Our lab synthesizes and uses small molecules to understand the biology of disease and to produce more effective therapeutics.
In the UC San Francisco lab of Adam Renslo, PhD, scientists synthesize small organic molecules to better understand the biology of disease and to produce more effective therapeutics. “Small” molecules comprise the active ingredients of the majority of drugs used to treat human disease. The reason small molecules are so effective is that they are the correct size to interact with the enzymes and receptors that mediate biological processes, including disease.
An effective drug must possess a variety of favorable properties, including:
- Sufficient potency to exert the desired effect at a tolerable dose
- Selectivity for the desired biological target(s) over the multitude of other “off-targets” present in a complex organism
- Sufficient stability and persistence in the body so that the drug can reach its intended target
Solving this multifactorial problem is the job of the medicinal chemist. Prototype drug molecules are synthesized and evaluated in the test tube, in cells, and eventually in animals. The process is iterative and empirical, with each experimental result informing the design of improved leads. In the pharmaceutical industry, hundreds or thousands of leads are typically evaluated before a drug candidate ready for human clinical trials is identified. Academic laboratories are increasingly using small molecules to study the biology of disease and to help identify novel leads for drug discovery. Our lab's current efforts are focused in the following three areas:
- Iron dependent pharmacology – invention and applications of iron(II)-sensing prodrug technologies; antimalarial drug discovery
- Novel neuropharmacology – development of small molecule probes and leads to study and intervene in neurodegeneration, pain, and depression
- Lead discovery for infectious disease – application of fragment-based methods to identify drug leads for serious bacterial infections
Advances in genetic sequencing and computational and systems biology mean that a multitude of new biological targets and pathways are being discovered and their functions revealed. We aim to identify first-in-class molecules for emerging drug targets, exhibiting novel small molecule pharmacology.
Many of these discoveries about new biological targets and pathways are being made at UCSF by world-class researchers in systems and molecular biology. This deluge of new information has enormous potential to be translated into advances in treating human disease, if effective drugs can be identified for these novel targets.
However, whereas the vast majority of existing drugs target enzymes or receptors that naturally bind small molecules (e.g., G-protein-coupled receptors and kinases), finding small molecules that bind to protein-protein interfaces is a major challenge that remains very much a research problem. UCSF has a thriving research enterprise in the small molecule arena and is home to the Small Molecule Discovery Center, for which Renslo serves as co-director.
Thus, the confluence of new biological knowledge and a clear need for new approaches in small molecule discovery make UCSF an ideal place in which to pursue our research. As well, scientists in systems and molecular biology and small molecule discovery are physically located on the same UCSF research campus at Mission Bay, thus fostering conversation, insight, and collaboration across fields.
In addition, UCSF itself is a graduate-level-only institution with a singular focus on health. Within the campus, the School of Pharmacy, in which the Department of Pharmaceutical Chemistry and the Renslo Lab sit, focuses on improving health through therapeutics. Thus from lab to department to school to campus, UCSF is a rich and supportive environment for health science research, including innovative research dedicated to improving the world’s arsenal of therapeutics to prevent and treat disease.
The Renslo Lab comprises staff scientists, postdoctoral researchers, and graduate students. This combination suits the translational nature of our research and provides a stimulating environment for postdoctoral scholars and PhD students. Our staff scientists possess many years of medicinal chemistry experience, much of it gained in the pharmaceutical industry. The lab is fortunate to have attracted postdoctoral researchers from around the world and talented PhD students from the Chemistry and Chemical Biology Graduate Program at UCSF. More: People.