariza A (2015)
Simultaneous inhibition of EGFR/VEGFR and cyclooxygenase-2 targets stemness-related pathways in colorectal cancer cells.
PloS one 10, e0131363 [PubMed:26107817]
[show Abstract]
Behera R, Thomas SM, Mensa-Wilmot K (2014)
New chemical scaffolds for human african trypanosomiasis lead discovery from a screen of tyrosine kinase inhibitor drugs.
Antimicrobial agents and chemotherapy 58, 2202-2210 [PubMed:24468788]
[show Abstract]
Reardon DA, Cloughesy T, Rich J, Alfred Yung WK, Yung L, DiLea C, Huang J, Dugan M, Mietlowski W, Maes A, Conrad C (2012)
Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma.
Cancer chemotherapy and pharmacology 69, 281-287 [PubMed:21984222]
[show Abstract]
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 (2012)
Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients.
Cancer chemotherapy and pharmacology 69, 1507-1518 [PubMed:22392572]
[show Abstract]
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 (2012)
Using pharmacokinetic and pharmacodynamic data in early decision making regarding drug development: a phase I clinical trial evaluating tyrosine kinase inhibitor, AEE788.
Clinical cancer research : an official journal of the American Association for Cancer Research 18, 6364-6372 [PubMed:23014528]
[show Abstract]
Venkatesan P, Bhutia SK, Singh AK, Das SK, Dash R, Chaudhury K, Sarkar D, Fisher PB, Mandal M (2012)
AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells.
Life sciences 91, 789-799 [PubMed:22922496]
[show Abstract]
Deng M, Huang H, Jin H, Dirsch O, Dahmen U (2011)
The anti-proliferative side effects of AEE788, a tyrosine kinase inhibitor blocking both EGF- and VEGF-receptor, are liver-size-dependent after partial hepatectomy in rats.
Investigational new drugs 29, 593-606 [PubMed:20148349]
[show Abstract]
Wedel S, Hudak L, Seibel JM, Juengel E, Oppermann E, Haferkamp A, Blaheta RA (2011)
Critical analysis of simultaneous blockage of histone deacetylase and multiple receptor tyrosine kinase in the treatment of prostate cancer.
The Prostate 71, 722-735 [PubMed:20954195]
[show Abstract]
Juengel E, Engler J, Mickuckyte A, Jones J, Hudak L, Jonas D, Blaheta RA (2010)
Effects of combined valproic acid and the epidermal growth factor/vascular endothelial growth factor receptor tyrosine kinase inhibitor AEE788 on renal cell carcinoma cell lines in vitro.
BJU international 105, 549-557 [PubMed:19594733]
[show Abstract]
Evans AH, Pancholi S, Farmer I, Thornhill A, Evans DB, Johnston SR, Dowsett M, Martin LA (2010)
EGFR/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2/ER-positive breast cancer cells but functions synergistically with endocrine therapy.
British journal of cancer 102, 1235-1243 [PubMed:20386540]
[show Abstract]
Deng M, Huang H, Dirsch O, Dahmen U (2010)
Effect and risk of AEE788, a dual tyrosine kinase inhibitor, on regeneration in a rat liver resection model.
European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 44, 82-95 [PubMed:20090347]
[show Abstract]
Barbarroja N, Torres LA, Rodriguez-Ariza A, Valverde-Estepa A, Lopez-Sanchez LM, Ruiz-Limon P, Perez-Sanchez C, Carretero RM, Velasco F, López-Pedrera C (2010)
AEE788 is a vascular endothelial growth factor receptor tyrosine kinase inhibitor with antiproliferative and proapoptotic effects in acute myeloid leukemia.
Experimental hematology 38, 641-652 [PubMed:20380868]
[show Abstract]
Berezowska S, Diermeier-Daucher S, Brockhoff G, Busch R, Duyster J, Grosu AL, Schlegel J (2010)
Effect of additional inhibition of human epidermal growth factor receptor 2 with the bispecific tyrosine kinase inhibitor AEE788 on the resistance to specific EGFR inhibition in glioma cells.
International journal of molecular medicine 26, 713-721 [PubMed:20878094]
[show Abstract]
Venkatesan P, Das S, Krishnan MM, Chakraborty C, Chaudhury K, Chaudhury K, Mandal M (2010)
Effect of AEE788 and/or Celecoxib on colon cancer cell morphology using advanced microscopic techniques.
Micron (Oxford, England : 1993) 41, 247-256 [PubMed:19945288]
[show Abstract]
Nakachi I, Naoki K, Soejima K, Kawada I, Watanabe H, Yasuda H, Nakayama S, Yoda S, Satomi R, Ikemura S, Terai H, Sato T, Ishizaka A (2010)
The combination of multiple receptor tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor overcomes erlotinib resistance in lung cancer cell lines through c-Met inhibition.
