alexa In vivo Anti-Cancer Activity of a Liposomal Nanoparticle Construct of Multifunctional Tyrosine Kinase Inhibitor 4-(4'-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline | Abstract
ISSN: 2157-7439

Journal of Nanomedicine & Nanotechnology
Open Access

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Research Article

In vivo Anti-Cancer Activity of a Liposomal Nanoparticle Construct of Multifunctional Tyrosine Kinase Inhibitor 4-(4'-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline

Ilker Dibirdik1,2, Seang Yiv2, Sanjive Qazi3 and Fatih M. Uckun1,2*

1Developmental Therapeutics Program, Institute for Pediatric Clinical Research, Children’s Hospital Los Angeles & Division of Hematology-Oncology, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA

2Molecular Oncology and Drug Discovery Program, Parker Hughes Institute, P.O Box 130366, St. Paul, MN 55113-0004, USA

3Department of Biology, Gustavus Adolphus College, 800 W College Avenue, St. Peter, MN 56082, USA

*Corresponding Author:
Fatih M. Uckun
Developmental Therapeutics Program
Institute for Pediatric Clinical Research
Children’s Hospital Los Angeles Mailstop
#57, Division of Hematology-Oncology
Department of Pediatrics
University of Southern California Keck School of Medicine
4650 Sunset Boulevard, Los Angeles
CA 90027, USA
E-mail: [email protected]

Received Date: August 13, 2010; Accepted Date: August 24, 2010; Published Date: August 24, 2010

Citation: Dibirdik I, Yiv S, Qazi S, Uckun FM (2010) In vivo Anti-Cancer Activity of a Liposomal Nanoparticle Construct of Multifunctional Tyrosine Kinase Inhibitor 4-(4’-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline. J Nanomedic Nanotechnolo 1:101. doi:10.4172/2157-7439.1000101

Copyright: © 2010 Dibirdik I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The quinazoline derivative 4-(4’-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131/JANEX-1; CAS 202475-60-3) is a dual-function inhibitor of Janus kinase 3 (JAK3) and Epidermal Growth Factor (EGF) receptor kinase. A PEGylated liposomal nanoparticle formulation of GMP-grade WHI-P131 exhibited potent in vivo activity against breast cancer cells. Notably, this therapeutic nanoparticle formulation of GMP-grade WHI-P131 was substantially more effective than the standard chemotherapy drugs paclitaxel, gemcitabine, and ge fi tinib against chemotherapy-resistant breast cancer in the MMTV/ Neu transgenic mouse model. These experimental results demonstrate that the nanotechnology- enabled delivery of WHI-P131 shows therapeutic potential against breast cancer.

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