Yale University

New Haven, Connecticut
Sterling Professor of Chemistry


Dr. Jorgensen’s research focuses on the discovery of drugs for cancer chemotherapy. He is a renowned expert in developing and applying the requisite methodology and computer software for computer-aided drug design. His team of experts are designing drugs that bind tightly to enzymes (protein molecules that catalyze reactions) involved in aberrant cell proliferation. The tight binding causes the enzymes to stop functioning, the cancer cells to stop reproducing, and the tumors to shrink. Such drugs are called enzyme inhibitors. Specifically, his research has sought inhibitors of an enzyme called fibroblast growth factor receptor 1 kinase (FGFR1 kinase). Aberrant FGFR kinase activity has been implicated in numerous cancers including breast cancer, human pancreatic cancer, astrocytomas, salivary gland adenosarcoma, Kaposi’s sarcoma, ovarian cancer, and prostate cancer. Therefore, discovery of inhibitors of FGFR1 kinase has substantial potential therapeutic value.

His team computationally modeled millions of compounds that might be possible FGFR1 kinase inhibitors and 23 compounds were purchased and experimentally tested. Two of the compounds showed some inhibitory activity towards FGFR1 kinase and his team focused on improving the potency of the compounds and their chemical properties to make them more likely to become drugs. Their work required the preparation (“synthesis”) of modified versions, “analogs”, of the initial “lead” compounds. They explored various changes in the series of thienopyrimidinone compounds and simplified the structures to only pyrimidinones which are uncommon as kinase inhibitors and were active at low micromolar concentrations. Future research will focus on enhancing the activity of these compounds and testing for selectivity in inhibiting other kinases.


Dr. William Jorgensen received his B.A. from Princeton University and his Ph.D. from Harvard University. In 1975, he first joined the faculty at Purdue University and in 1990, he joined the faculty at Yale University as the Whitehead Professor of Chemistry. He served as Director, Division of Physical Sciences & Engineering and he is currently the Sterling Professor of Chemistry.

From 2005 to 2010 at Yale University, Dr. Jorgensen co-directed the NFCR Center for Anti-Cancer Drug Design and Discovery with Director and NFCR-supported scientist, Dr. Alanna Schepartz. He is an elected member of the National Academy of Sciences and a Fellow of the American Chemical Society. Dr. Jorgensen is the recipient of numerous awards including; the ACS Award for Computers in Chemical and Pharmaceutical Research; Award in Computational Biology – International Society for Quantum Biology and Pharmacology; the Hildebrand Award in the Theoretical and Experimental Chemistry of Liquids (ACS); and the Tetraheron Prize.

He has published over 400 articles in the field of computational chemistry. He and his lab have developed software and computer modeling programs for drug design including TIP3P and TIP4P water models, the OPLS force field, and on free-energy perturbation theory for modeling reactions and molecular recognition in solution. Dr. Jorgensen’s service to the community includes numerous advisory boards in government and industry and journal editorial boards. He has been the Editor of the ACS Journal of Chemical Theory and Computation since its founding in 2005.

Related Content

NFCR In the News: Addressing Deadly Brain Cancer, GBM

Detecting Skin Cancer with Artificial Intelligence and Other Game-Changing Technologies in Cancer

