Herman Sintim
University of Notre Dame, IN·Chemistry
Acute myeloid leukemia (AML) is a fast-growing blood cancer. Overall 5-year survival is about 30%, and 2-year survival for most patients over 60 is under 5%.
- Fields
Chemistry
Pharmacology
Biochemistry
- Topics
acute myeloid leukemia
triple-negative breast cancer
kinase inhibitors
- Grants
- 1 known grant, through Apr 2027
What they work on
- 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.
- Determine how lead compounds change protein phosphorylation in cancer cells and how potently they kill gilteritinib-resistant AML cell lines and triple-negative breast cancer cell lines.
- Evaluate the in vivo efficacy of lead compounds against acute myeloid leukemia and breast tumors in animal models to select preclinical candidates.
More about the research
About 30% of patients carry mutations in FLT3, an enzyme that drives cell growth, and they have the worst outcomes. Drugs that block FLT3 exist, but patients relapse as new FLT3 mutations and other escape routes appear. Triple-negative breast cancer (TNBC), a form that does not respond to hormone therapy, also has few treatment options. This project aims to develop new drug candidates against both cancers.
Why it matters
Patients with FLT3-mutated AML often relapse on current drugs, and those with triple-negative breast cancer have few options. This work aims to produce preclinical drug candidates against both diseases. Compounds that block CDK12/13 or CDK18, targets with no approved drugs, could also make tumors more sensitive to existing DNA-damaging chemotherapy or PARP inhibitors.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xiangshu Xiao
Oregon Health & Science University, OR·Pharmacology
Determine the mechanism by which a new small-molecule lead compound targets the RuvBL1/L2 protein complex to block DNA double-strand break repair in triple negative breast cancer cells.
Shaomeng Wang
University of Michigan, MI·Pharmacology
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.
Boaz Tirosh
Case Western Reserve University, OH·Pharmacology
Map the specific defect in mitochondrial respiration that appears when AML cells are treated with the mTORC1 activator AcTor plus a proteasome inhibitor, a drug that blocks protein disposal.
The school
University of Notre Dame: 19 labs on PI Pages, $346M a year on research, 277 research doctorates a year.
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