Shaomeng Wang
University of Michigan, MI·Pharmacology
Some proteins that drive cancer have long been considered "undruggable" because they have no good pocket for a drug to grip. A newer strategy sidesteps this problem: instead of blocking a protein, small molecules can tag it for destruction by the cell's own disposal machinery.
- Fields
Pharmacology
Chemistry
Medicine & Clinical Research
- Topics
targeted protein degradation
degrader
p300
- Grants
- 2 known grants, through Feb 2029
What they work on
- Optimize orally active small-molecule degraders that destroy both CBP and p300, paired histone acetyltransferases that switch on gene programs, and test them as a therapy for advanced, castration-resistant prostate cancer in mouse models.
- Compare the designed CBP/p300 degraders with conventional CBP/p300 inhibitors for potency in degrading the proteins and blocking tumor cell growth, and establish oral bioavailability and tolerated dosing schedules in mice.
- Design and synthesize improved PROTAC degraders of STAT5, a transcription factor hyperactive in leukemia, guided by co-crystal structures of ligands and degraders bound to STAT5.
- Test the in vitro activity, selectivity and mechanism of new STAT5 degraders across human cancer cell lines carrying different levels of activated STAT5, including CML and AML lines.
- Determine the metabolic stability, pharmacokinetics, pharmacodynamics, antitumor efficacy and potential toxicity of STAT5 degraders in mouse models to select a candidate for advanced preclinical development.
More about the research
These molecules, often built as PROTACs (two-headed compounds that tether a target protein to the cell's protein-shredding system), are called degraders. Two projects apply this approach to different cancer-driving proteins, with the same goal in both: pills that can be taken by mouth, that wipe out the target protein in tumors, and that are ready for clinical testing.
Why it matters
Prostate cancer remains the second leading cause of cancer death in North American men, and metastatic castration-resistant disease has few effective options; leukemias driven by hyperactive STAT5 are similarly hard to treat. Orally active degraders of CBP/p300 and the first-in-class STAT5 degraders could become new classes of therapy for these cancers, and if they hold up in preclinical testing they may advance to clinical trials.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Susan Logan
New York University, NY·Pharmacology
Test whether macrocycle 13, a synthetic ring-shaped molecule designed to block beta-catenin from binding its DNA partner TCF, suppresses Wnt/beta-catenin signaling in in vivo models of castration-resistant prostate cancer.
Jaewon Chang
Emory University, GA·Chemistry
Design and synthesize covalent warheads that react with lysine, tyrosine and serine residues on E3 ubiquitin ligases, the enzymes that tag proteins for destruction, going beyond the cysteine-reactive chemistry used so far.
Herman Sintim
University of Notre Dame, IN·Chemistry
Biochemically characterize second-generation 3H-pyrazolo[4,3-f]quinoline kinase inhibitors and use new chemistry to make third-generation compounds with better drug-like properties that target FLT3, CDK2, CDK12/13 or CDK18.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
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