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.^[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.^[2][3]

AEE788

Identifiers
IUPAC name 6-[4-[(4-Ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
CAS Number	497839-62-0 N
PubChem CID	10297043
IUPHAR/BPS	7643
ChemSpider	8472511 Y
UNII	F9JLR95I3I
ChEBI	CHEBI:40629
ChEMBL	ChEMBL587723 Y
CompTox Dashboard (EPA)	DTXSID90964400
Chemical and physical data
Formula	C27H32N6
Molar mass	440.595 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
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 Y Key:OONFNUWBHFSNBT-HXUWFJFHSA-N Y
NY (what is this?)  (verify)

The IC50 value of AEE788 against of different kinases

Kinase	IC50(nM)
EGFR ICD	2
ErbB2(HER-2)	6
ErbB4 (HER-4)	160
KDR	77
Tek	2100
IGF1-R	>10000
Ins-R	>10000
PDGFR-beta	320
c-Met	2900
c-Abl	52
c-Src	61
c-Kit	790
RET	740
c-Fms	60
Flt-1	59
Flt-3	730
Flt-4	330
Cdk1/Cyc.B	8000
PKC-alpha	>10000
c-Raf-1	2800
PKA	>10000

The data of antiproliferative activity of AEE788

Cell line	IC50(nM)
NCI-H596	78
MK	56
BT-474	49
SK-BR-3	381
32D/EGFR	300
32D/EGFRvIII	10
MCF-7	2500
MCF-7/EGFRvIII	<5000
T24	4526