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Dr. Larry Keefer, Ph.D.

Dr. Larry Keefer

International Leader in the Chemistry and Biology of Nitric Oxide

About Dr. Keefer

Dr. Larry Keefer joined the NCI in 1971 and spent the next 4 decades exploring the chemistry and biology of nitric oxide (NO) until his retirement in 2015. Dr. Keefer’s legacy includes over 300 publications, 51 patents and training many of today’s leaders in the field of chemistry.

What is Nitric Oxide?

Nitric oxide is a potent and multifaceted bioregulatory agent. Named “Molecule of the Year” by Science in 1992, NO was the focus of the 1998 Nobel Prize in Physiology or Medicine. Dr. Keefer’s research was aimed at targeting NO to specific sites in the body for important therapeutic applications using NO-releasing compounds called diazeniumdiolates (also known as NONOates). These agents have come into wide use as sources of authentic NO in research applications requiring reliable fluxes generated in solution with reproducible half-lives ranging from 2 seconds to 20 hours at physiological temperature and pH. Certain diazeniumdiolates were found to generate nitroxyl (HNO, the one-electron reduction product of NO and another known bioeffector) as well as NO on hydrolysis. Some potential clinical benefits of diazeniumdiolate technology are indicated below.

Diazeniumdiolate Chemistry as a Platform for Designing Nitric Oxide (NO)- and Nitroxyl (HNO)-based Clinical Applications

Four clinical areas in which diazeniumdiolate-based proof-of-concept studies suggest considerable practical significance on the part of this class of compounds. Central to the rational design of improved drugs and devices in all four of these areas was our vigorous program of basic research into the fundamental physicochemical properties of compounds bearing the diazeniumdiolate functional group.