Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models.

Background: Standard approaches to address the performance of predictive models that used common statistical measurements for the entire data set provide an overview of the average performance of the models across the entire predictive space, but give little insight into applicability of the model across the prediction space. Guha and Van Drie recently proposed the use of structure-activity landscape index (SALI) curves via the SALI curve integral (SCI) as a means to map the predictive power of computational models within the predictive space. This approach evaluates model performance by assessing the accuracy of pairwise predictions, comparing compound pairs in a manner similar to that done by medicinal chemists.

Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1.

Initial high throughput screening efforts identified highly potent and selective kappa opioid receptor antagonist 3 (κ IC(50)=77 nM; μ:κ and δ:κ IC(50) ratios>400) which lacked CNS exposure in vivo. Modification of this scaffold resulted in development of a series of 8-azabicyclo[3.2.

Validated assay for the quantification of anastrozole in human plasma by capillary gas chromatography-63Ni electron capture detection.

An assay was developed for the quantification of anastrozole [2,2'-[5-(1H-1,2,4-triazol-1-ymethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile)] in human plasma using liquid-liquid extraction. Anastrozole and an internal standard were chromatographed and detected by gas chromatography with electron capture detection, using a combination temperature-pressure program. The range of the assay is 3 to 100 ng/ml.

Determination of ZD9583, a thromboxane receptor antagonist, in human plasma and urine by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry.

A liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS-MS) method is described for the determination of a thromboxane receptor antagonist (4Z)-6-((2S,4S,5R)-2-(1-(2-cyano-4-methylphenoxy)-1-methylethyl)-4 -(3-pyridyl)-3-dioxan-5-yl)hex-4-enoic acid (ZD9583, I) in human plasma and urine. Proteins in plasma and urine samples are precipitated using acidified acetonitrile. The resulting supernatant is chromatographed on a C8 reversed-phase chromatography column.

Purification and composition of a novel gastrointestinal tumor-associated glycoprotein expressing sialylated lacto-N-fucopentaose II (CA 19-9).

Monoclonal antibody 1116NS 19-9 (Mab 19-9) exhibits selective reactivity with human gastrointestinal carcinomas and recognizes a carbohydrate determinant (CA 19-9) defined as a sialylated lacto-N-fucopentaose II. A scheme was devised for the purification of a human gastrointestinal tumor-associated glycoprotein antigen expressing CA 19-9 from colorectal carcinoma cell line SW1116 culture media in high yield. The key steps in the purification were immunoaffinity column chromatography with Mab 19-9 followed by reduction and alkylation of the specifically bound proteins in the presence of 6 M guanidine hydrochloride and a second Mab 19-9 immunoaffinity fractionation.