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In vivo Anti-Cancer Activity of a Liposomal Nanoparticle Construct of Multifunctional Tyrosine Kinase Inhibitor 4-(4'-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline
Ilker Dibirdik, Seang Yiv, Sanjive Qazi and Fatih M. Uckun
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.