Correction to: Metabolic relevance for N-hydroxy L-arginine reduction in estrogen-negative breast cancer cells.

We found a unit error with our LC-MS lower limit of quantitation (LLOQ) measurement in the Amino Acids Journal.

Metabolic relevance for N-hydroxy L-arginine reduction in estrogen-negative breast cancer cells.

We had shown N-hydroxy-L-arginine (NOHA) as a promising blood-based biomarker for estrogen-receptor-negative (ER) breast cancer (BC) that differentiates ER BC based on grade and molecular phenotype. In this in vitro study, we assessed the metabolic relevance for ER BC-specific NOHA modulation and correlated them with NOHA regulatory responses. This study aids future NOHA clinical utility in ER BC diagnosis and therapy management and would prove useful for potential drug discovery and development process.

Assessing N -hydroxy-L-arginine applicability as a novel ethnic specific estrogen-negative breast cancer marker.

In our prior study we identified N -hydroxy-L-arginine (NOHA) as a simple, yet sensitive indicator for estrogen negative (ER) breast cancer early-prognosis, but not estrogen positive (ER), and to offer ethnic selectivity for ER detection. However, the ability of NOHA to assess ER breast tumor based on disease progression, and tumor severity needs further delineation. Also, the overall NOHA storage stability needs to be validated.

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma).

Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors.

Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties.

Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors.

The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy.

Design and structure-activity relationship of heterocyclic analogs of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones as inhibitors of receptor tyrosine kinases.

Herein are described a series of novel heterocyclic analogs of the 4-amino-3-benzimidazol-2-ylhydroquinolin-2-one scaffold. These compounds are potent inhibitors of receptor tyrosine kinases and exhibit favorable pharmacokinetic profiles. The synthesis and SAR of these compounds are described.