Janet Rideout

Janet Rideout is an American organic chemist and one of the scientists who discovered that azidothymidine (AZT) could be used as an antiretroviral agent to treat Human Immunodeficiency Virus (HIV). Initially located in Tuckahoe (village), New York, the branch moved to Research Triangle, North Carolina, in 1970. As such, they're needed for replication (copying of the genome before cells divide so that each gets a copy). Therefore, cells that replicate frequently, such as cancer cells and bacteria have a high demand for nucleosides. Recognizing this, teams of scientists, including a team at Burroughs Wellcome including Janet Rideout dedicated themselves to studying chemical analogs that could mimic natural nucleosides, inhibiting replication.

The promising results from diaminopurine arabinoside led Rideout to synthesize additional purine arabinosides, in hopes of developing more effective antivirals. She worked with a team including virologists J. Bauer and P. Collins to study their pharmacological properties, discovering that aminopurine arabinosides had antiviral activity that was dependent on their amino group.

AZT Rideout also studied nucleosides' antibacterial properties. One of the compounds that interested her was azidothymidine (AZT), identical to the canonical nucleoside thymidine found in DNA except for the 3' position, where AZT has an azide (N3) group instead of a hydroxyl (OH) group. That 3' OH is needed for linking nucleotides together, so AZT could potentially act as a chain terminator (it could be added to a growing nucleic acid chain, but additional nucleotides couldn't link to it).

AZT was first synthesized in 1964 by a Michigan Cancer Foundation researcher, Jerome Horwitz, with hopes it could be used to treat leukemia, but it wasn't found to be effective and raised toxicity concerns so it was abandoned. There was limited research on it in the following years, including a report from a laboratory in showing it had activity against Friend virus, a murine virus that causes leukemia in mice, The compound was particularly effective against gram-negative bacteria. In addition to chemical characterization and optimization of its synthesis, their research included pharmacokinetic and safety testing in rats. with the screening carried out by virologist Martha (Marty) St. Clair.

One of the compounds Rideout chose to test was AZT and by the end of 1984, Wellcome had shown that AZT was active against two animal retroviruses, Harvey sarcoma virus and Friend leukemia virus. NCI found AZT to be highly effective against HIV in these cells,

Rideout's research on AZT didn't stop with its initial application to HIV. In the coming years at Burroughs Wellcome, she helped elucidate how AZT is processed in the body (administered as the cell membrane-permeable nucleoside, it is phosphorylated inside cells to the nucleotide form which is used in DNA synthesis) and how it selectively targets HIV's reverse transcriptase. She also continued to look into AZT's other potential uses, including against other viruses and bacteria.

Later career In 1995, after working at Burroughs Wellcome for over 26 years, and rising to the rank of associate division director, Rideout joined Inspire Pharmaceuticals (acquired by Merck in 2011) as Director of Chemistry. She subsequently had a number of promotions within the company: to Senior Director of Discovery in June 1996, Vice President in January 1998, and Senior Vice President of Discovery in February 2000.

Rideout retired in September 2000.

Rideout holds over 40 U.S. patents. In addition to the patent for treating HIV with AZT, she holds patents for synthesis procedures of various nucleoside analogs as well as their specific therapeutic applications; this includes derivatives of AZT for use treating and preventing infection by certain retroviruses and gram-negative bacteria. State University of New York, Buffalo Alumni Association, Distinguished Alumni Award, March 2014 Life fellow and member of board of directors, American Institute of Chemists

Selected publications