Dirofilaria immitis (heartworm) is a filarial worm that infects dogs and can cause congestive heart failure leading to death. Heartworm, transmitted by mosquitoes, is the most important parasite of dogs in the United States, and has spread to all states. There is no vaccine against heartworm, and current drugs in use have only modest effect, and are prone to complications. Therefore, it is urgently crucial that new effective and safe drugs are developed for treating heartworm infection in dogs. Investigators have identified and characterized a unique and potentially essential enzyme (herein called DiMT) in heartworm. This project’s goal is to identify inhibitors for the activity of DiMT and determine their efficacy in killing the parasite. Because DiMT is not found in dogs, validated DiMT inhibitors can ultimately be used as lead-compounds for potentially developing a novel class of drugs for effective and safe treatment of heartworm infections in dogs.