Daniel L. Purich – The Inhibitor Index (2017)

Описание

The roots of this reference book first took hold in 1967, when the purchase of a small notebook permitted me – then a first-year
graduate student at Iowa State University – to record the names and properties of every enzyme and metabolic inhibitor then in use
in the Department of Biochemistry & Biophysics. That practice was sparked by my graduate work in the laboratory of Professor
Herbert J. Fromm, the enzyme kineticist who pioneered the use of dead-end competitive inhibitors, alternative substrate inhibitors,
and multisubstrate geometrical analogues to define the steady-state behavior of multisubstrate enzyme-catalyzed reactions.
Although a famously demanding taskmaster, Herb never discouraged his students from visiting the Physical Sciences Reading
Room, and I spent many an hour reading research journals in quiet comfort, learning more and more about the primary modes of
action of countless inhibitors. During a visit to Ames several years later, the celebrated enzymologist Ephraim Racker presented
a seminar, in which he restated his oft-quoted and playful adage: “An inhibitor is most specific on the day of its discovery.” Little
did Racker know how he had inspired me to pay more attention to the off-target and toxic effects of inhibitors.
This systematic effort continued, when, as a NIH Staff Fellow, I joined Earl Stadtman in the NIH Laboratory of Biochemistry
to study the adenylylation/deadenylylation cascade that controls the Escherichia coli glutamine synthetase, an enzyme that is
unrivaled in the complexity of its feedback inhibition, posttranslational modification, and transcriptional regulation. As a mecca
for biomedical research, Earl and Terry Stadtman’s lab attracted many famous researchers, who were always eager to share their
latest findings. The Library in nearby Building 10 was also an ideal setting for me to add new compounds and to gather details
about the actions of inhibitors acting on all manner of biochemical and physiological processes.
This practice continued with heightened interest, when I moved to the Department of Chemistry at the University of California
Santa Barbara, where I filled the position and occupied the office previously occupied by the late Professor B. R. Baker, a pioneer
in the synthesis of puromycin and anti-folates. Baker was the author of The Design of AcTive siTe-DesigneD irreversible enzyme
inhibiTors. That seminal monograph described the logic of his determined efforts to synthesize and screen many hundreds of
potential anticancer agents.
In the early 1970s, the field of enzyme chemistry was also abuzz with new ideas about the nature of enzyme intermediates,
the action of mechanism-based inhibitors, the theory and design of first-generation transition-state inhibitors, as well as first recognition
of slow, tight-binding inhibitors. The nature of allosteric feedback inhibition was yet another focus of enzyme science in
that era.
Upon becoming the Chair of Biochemistry & Molecular Biology at the University of Florida College of Medicine in 1984, I
had the opportunity to attend numerous pharmacology, physiology, and neuroscience seminars, a practice that fostered greater
awareness of the clinical significance of receptor antagonists. A few years later, the department was fortunate to hire Dr. R. Donald
Allison as an instructor. Previously my doctoral student at UC Santa Barbara, Don was keenly aware of the “Inhibitor Project”,
and, in 2004, offered to consolidate my inhibitor database and to collect additional information. Tragically, that effort was cut
short in 2010, when Don perished from injuries from an auto accident. I dedicate this monograph to Don Allison in honor of our
37-year friendship. A better friend no one can have!
Now, fifty years after this project began, the first edition of The inhibiTor inDex will provide readers with a single-source reference
citing over 50,000 original research publications on the actions of nearly 8000 enzyme inhibitors, receptor antagonists,
drugs, toxins, poisons, and/or therapeutic leads. Many are widely used in research and medicine; others should stimulate novel
approaches and further research; still others are offered to acknowledge their historical significance. Future editions will include
additional entries from an already compiled master source list of over 12,000 compounds. Readers are advised that suggestions
for new entries and corrections will always be welcomed.
Lastly, I thank Fiona Macdonald at CRC Press for making the publication of this book so pleasant, even as she deftly applied
her considerable chemical prowess to detect and correct my errors.