Molecular cancer research : MCR 8, 1142-1151 [PubMed:20647329]
[show Abstract]
Meco D, Servidei T, Zannoni GF, Martinelli E, Prisco MG, de Waure C, Riccardi R (2010)
Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma.
Translational oncology 3, 326-335 [PubMed:20885895]
[show Abstract]
Juengel E, Engler J, Natsheh I, Jones J, Mickuckyte A, Hudak L, Jonas D, Blaheta RA (2009)
Combining the receptor tyrosine kinase inhibitor AEE788 and the mammalian target of rapamycin (mTOR) inhibitor RAD001 strongly inhibits adhesion and growth of renal cell carcinoma cells.
BMC cancer 9, 161 [PubMed:19473483]
[show Abstract]
Wedel SA, Mickuckyte A, Juengel E, Jones J, Hudak L, Jonas D, Blaheta RA (2008)
[Preclinical studies on the influence of the tyrosine kinase inhibitor AEE788 on malignant properties of renal cell carcinoma cells].
Der Urologe. Ausg. A 47, 1175-1181 [PubMed:18688594]
[show Abstract]
Okamoto K, Neureiter D, Alinger B, Meissnitzer M, Sass G, Schmitz V, Di Fazio P, Wissniowski T, Gahr S, Hohenstein B, Kaufmann B, Schlösser A, Haus U, Hahn EG, Herold C, Ocker M (2008)
The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice.
International journal of oncology 33, 733-742 [PubMed:18813786]
[show Abstract]
Huamani J, Willey C, Thotala D, Niermann KJ, Reyzer M, Leavitt L, Jones C, Fleishcher A, Caprioli R, Hallahan DE, Kim DW (2008)
Differential efficacy of combined therapy with radiation and AEE788 in high and low EGFR-expressing androgen-independent prostate tumor models.
International journal of radiation oncology, biology, physics 71, 237-246 [PubMed:18337021]
[show Abstract]
Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ (2008)
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP.
Proceedings of the National Academy of Sciences of the United States of America 105, 2070-2075 [PubMed:18227510]
[show Abstract]
Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ (2007)
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.
Cancer cell 11, 217-227 [PubMed:17349580]
[show Abstract]
Yu C, Friday BB, Lai JP, McCollum A, Atadja P, Roberts LR, Adjei AA (2007)
Abrogation of MAPK and Akt signaling by AEE788 synergistically potentiates histone deacetylase inhibitor-induced apoptosis through reactive oxygen species generation.
Clinical cancer research : an official journal of the American Association for Cancer Research 13, 1140-1148 [PubMed:17317822]
[show Abstract]
Oehler-Jänne C, Jochum W, Riesterer O, Broggini-Tenzer A, Caravatti G, Vuong V, Pruschy M (2007)
Hypoxia modulation and radiosensitization by the novel dual EGFR and VEGFR inhibitor AEE788 in spontaneous and related allograft tumor models.
Molecular cancer therapeutics 6, 2496-2504 [PubMed:17876047]
[show Abstract]
Wiedmann M, Feisthammel J, Blüthner T, Tannapfel A, Kamenz T, Kluge A, Mössner J, Caca K (2006)
Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.
Anti-cancer drugs 17, 783-795 [PubMed:16926628]
[show Abstract]
Younes MN, Yazici YD, Kim S, Jasser SA, El-Naggar AK, Myers JN (2006)
Dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition with NVP-AEE788 for the treatment of aggressive follicular thyroid cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research 12, 3425-3434 [PubMed:16740767]
[show Abstract]
Park YW, Younes MN, Jasser SA, Yigitbasi OG, Zhou G, Bucana CD, Bekele BN, Myers JN (2005)
AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice.
Clinical cancer research : an official journal of the American Association for Cancer Research 11, 1963-1973 [PubMed:15756022]
[show Abstract]
Kim S, Schiff BA, Yigitbasi OG, Doan D, Jasser SA, Bekele BN, Mandal M, Myers JN (2005)
Targeted molecular therapy of anaplastic thyroid carcinoma with AEE788.
Molecular cancer therapeutics 4, 632-640 [PubMed:15827337]
[show Abstract]
Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D, Grosios K, Lane HA, McSheehy P, Mestan J, Meyer T, Tang C, Wartmann M, Wood J, Caravatti G (2004)
AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity.
Cancer research 64, 4931-4941 [PubMed:15256466]
[show Abstract]
Yigitbasi OG, Younes MN, Doan D, Jasser SA, Schiff BA, Bucana CD, Bekele BN, Fidler IJ, Myers JN (2004)
Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade.
Cancer research 64, 7977-7984 [PubMed:15520205]
[show Abstract]
Last Modified
23 April 2021