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Drug-Target Interaction

Drug

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PubChem ID:389710
Structure:
Synonyms:
165179-35-1
4H-1-Benzopyran-4-one,
4H-1-Benzopyran-4-one, 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-
5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4h-chromen-4-one
5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methylchromen-4-one
AC1L8YIV
AC1Q53D6
AMINOFLAVONE
AR-1G7043
CCG-35825
CHEMBL62006
NCI60_031035
NCIMech_000858
NSC686288

Target

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Uniprot ID:CP1A1_HUMAN
Synonyms:
CYPIA1
Cytochrome P450 1A1
P450 form 6
P450-C
P450-P1
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

18059023
Aminoflavone induces oxidative DNA damage and reactive oxidative species-mediated apoptosis in breast cancer cells.. Lancelot McLean; Ubaldo Soto; Keli Agama; Jawad Francis; Randi Jimenez; Yves Pommier; Lawrence Sowers; Eileen Brantley (2008) International journal of cancer. Journal international du cancer display abstract
Aminoflavone (5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methylchromen-4-one; AF; NSC 686288), a novel anticancer candidate agent, is undergoing clinical evaluation. AF induces DNA-protein cross-links (DPCs), Gamma-H2AX phosphorylation, aryl hydrocarbon receptor (AhR) signaling, apoptosis and its own metabolism via cytochrome P4501A1 and 1A2 (CYP1A1/1A2) activation in sensitive estrogen receptor positive (ER+) MCF7 breast cancer cells. Estrogen receptor negative (ER-) breast cancer is typically more aggressive with a poorer prognosis. In this investigation, we evaluated the ability of AF to induce reactive oxygen species (ROS) formation, oxidative DNA damage and apoptosis in ER- MDA-MB-468 breast cancer cells. The antioxidant, N-acetyl-L-cysteine (NAC), attenuated the cytotoxic effects of AF in MDA-MB-468 cells; an effect is also observed in ER+ T47D breast cancer cells. Nonmalignant MCF10A breast epithelial cells were resistant to the cytotoxic effects of AF. AF increased intracellular ROS, an effect blocked by NAC and the CYP1A1/1A2 inhibitor, alpha-Naphthoflavone (alpha-NF). AF induced oxidative DNA damage as evidenced by increased 8-oxo-7,8-dihydroguanine (8-oxodG) levels and DPC formation in these cells. AF caused S-phase arrest corresponding to an increase in p21((waf1/cip1)) protein expression. AF induced caspase 3, 8 and 9 activation, caspase-dependent apoptotic body formation and poly [ADP-ribose] polymerase (PARP) cleavage. Pretreatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp(OMe)-fluoromethylketone inhibited apoptosis and partially inhibited ROS formation and oxidative DNA damage. Pretreatment with NAC attenuated AF-induced apoptotic body formation and caspase 3 activation. These studies suggest AF inhibits the growth of breast cancer cells in part, by inducing ROS production, oxidative DNA damage and apoptosis and has the potential to treat hormone-independent breast cancer.