Provided herein are integrin antagonists and methods of using the same. For example, one or more of the compounds or polypeptides provided herein can be used in the treatment of disorders such as heart attacks, stroke, and cancer metastasis. Also provided herein is a crystal comprising αvβ3 ectodomain complexed with inhibitor knottin 2.5 F. Further provided herein is a crystal comprising αVβ3 ectodomain complexed with inhibitor hFN10. In another aspect, the invention features a method that includes using a three-dimensional model of a complex that includes an integrin ectodomain.