75N95020Q00205

The service is to support an ongoing DPI project, finding inhibitors of nicotinamide N-methyltransferase (NNMT) for treating ovarian cancer. This project is in collaboration with a physician scientist PI at the University of Chicago, partially supported by the NCI Chemical Biology Consortium program. The project team has identified a few lead compounds that are highly potent in the biochemical and cellular settings. The basic research conducted at the University of Chicago has indicated that this enzyme NNMT has a key role in promoting cancer metastasis and has the potential to be a therapeutic target for treating metastatic ovarian cancers. However, the key question remains to be answered is whether the NNMT inhibitors we discovered would stop or slow down tumor progression in animals, and eventually in humans. To answer this critical question, the project team has developed ovarian cancer animal models and is planning to treat those animals with our inhibitors for an extended period of time, so called “the efficacy study”. The planned studies will provide the important proof of concept results to support NNMT as a validated drug target, an important part of our mission at the NCATS. To do so, we’ll need 10 gram of a key chiral intermediate to support the synthesis of the lead compounds. Toward this goal, we’ll need a technique called chiral separation that separates a mixture of two compounds that are mirror images of each other at the molecule level. We’ll provide the mixture, called racemic compound, to the service vendor, and the vendor will carry a chiral separation using chiral liquid chromatography to separate the two respective compounds called enantiomers. The two pure enantiomers will be returned back to the NCATS, and the project team will take them forward to complete the synthesis of our final compounds for the efficacy study.