NAPHTHOL AS-E PHOSPHATE

• CAT Number: R068764
• CAS Number: 18228-17-6
• Molecular Formula: C17H13ClNO5P
• Molecular Weight: 377.717
• Purity: ≥95%
• Synonyms: KG-501, N-(4-Chlorophenyl)-3-(phosphonooxy)naphthalene-2-carboxamide, NASEP
• Storage: Desiccate at RT
• IUPAC Name: [3-[(4-chlorophenyl)carbamoyl]naphthalen-2-yl] dihydrogen phosphate
• InChI: InChI=1S/C17H13ClNO5P/c18-13-5-7-14(8-6-13)19-17(20)15-9-11-3-1-2-4-12(11)10-16(15)24-25(21,22)23/h1-10H,(H,19,20)(H2,21,22,23)
• InChIKey: RQAQWBFHPMSXKR-UHFFFAOYSA-N
• SMILES: C1=CC=C2C=C(C(=CC2=C1)C(=O)NC3=CC=C(C=C3)Cl)OP(=O)(O)O

NAPHTHOL AS-E PHOSPHATE(cas# 18228-17-6) is a histochemical substrate for alkaline phosphatases.  It blocks cAMP-induction of CREB (cAMP Response Element Binding Protein)-dependent target gene transcription (Ki 10 microM)) through interference in the binding between the KID domain of CREB and KIX domain of CBP (CREB Binding Protein), classic activator-coactivator interaction. 

Reference

1. Mol Cancer Ther. 2015 Jun;14(6):1276-85. doi: 10.1158/1535-7163.MCT-14-0662. Epub
2015 Mar 4.

Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by
Blocking the Interaction with the KIX Domain of the Coactivator p300.

Uttarkar S(1), Dukare S(1), Bopp B(2), Goblirsch M(2), Jose J(2), Klempnauer
KH(3).

Author information:
(1)Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster,
Münster, Germany. Graduate School of Chemistry (GSC-MS),
Westfälische-Wilhelms-Universität Münster, Münster, Germany.
(2)Institute for Pharmaceutical and Medicinal Chemistry,
Westfälische-Wilhelms-Universität Münster, Münster, Germany.
(3)Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster,
Münster, Germany. .

Comment in
Mol Cancer Ther. 2015 Jun;14(6):1273-5.

The transcription factor c-Myb is highly expressed in hematopoietic progenitor
cells and controls the transcription of genes important for lineage
determination, cell proliferation, and differentiation. Deregulation of c-Myb has
been implicated in the development of leukemia and certain other types of human
cancer. c-Myb activity is highly dependent on the interaction of the c-Myb with
the KIX domain of the coactivator p300, making the disruption of this interaction
a reasonable strategy for the development of Myb inhibitors. Here, we have used
bacterial Autodisplay to develop an in vitro binding assay that mimics the
interaction of Myb and the KIX domain of p300. We have used this binding assay to
investigate the potential of Naphthol AS-E phosphate, a compound known to bind to
the KIX domain, to disrupt the interaction between Myb and p300. Our data show
that Naphthol AS-E phosphate interferes with the Myb-KIX interaction in vitro and
inhibits Myb activity in vivo. By using several human leukemia cell lines, we
demonstrate that Naphthol AS-E phosphate suppresses the expression of Myb target
genes and induces myeloid differentiation and apoptosis. Our work identifies
Naphthol AS-E phosphate as the first low molecular weight compound that inhibits
Myb activity by disrupting its interaction with p300, and suggests that
inhibition of the Myb-KIX interaction might be a useful strategy for the
treatment of leukemia and other tumors caused by deregulated c-Myb.