Exploration of macrocyclic peptide binders to the extracellular CRD domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1).

Elevated levels of receptor tyrosine kinase-like orphan receptor 1 (RORl) expression are observed in multiple hematological and solid tumors, but not in most of the healthy adult tissues, identifying ROR1 as an attractive target for tumor-specific therapy. Herein we will describe the discovery of macrocyclic peptides as binders of the extracellular Cysteine-Rich Domain (CRD) of human ROR1 via mRNA in vitro selection technology using the PDPS platform, followed by exploration of sidechain SAR of parent macrocycle peptides, fluorescently labeled analogs, and a Peptide Drug Conjugate (PDC). The parent macrocyclic peptides represented by Compound 1 and Compound 14 displayed nanomolar cell-based binding to ROR1 and relatively good internalization in 786-O and MDA-MB-231 tumor cell lines.

An integrated Qual/Quan strategy for ganglioside lipidomics using high-resolution mass spectrometry and Skyline software.

Rationale: Gangliosides (GS) are attractive targets in biomarker discovery because of their physiological significance in numerous human diseases including certain cancers and developmental and metabolic disorders. The robust strategy described here enables the profiling of numerous GS while obtaining quantitative data of exploratory biomarkers present in human plasma and whole blood.

Method: The GS from human blood, human plasma, and several cell lines were extracted using a mixture of methanol and isopropanol/0.

A Novel, Fully Human Anti-fucosyl-GM1 Antibody Demonstrates Potent and Antitumor Activity in Preclinical Models of Small Cell Lung Cancer.

The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in a large percentage of human small cell lung cancer (SCLC) tumors, but absent in most normal adult tissues, making it a promising target in immuno-oncology. This study was undertaken to evaluate the preclinical efficacy of BMS-986012, a novel, nonfucosylated, fully human IgG1 antibody that binds specifically to FucGM1. The antitumor activity of BMS-986012 was evaluated in assays using SCLC cells and in mouse xenograft and syngeneic tumor models, with and without chemotherapeutic agents and checkpoint inhibitors.

Fucosyl monosialoganglioside: Quantitative analysis of specific potential biomarkers of lung cancer in biological matrices using immunocapture extraction/tandem mass spectrometry.

Rationale: Certain lung cancer patients express elevated Fucosyl Monosialoganglioside (Fuc-GM1) in circulation compared to control groups. Several sensitive methods involving characterization of Fuc-GM1 have been reported. However, a highly specific and sensitive method for quantifying multiple potential Fuc-GM1 biomarkers present in various biological matrices has not been reported to date.

Carrier density modulation in a germanium heterostructure by ferroelectric switching.

The development of non-volatile logic through direct coupling of spontaneous ferroelectric polarization with semiconductor charge carriers is nontrivial, with many issues, including epitaxial ferroelectric growth, demonstration of ferroelectric switching and measurable semiconductor modulation. Here we report a true ferroelectric field effect-carrier density modulation in an underlying Ge(001) substrate by switching of the ferroelectric polarization in epitaxial c-axis-oriented BaTiO3 grown by molecular beam epitaxy. Using the density functional theory, we demonstrate that switching of BaTiO3 polarization results in a large electric potential change in Ge.