A Structure-Activity Relationship (SAR) Analysis for the Identification of Environmental Estrogens

Cunningham, Suzanne L.; Iype, Seena; Consoer, Daniel; Cunningham, Albert R.

doi:10.1201/9781420076363.ch7

Cited by 1 publication

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“…The cat-SAR approach is a computational SAR or in silico toxicity analysis and prediction “expert system.” In previous analyses, the cat-SAR program was able to achieve an overall concordance between observed and predicted values of 92% for a set of chemicals assessed for their ability to induce respiratory hypersensitivity [ 16 ], 80%–90% for a set of environmental estrogen mimics [ 17 ], and 78%–84% for a set of rat mammary carcinogens [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

Cunningham

Carrasquer

Mattison

2009

International Journal of Pediatric Endocrinology

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The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

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Section: Methodsmentioning

confidence: 99%