Mark S. Cushman was born in Fresno, California, on August 20, 1945. Dr. Cushman completed pre-pharmacy studies at Fresno State College (1963–1965) before enrolling as a University of California Regents Scholar in the School of Pharmacy at the University of California, San Francisco (UCSF), where he received the Pharm.D. degree in 1969. He continued at UCSF as a graduate student and was awarded the Ph.D. degree in medicinal chemistry in 1973. Dr. Cushman subsequently studied in Professor George Buchi's laboratory at the Massachusetts Institute of Technology from 1973–1975 as a National Institutes of Health Postdoctoral Fellow, and he then joined the faculty at the Purdue University College of Pharmacy in 1975, where he has served his entire independent academic career, and where he is now a Distinguished Professor Emeritus of Medicinal Chemistry. Dr. Cushman has taught a wide variety of courses to undergraduate students, graduate students, pharmacy students, and medical students, including organic chemistry, medicinal chemistry, and pharmacology.He has served as major professor for 39 Ph.D. graduate students, mentored 59 postdoctoral students, and hosted 5 international visiting scholars. Dr. Cushman's research focused on the design and synthesis drugs, ligands, and mechanism probes of a wide variety of macromolecular targets, includinglumazine synthase, riboflavin synthase, HIV gp120, HIV gp41, protein tyrosine kinases, HIV protease, HIV integrase, tubulin, HIV reverse transcriptase, topoisomerases I and II, EGFR, estrogen receptor-a, estrogen receptor-b, aromatase, sindbis virus capsid protein, quinone reductase I, quinone reductase II, retinoid X receptor, P21, flavivirus envelope protein, MAPK, tyrosyl-DNA phosphodiesterase I, tyrosyl-DNA phosphodiesterase II, ribosome, DNA, inorganic pyrophosphatase, ERK, JAKS 1-3, TYK2, and theMycpromoter G-quadruplex.His research is documented in 350 peer-reviewed scientific journal articles and 42 patents, and it has resulted in the design and synthesis anticancer, antiviral, and antimicrobial drugs and mechanism probes aimed at more than thirty macromolecular targets.Three anticancer drugs that were designed and synthesized in his laboratory at Purdue [indotecan (LMP 400), indimitecan (LMP 776), and LMP 744] have completed Phase I clinical trials. His research also resulted in the application of the Castagnoli-Cushman reaction to the total synthesis of a wide variety of protoberberine and benzophenanthridine alkaloids and anticancer drugs. Dr. Cushman served on the Editorial Advisory Boards of The Journal of Organic Chemistry (1999–2004) and The Journal of Medicinal Chemistry (2005–2010), and he was Associate Editor of the Journal of Medicinal Chemistry (2012–2020). Dr. Cushman served as a Senior Fulbright Scholar at Munich Technical University from 1983–1984, where he started an extensive investigation in Professor Adelbert Bacher's laboratory on the design and synthesis of mechanism probes that revealed key aspects of the biosynthesis of riboflavin (vitamin B2)
August 22nd, 2024 - Dr. Dennis Liotta
- In his decades-long career at Emory University, Dr. Dennis Liotta has drastically improved the longevity and quality of life of millions worldwide. These impressive accomplishments are not limited to just one significant discovery, as he has been directly involved in the discovery and development of multiple life-saving therapeutic agents. As a successful entrepreneur and visionary leader, he has created or fostered many businesses in the biotech and pharmaceutical industry. He has also pioneered new approaches to drug development in academia. All these achievements attest to his exceptional contributions to improving human health.
- Dr. Liotta is a world-renowned medicinal chemist and an innovator in drug discovery. His research focuses on the discovery and development of novel antiviral, anticancer, and anti-inflammatory therapeutic agents. To date, he has authored more than 300 peer-reviewed publications, cited by scientists around the globe tens of thousands of times. These publications fundamentally shaped modern medicinal chemistry and profoundly influenced countless young researchers.
- Dr. Liotta holds inventorship to over 100 issued patents in the U.S. alone and has more than 20 patent families currently under prosecution. He is the recipient of the 2022 Perkin Medal, generally considered to be the highest award for achievements in applied chemistry. He was elected to the National Academy of Inventors in 2014 and the Medicinal Chemistry Hall of Fame in 2010.
- Dr. Liotta’s innovations have resulted in 18 life-saving FDA-approved antiviral therapeutics. These include Atripla®, Biktarvy®, Combivir®, Complera®, Delstrigo®, Descovy®, Dutrebis®, Emtriva®, Epivir®, Epivir-HBV®, Epzicom®, Genvoya®, Odefesey®, Stribild®, Symtuza®, Triumeq®, Trizivir®, and Truvada®.
August 28th, 2023 - Dr. Richard Silverman
- Inhibition of Protein Aggregation and the Development of NU-9 for Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases
- Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease in which the motor neuron circuitry progressively degenerates, affecting mostly motor neurons in the brain (upper motor neurons) and spinal cord (lower motor neurons). There are no effective cures, although three drugs, riluzole, edaravone, and AMX0035, have been FDA approved, but with limited improvement in patients. Death generally occurs within 2-5 years from disease diagnosis. About 10% of patients have familial ALS (hereditary; fALS) and the remainder have sporadic ALS (sALS) with no known genetic cause. Greater than 150 gene mutations have been identified in fALS.
- Protein aggregation is a hallmark of all neurodegenerative diseases. We carried out a phenotypic high-throughput screen to identify compounds that inhibited protein aggregation caused by mutation of the sod1 gene, which leads to ALS in about 2% of ALS patients. Screen hits were filtered computationally, and three hit series were optimized.
- In this lecture, I discussed the development of two of these lead series, leading to two advanced compounds, for which one we have identified its target and the other, called NU-9, has been subjected to numerous preclinical studies related to efficacy, pharmacokinetics, and toxicology, and IND approved by FDA. The standard mouse model is used to show life extension by compound treatment; however, there is no translation from success in this mouse model and in patients. Therefore, we have taken a different approach, one that interogates the effectiveness of compounds to improve the health of the upper motor neurons in mouse models, which we anticipate should translate to patient efficacy. Preclinical results with NU-9 toward the treatment of ALS and Alzheimer’s disease will be presented.