Positions
- Professor
-
Pharmacology and Chemical Biology
Baylor College of Medicine
Houston, TX US
- Faculty Senator
-
Baylor College of Medicine
Houston, Texas United States
- Member
-
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- Post-Doctoral Fellowship at University Of Illinois, Urbana-Champaign
- 01/2003 - Urbana, Illinois United States
- Post-Doctoral Fellowship at Tokyo Institute Of Technology
- 01/2001 - Tokyo, Japan
- PhD from National University Of Singapore
- 10/2000 - Singapore, Singapore
Professional Interests
- Drug Discovery, Medicinal Chemistry and Chemical Biology
Professional Statement
We are interested in discovery and development of novel small molecule inhibitors of biologically important proteins, targeting cancer and infectious diseases. These compounds will be used as chemical probes to find new cancer biology (Chemical Biology), or further developed to become clinically useful drugs (Drug Discovery). These goals will be achieved by using a combination of rational, computational drug design, synthetic chemistry, protein x-ray crystallography, high-throughput screening, biological activity testing, and molecular and cell biology.Our currently active projects include
1. Novel chemical probes targeting epigenetic (histone/DNA modification) proteins: We have recently discovered novel inhibitors of histone H3-lysine79 (H3K79) methyltransferase DOT1L, H3K4 demethylase LSD1, and histone acetyltransferase p300/CBP. These compounds were found to have selective activity against MLL-rearranged leukemia and other cancers. We are actively exploring functions of several other epigenetic proteins in cancer, designing and synthesizing potent and selective inhibitors as potential therapeutics.
2. Drug discovery targeting Zika and Dengue viruses, which are important human pathogens. Through compound screening followed by medicinal chemistry, a novel series of compounds were identified, for the first time, to be potent and drug-like inhibitors of Zika and Dengue virus proteases. These compounds exhibited potent in vitro and in vivo antiviral activity. Optimization of activity as well as drug properties is on-going, in an effort to find drug candidates to prevent and treat Zika and Dengue infections.
3. Chemical probes targeting cancer-associated gene mutations: Genetic studies show that a high frequency of IDH (isocitrate dehydrogenase) mutation was identified in glioma (75%), AML (20%) and other types of cancer. Biochemical studies as well as clinical evidence suggest IDH mutation plays important roles in cancer initiation and/or progression. We are using a combination of chemical, biophysical and molecule and cell biology methods to develop novel chemical probes targeting IDH mutation and investigate cancer biology of mutant IDH.
Websites
Selected Publications
- Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, Prasad BV, Song Y "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies.." J. Am. Chem. Soc.. 2011 October 26; 133 (42): 16746-9. Pubmed PMID: 21936531
- Zheng, B.; Yao, Y.; Liu, Z.; Deng, L.; Anglin, J. L.; Jiang, H.; Prasad, B. V. V.; Song, Y. "Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase." ACS Med. Chem. Lett.. 2013 4 : 542-546. Pubmed PMID: 23795241
- Xue, J.; Diao, J.; Cai, G.; Deng, L.; Zheng, B.; Yao, Y.; Song, Y. "Antimalarial and Structural Studies of Pyridine-containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase." ACS Med. Chem. Lett.. 2013 4 : 278–282. Pubmed PMID: 23795240
- Zhang, L.; Deng, L.; Chen, F.; Yao, Y.; Wu, B.; Wei, L.; Mo, Q.; Song, Y. "Inhibition of Histone H3K79 Methylation Selectively Inhibits Proliferation, Self-renewal and Metastatic Potential of Breast Cancer." Oncotarget. 2014 5 : 10665-77. Pubmed PMID: 25359765
- Liu, Z.; Yao, Y.; Kogiso, M.; Zheng, B.; Deng, L.; Qiu, J. J.; Dong, S.; Lv, H.; Gallo, J. M.; Li, X.-N.; Song, Y. "Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases: Synthesis, SAR and Selective Antitumor Activity." J. Med. Chem.. 2014 57 : 8307-18. Pubmed PMID: 25271760
- Wu, F.; Zhou, C.; Yao, Y.; Wei, L.; Feng, Z.; Deng, L.; Song, Y. "3-(Piperidin-4-ylmethoxy)pyridine Containing Compounds Are Potent Inhibitors of Lysine Specific Demethylase 1.." J. Med. Chem.. 2016 59 : 253. Pubmed PMID: 26652247
- Wu, F.; Zheng, B.; Jiang, H.; Kogiso, M.; Yao, Y.; Zhou, C.; Song, Y. "Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds.." J. Med. Chem.. 2015 58 : 6899. Pubmed PMID: 26280302
- Feng, Z.; Zhou, C.; Wu, F.; Yao, Y.; Wei, L.; Liu, W.; Dong, S.; Redell, M.; Song, Y. "Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia.." J. Hematol. Oncol.. 2016 9 : 24. Pubmed PMID: 26970896
- Lu, L.; Wen, Y.; Yao, Y.; Chen, F.; Wang, G.; Wu, F.; Wu, J.; Narayanan, P.; Redell, M.; Mo, Q.; Song, Y. "Glucocorticoids Inhibit Oncogenic RUNX1-ETO in Acute Myeloid Leukemia with Chromosome Translocation t(8;21).." Theranostics. 2018 8 : 2189.
- Yao, Y.; Huo, T.; Lin, Y.-L.; Nie, S.; Wu, F.; Hua, Y.; Wu, J.; Kneubehl, A. R.; Vogt, M. B.; Rico-Hesse, R.; Song, Y. "Discovery, X-ray Crystallography and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease." J. Am. Chem. Soc.. 2019 141 : 6832-6836. Pubmed PMID: 31017399
- Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, Cheng G, Chen P, Dong S, Song Y "Synthesis and Structure-Activity Relationship Investigation of Adenosine-Containing Inhibitors of Histone Methyltransferase DOT1L.." J. Med. Chem.. 2012 September 27; 55 (18): 8066-74. Pubmed PMID: 22924785
Projects
- Chemical probes targeting cancer-associated gene mutations
- Drug discovery and mechanistic studies targeting epigenetic proteins
- Drug Discovery Targeting Zika and Dengue Viruses
Funding
- Drug Discovery and Mechanistic Studies of Protein Methylation Targeting Leukemia - #RP150129 (PI) Grant funding from CPRIT
- Antiviral Drug Discovery Targeting Zika Virus Protease - #W81XWH-18-1-0368 (PI) Grant funding from DOD/CDMRP
- Novel Small Molecule Probes Targeting Histone Acetyltransferase p300/CBP - #RP180177 (PI) Grant funding from CPRIT
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