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Drug-Target Interaction

Drug

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PubChem ID:4713
Structure:
Synonyms:
"2′-amino-3′-methoxyflavone"
167869-21-8
2′-Amino-3′-methoxyflavone
2'-AMINO-3'-METHOXYFLAVONE
2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one
2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
2-(2-Amino-3-methoxyphenyl)-chromen-4-one
2-(2-amino-3-methoxyphenyl)chromen-4-one
4H-1-Benzopyran-4-one, 2-(2-amino-3-methoxyphenyl)-
4H-1-Benzopyran-4-one, 2-(2-amino-3-methoxyphenyl)- & Z-100
AC1L1ISD
AC1Q6AK0
AIDS-220091
AIDS220091
AR-1C6511
BCBcMAP01_000049
Bio1_000475
Bio1_000964
Bio1_001453
Bio2_000338
Bio2_000818
BiomolKI2_000011
BiomolKI_000001
BIP0711
BMK1-B1
BRD-K62810658-001-05-6
BSPBio_000996
C093973
CCG-100605
CHEBI:150222
CHEMBL35482
EC-000.2425
EU-0101028
HMS1362B17
HMS1792B17
HMS1990B17
HMS3229M08
HMS3263M17
IDI1_002093
IN1172
KBio2_000336
KBio2_002904
KBio2_005472
KBio3_000671
KBio3_000672
KBioGR_000336
KBioSS_000336
Lopac-P-215
Lopac0_001028
LS-182409
MolPort-000-005-902
NCGC00015790-01
NCGC00015790-02
NCGC00015790-03
NCGC00015790-04
NCGC00015790-05
NCGC00015790-06
NCGC00015790-07
NCGC00015790-08
NCGC00025045-01
NCGC00025045-02
NCGC00025045-03
NCGC00025045-04
NCGC00025045-05
NCGC00179347-01
nchembio.282-comp4
NCI60_028554
NSC679828
P-215
P215_SIGMA
PD 098059
PD 98,059
PD 98059
PD 98059 & Z-100
PD 98059, PD98059
PD-098059
PD-98059
PD098059
PD09859
PD98059
PD98059-Supplied by Selleck Chemicals
S1177_Selleck
SMP2_000052
Tocris-1213
ZINC01420826

Target

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Uniprot ID:PK3C3_HUMAN
Synonyms:
Phosphatidylinositol 3-kinase catalytic subunit type 3
Phosphatidylinositol 3-kinase p100 subunit
Phosphoinositide-3-kinase class 3
PI3-kinase type 3
PI3K type 3
PtdIns-3-kinase type 3
EC-Numbers:2.7.1.137
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

16419029
The MEK/MAPK pathway is involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib.. Nicola Normanno; Antonella De Luca; Monica R Maiello; Manuela Campiglio; Maria Napolitano; Mario Mancino; Adele Carotenuto; Giuseppe Viglietto; Sylvie Menard (2006) Journal of cellular physiology display abstract
We investigated the role of the MEK/MAPK pathway in the sensitivity/resistance of breast carcinoma cells to the EGFR tyrosine kinase inhibitor gefitinib (IRESSA). We assessed the effects of gefitinib on the growth of three breast cancer cell lines that showed high (SK-Br-3; IC50 4 microM), intermediate (MDA-MB-361; IC50 5.3 microM), and low (MDA-MB-468; IC50 6.8 microM) sensitivity to the drug. Although treatment with gefitinib inhibited EGFR activation in the three cell lines in a similar fashion, significant reduction of both p42/p44-MAPK and AKT phosphorylation was observed in SK-Br-3 and MDA-MB-361, but not in MDA-MB-468 cells. The growth of MDA-MB-468 cells was significantly inhibited by treatment with either the PI3K-inhibitor LY294002 or the MEK-inhibitor PD98059. In agreement with these findings, treatment of MDA-MB-468 cells with a combination of PD98059 and gefitinib produced a synergistic anti-tumor effect, whereas this combination was only additive in SK-Br-3 and MDA-MB-361 cells. The combination of gefitinib and PD98059 also produced a significant increase in the levels of apoptosis in MDA-MB-468 cells as compared with treatment with a single agent. This phenomenon was associated with a profound decrease in MAPK activation, reduction of BAD (ser112) phosphorylation and a paradoxical increase in the levels of AKT activation. Finally, overexpression of a constitutively activated form of p42-MAPK in MCF-10A non-transformed human mammary epithelial cells resulted in a two- to three-fold increase in the IC50 to gefitinib. Taken together, these data strongly support the role of the MEK/MAPK pathway in the resistance to gefitinib, and provide the rationale for novel therapeutic approaches based on combinations of signal transduction inhibitors.