Squishy Physics

Next seminar: Wednesday September 19th in Pierce 209 at 6 PM:


Development of small molecule inhibitors & probes for druggable targets


Wei Zhang, Ph.D. 

     Professor and Director for Center for Green Chemistry

 Department of Chemistry, University of Massachusetts Boston


Abstract: This presentation highlights our recent effort on the development of green and highly efficient methods for drug-like molecule synthesis and asymmetric catalysis. A series of technologies including fluorous technologies, multicomponent reactions, and organocatalysis are integrated to maximize reaction and separation efficiency in the synthesis of diverse heterocyclic scaffolds with substitution, skeleton, and stereochemistry variations. Through the collaboration with Harvard and other medical schools in US and Europe, our compounds have been integrated to a number of drug discovery programs. Several lead compounds have been developed for druggable targets such bromodomains (BET, CBP), kinases (PLK1), MDM2, PARP1&2, HIV-1, and RORgt targets which are related cancer, immune, inflammation and other diseases.



 Medichem-related Publications:

  • Liu, S.; Yosief, H. O.; Dai, L.; Huang, H.; Dhawan, G.; Zhang, X.; Muthengi, A. M.; Roberts, J.; Buckley, D.; Wu, L.; Bradner, J.; Qi, J.; Zhang, W. “Structure-guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) InhibitorsJ. Med. Chem. 2018, 61, 7785-7795.
  • Huang, H.; Liu, S.; Jean, M.; Huang, H.; Feeney, C.; Hayashi, T.; Kong, W.; Simpson, S.; Sanchez,I. R.; Zhang, X.; Yosief, H. O.; Miao, H.; Que, J.; Kobie, J.; Bradner, J.; Santoso, N.; Zhang, W.; Zhu, J. “A Novel Bromodomain Inhibitor Reverses HIV1 Latency Through Specific Binding with BRD4 to Promote Tat and PTEFb Association" Front. Microbiol. 2017, article 1035. 
  • Yang, G.; Buhrlage, S.; Li, T.; Liu, X.; Chen, J.; Xu, L.; Tsakmaklis, N.; Chen, J.; Patterson, C. J.; Brown, J.; Castillo, J. J.; Zhang, W.; Zhang, X.; Liu, S.; Cohen, P.; Hunter, Z. R.; Gray, N.; Treon, S. P. “HCK Is a Survival Determinant Transactivated by Mutated MYD88, and A Direct Target of IbrutinibBlood, 2016, 127, 3237-3252.
  • Bradner, J.; Buckley, D. L.; Ember, S.; Fitzgerald, M.; Koblan, L.; Liu, S.; Ott, C. J. T.; Roberts, J.; Schonbrunn, S.; Zhang, W. “Assessment of Bromodomain Target Engagement by a Series of BI2536 Analogues with Miniaturized BET-BRET” ChemMedChem 2016, 11, 2575-2581.
  • McKeown, M.; Shaw, D.; Fu, H.; Liu, S.; Xu, X.; Marineau, J.; Huang, Y.; Zhang, X.; Buckley, D.; Lin, C.; Kadam, A.; Zhang, Z.; Blacklow, S.; Qi, J.; Zhang, W.; Bradner, J. “Biased multicomponent reactions to develop novel bromodomain inhibitors” J. Med. Chem. 2014, 57, 9019-9027.
  • Zhu,J.; Larman, H. B.;Gao,G.; Somwar, R.; Zhang, Z.; Laserson, U;Alberto, C., A.; Pavlova, N.; Church,G.; Zhang, W.; Kesari, S.; Elledge, S. J. “Protein interaction discovery using parallel analysis of translated ORFs (PLato)” Nat. Biotechnol. 2013, 31, 331-334
  • Zhang, W. “Fluorous Linker-Facilitated Chemical SynthesisChem. Rev. 2009, 109, 749-795.


Prof. Wei Zhang is the Director of the Center for Green Chemistry at the University of Massachusetts Boston. He received his PhD and did his post-doctoral research at the University of Pittsburgh with late Prof. Paul Dowd. He had positions of Research Assistant Professor at the University of Pittsburgh, Senior Chemist at DuPont, and Director of Discovery Chemistry at Fluorous Technologies, Inc. (FTI). Prof. Zhang’s research is in the areas of green chemistry, fluorous chemistry, synthetic free radicals, organocatalysis, and medicinal chemistry. He has published over 190 papers including three Chem. Rev. and four Tetrahedron Reports, and the book “Green techniques for organic and medicinal applications” (Wiley 2012 & 2018). He is currently severing as editor and editorial advisory member on seven international journals including ACS Combinatorial Science and Green Processing and Synthesis. He received the International Fluorous Technology Award in 2015.



Squishy Physics & Pizza Seminar Series

When: Wednesday Evenings - Pizza served at 5:55 PM, talks start at 6 pm till...

Where: Room 209, Pierce Hall, 29 Oxford St, on the Harvard Campus. Directions and parking instructions are here.

What: These talks are informal, with emphasis on new results and ideas, rather than polished presentations. The Squishy audience members typically include soft matter scientists, physicists, engineers, chemists, and biologists.  The goal is to stimulate discussion with the audience.  Talks are typically about 45 minutes long, with lots of questions along the way.

Pizza: Only the finest! 

How to join the weekly Squishy Physics mailing list: please visit the Signup Page.

Directions: Where: Squishy Physics talks are held in Pierce Hall room 301, 29 Oxford Street, Cambridge, MA. See Harvard Campus map here.

Parking: Metered parking is available on Oxford Street.  Speakers, please contact Matthew Zahnzinger to obtain a parking permit.  

Squishy Physics is sponsored by the Cabot Corporation, Dean Cherry Murray and the Weitz Research Group.

If you have comments or suggestions or would like to give a talk, please contact Joerg Werner, Stefano Aime, or Perry Ellis.

Here is the upcoming schedule