Computational counterselection identifies nonspecific therapeutic biologic candidates.

Effective biologics require high specificity and limited off-target binding, but these properties are not guaranteed by current affinity-selection-based discovery methods. Molecular counterselection against off targets is a technique for identifying nonspecific sequences but is experimentally costly and can fail to eliminate a large fraction of nonspecific sequences. Here, we introduce computational counterselection, a framework for removing nonspecific sequences from pools of candidate biologics using machine learning models.

Diselaginellin B, an Unusual Dimeric Molecule from Selaginella pulvinata, Inhibited Metastasis and Induced Apoptosis of SMMC-7721 Human Hepatocellular Carcinoma Cells.

Two new unusual dimeric selaginellins, diselaginellins A and B (1 and 2), along with two known derivatives, selaginellin (3) and selaginellin B (4), were isolated from Selaginella pulvinata. Their structures were elucidated by extensive NMR and high-resolution ESIMS data analysis. Compound 2 displayed apoptosis-inducing and antimetastatic activities against the human hepatocellular carcinoma cell line SMMC-7721.

Transfection of insect cell in suspension for efficient baculovirus generation.

Baculovirus (BV) mediated insect cell expression system utilizes transfection as a first step to introduce recombinant baculovirus DNA into insect cells. Many labs are still relying on the conventional liposome based transfection method in adherent culture. Here we describe a more efficient method that can replace the existing method.

Use of solubilizers in preclinical formulations: Effect of Cremophor EL on the pharmacokinetic properties on early discovery compounds.

The aim of the present study was to determine whether Cremophor EL is a suitable surfactant that can be routinely applied to pharmacokinetic (PK) studies in early drug discovery without influencing the intrinsic PK characteristics of the new chemical entities (NCEs). Cremophor EL, a polyoxyl 35 castor oil, has been used as a solubilization aid for water-insoluble compounds in pre-clinical drug discovery. The effect of Cremophor EL on the PK properties of NCEs was examined in seven structurally diverse discovery compounds after intravenous administration.

Human non-pigmented ciliary epithelium bradykinin B2-receptors: receptor localization, pharmacological characterization of intracellular Ca(2+) mobilization, and prostaglandin secretion.

Purpose: To characterize the bradykinin (BK) receptor system in human non-pigmented ciliary epithelium (NPCE) using immunohistochemistry and functional cell-based techniques.

Methods: B2-receptor protein expression was studied in sections of human donor eyes and in Cynomolgus monkey eyes using immunohistochemical methods. The pharmacological characteristics of intracellular Ca(2+) ([Ca(2+)]i) mobilization in response to BK and related peptides, and blockade by two antagonists, was studied in primary human (p-h-NPCE) and in immortalized human NPCE (imh-NPCE) cells.