Cases of skin cancer are skyrocketing. In the past three decades, more people have been diagnosed with some form of skin cancer than all other cancers combined. Because of this, researchers worldwide have been fascinated with figuring out how to better detect and treat skin cancer. The fascination has launched some of the world’s brightest scientists into innovation overdrive. The result? Artificial Intelligence to detect skin cancer.  Artificial Intelligence and Cancer Artificial Intelligence (AI) involves teaching technology to do tasks previously done by humans. It can be an Alexa device telling a joke, Google Home turning the lights on or off, or something more complex like analyzing medical data. Typically, information like X-Rays or CT scans would be read, reviewed, and analyzed by medical teams to identify abnormalities. Today, AI is used to quickly translate an image into data, compare that data against a more extensive set of normal and abnormal images, and produce a quantitative assessment of potential abnormalities. This method not only reduces the chance of human error but speeds up the process tenfold. Fewer errors and quicker diagnoses mean a far better chance of treating cancer in an early stage.  Innovative Cancer Technologies While the use of AI feels exceptionally futuristic, innovative technology has been emerging from the cancer field for years. In 2017, the U.S. Food and Drug Administration approved a bright pink liquid known as 5-ALA for brain cancer treatment. This drink, often referred to as ‘pink drink,’ is a surgical intervention drug given to brain cancer patients ahead of their surgeries. The pink drink makes brain tumor cells illuminate a hot pink color under fluorescent light when paired with the right technology.  Previous treatment for brain cancer was resection of the tumor. However, physicians alone were historically insufficient or incompletely identified tumor tissue during surgery, which led to recurrence and the abysmal survival rate of 1-2 years on average. Aided by the brilliant pink hues induced by 5-ALA, doctors can now remove and identify significantly more of the tumor.  In 2020, an NFCR funded team of renowned researchers explored how technology could improve treatment outcomes for patients with T-cell non-Hodgkin’s lymphoma. Before this study, professionals agreed that a molecule called fenretinide would, in theory, be able to treat non-Hodgkin’s lymphoma. However, it was seemingly impossible to deliver this molecule to cancer cells because it is poorly soluble in water. The NFCR-funded research team developed a unique delivery system to solve this issue, thus improving outcomes for lymphoma patients.  Accelerating Promising Cancer Research It is discoveries like these launch medical professionals forward towards finding a cure for cancers. NFCR proudly presents the Salisbury Award Competition, which helps oncology startups accelerate their findings to benefit the cancer community. This program offers a unique opportunity for other promising research deemed high-risk, high-impact ideas, a core value of NFCR’s.  NFCR will host the fourth Salisbury Award Competition later this year, with applications opening in March to academic laboratories advancing promising experimental cancer therapeutic, diagnostic, detection, and vaccine innovations.  Learn more about the Salisbury Award or apply to the program here.   Additional Reads You May Enjoy:  Salisbury Award: Providing […]

The World’s First Oncolytic Virus Drug was Launched to Treat Malignant Brain Tumor GBM

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor in adults, with a median survival of only about ten months. Unlike low-grade gliomas (grades I and II), which grow slowly, high-grade gliomas (grades III and IV) grow much faster and can spread to other parts of the brain, resulting in a patient’s death. GBM is the highest grade brain tumor (grade IV) with a very poor prognosis. The standard treatment for GBM includes surgery, radiation, and chemotherapy. However, these limited treatment approaches cannot control the tumor progress, and the rate of brain tumor recurrence is high, resulting in low overall survival (OS) in most patients.   Oncolytic Virus Therapy  Oncolytic virus therapy represents a new promising cancer immunotherapy approach that utilizes genetically modified viruses to infect and kill cancer cells. The viruses are modified to selectively infect and lyse cancer cells through genetic engineering processes while leaving normal cells unharmed. The genetic modification of the viruses also grants them the ability to produce immune-boosting molecules or initiate anti-cancer immunity through multiple mechanisms of the patient’s own immune system.  The First Oncolytic Virus Therapy for GBM  Recently, the world’s first oncolytic virus-based immunotherapy (Teserpaturev) was approved in Japan. Teserpaturev offers a new option for treating GBM and brings new hope to thousands of patients suffering from this malignant brain tumor.  Teserpaturev is a genetically engineered herpes simplex virus type 1 (HSV-1). The uniqueness of this new oncolytic virus-based drug is that it not only has strong killing power to brain tumor cells that the virus entered into, but it is also able to kill the tumor cells that have spread to other parts of the brain. This process happens by inducing systemic antitumor immunity of a patient’s own immune system.  In June 2021, Teserpaturev received a conditional and time-limited marketing approval in Japan to treat malignant glioma based on a Japanese phase 2 clinical trial in patients with GBM. The clinical trial results showed that 92% of patients who received Teserpaturev immunotherapy treatment were still alive after one year. This percent is considerably higher than the typical 15% one-year survival rate in this group of patients receiving standard late-stage brain tumor treatments.  Bottom Line Because Teserpaturev is currently under conditional and time-limited marketing approval in Japan, this novel immunotherapy for GBM is only available at specified hospitals in Japan. We hope international multi-center clinical trials on this innovative drug can take place in the near future. Hopefully, the novel therapy can be made available to GBM patients around the world.  Stay up-to-date with the latest information on new drug development. Receive our monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips, and more; sign up here.  Additional Reads You May Also Enjoy: Treating Brain Cancer: What You Need to Know New Brain Scan Technology Can Improve Tumor Removal GBM AGILE – Changing the Way We Fight Brain Cancer References Daiichi Sankyo introduces Delytact in Japan to treat malignant glioma. com, November 2, 2021.  http://www.pharmabiz.com/NewsDetails.aspx?aid=143694&sid=2 First launch for Daiichi Sankyo’s oncolytic virus Delytact in Japan. Pharmaphorum, November 1, 2021.  https://pharmaphorum.com/news/first-launch-for-daiichi-sankyos-oncolytic-virus-delytact-in-japan/