The Cernak Lab
The Cernak Lab
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Research

The Cernak Lab studies the interface of chemical synthesis and computer science. A small molecule’s structure encodes its function, so synthetic strategies that access diverse molecular structures are paramount to the invention of novel functional molecules such as dyes, agrichemicals, fragrances or pharmaceuticals. We use algorithms, robotics and data science to study new chemical reactions, synthetic routes to natural products, and biochemical probes. Our lab employs informatics to problems in reaction discovery, total synthesis, cell imaging, climate change and medicinal chemistry. By studying the relationship of chemical synthesis to functional properties, we pursue the opportunity to positively impact human and environmental health.

The Team

PI. Tim Cernak is an Assistant Professor of Medicinal Chemistry at the University of Michigan. He holds appointments in the University of Michigan Department of Chemistry, the Program in Chemical Biology, the Center for Global Health Equity, and the Michigan Institute for Data Science. Tim’s research interests include chemical synthesis, catalysis, total synthesis, chemoinformatics, data science, automation, natural products, medicinal chemistry, agrichemistry, sustainability, cell imaging, mass spectrometry, ecology, conservation, robotics and drug discovery. Prior to joining the University of Michigan in 2018, Tim worked for 9 years at Merck Research Laboratories in Rahway, NJ and Boston, MA where he focused on C–H functionalization, reaction miniaturization, and drug design for oncology, neurological and metabolic diseases. Tim performed undergraduate studies at UBC Okanagan, was an FQRNT Pre-doctoral Fellow at McGill University in the labs of Prof. Jim Gleason, and an FQRNT Post-doctoral Fellow at Columbia University with Prof. Tristan Lambert. Tim has served on the Advisory Board of The University of Dundee’s Drug Discovery Unit, The Open Reaction Database and Scorpion Therapeutics. He is a co-founder of Iambic Therapeutics.

[CV] [bio]

Publications

Andrew McGrath, Haiyan Huang, Jean-Francois Brazeau, Zirong Zhang, Nadeem A. Vellore, Lu Zhu, Zhicai Shi, Jennifer D. Venable, Christine Gelin, Tim Cernak. Diverse Amine-Acid Coupling Reactions Modulate the Potency of BRD4 PROTACs. ChemRxiv, 2023. [preprint]

Rui Zhang, Babak Mahjour, Andrew Outlaw, Andrew McGrath, Tim Hopper, Brian Kelley, W. Patrick Walters, Tim Cernak. Exploring the Combinatorial Explosion of Amine–Acid Reaction Space via Graph Editing. Communications Chemistry 2024, 7, 22. [preprint] [link]

Babak Mahjour, Andrew McGrath, Andrew Outlaw, Ruheng Zhao, Charles Zhang, Tim Cernak. Interactive Python Notebook Modules for Chemoinformatics in Medicinal Chemistry. Journal of Chemical Education 2023, ASAP [link]

Babak Mahjour, Jillian Hoffstadt, Tim Cernak. Designing Chemical Reaction Arrays using phactor and ChatGPT. Organic Process Research & Development 2023, 27, 1510–1516 [link] [preprint]

Babak Mahjour, Rui Zhang, Yuning Shen, Andrew McGrath, Ruheng Zhao, Osama G. Mohamed, Yingfu Lin, Zirong Zhang, James L. Douthwaite, Ashootosh Tripathi, Tim Cernak. Rapid Planning and Analysis of High-Throughput Experiment Arrays for Reaction Discovery. Nature Communications 2023, 14 (3924) [preprint1] [preprint2] [link]

Nathan Gesmundo, Kevin Dykstra, James Douthwaite, Yu-Ting Kao, Ruheng Zhao, Babak Mahjour, Ron Ferguson, Spencer Dreher, Berengere Sauvagnat, Josep Sauri, Tim Cernak. Miniaturization of Popular Reactions from the Medicinal Chemists’ Toolbox for Ultrahigh-Throughput Experimentation. Nature Synthesis. 2023 [link] [preprint]

Eunjae Shim, Ambuj Tewari, Tim Cernak, Paul Zimmerman. Machine Learning Strategies for Reaction Development Toward the Low-Data Limit. Journal of Chemical Information and Modeling. 2023, 63 (12) 3659–3668 [link]

James L. Douthwaite, Ruheng Zhao, Eunjae Shim, Babak Mahjour, Paul Zimmerman, Tim Cernak. The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3–sp2 Carbon–Carbon Bonds. Journal of the American Chemical Society. 2023, 145 (20), 10930–10937 [preprint] [link]

Yingfu Lin, Rui Zhang, Di Wang, and Tim Cernak. Computer-aided key step generation in alkaloid total synthesis. Science 2023, 379(6631), 453–457. [link]

Babak Mahjour, Jordan Bench, Rui Zhang, Jared Frazier, Tim Cernak. Molecular Sonification for Molecule to Music Information Transfer. Digital Discovery 2023, 2, 520–530 [link] [preprint] – Listen Here: [Vitamin B12] [Taxol] – Try converting molecules into music with SAMPLES [here].

Andrew McGrath, Rui Zhang, Khadija Shafiq, Tim Cernak. Repurposing amine and carboxylic acid building blocks with an automatable esterification reaction. Chemical Communications 2023, 59, 1026–1029. [link] [preprint]

Yuning Shen, Babak Mahjour, Tim Cernak. Development of copper-catalyzed deaminative esterification using high-throughput experimentation. Communications Chemistry 2022, 5(83). [link]

Eunjae Shim, Joshua A. Kammeraad, Ziping Xu, Ambuj Tewari, Tim Cernak, Paul M Zimmerman. Predicting reaction conditions from limited data through active transfer learning. Chemical Science. 2022, 13, 6655–6668. [link]

Yingfu Lin†, Zirong Zhang†, Babak Mahjour, Di Wang, Rui Zhang, Eunjae Shim, Andrew McGrath, Yuning Shen, Nadia Brugger, Rachel Turnbull, Shashi Jasty, Sarah Trice, Tim Cernak* “Reinforcing the Supply Chain of COVID-19 Therapeutics with Expert-Coded …

Yingfu Lin, Zirong Zhang, Babak Mahjour, Di Wang, Rui Zhang, Eunjae Shim, Andrew McGrath, Yuning Shen, Nadia Brugger, Rachel Turnbull, Shashi Jasty, Sarah Trice, Tim Cernak. Reinforcing the Supply Chain of Umifenovir and Other Antiviral Drugs with Retrosynthetic Software. Nature Communications 2021, 12, 7237. [link]

Zirong Zhang and Tim Cernak. The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3–sp3 Carbon–Carbon Bonds. Angewandte Chemie International Edition. 2021, 60(52), 27293–27298. [link]

Babak Mahjour, Yuning Shen, Tim Cernak. Ultrahigh-Throughput Experimentation for Information-Rich Chemical Synthesis. Acc. Chem. Res., 2021. [link]

Babak Mahjour, Yuning Shen, Tim Cernak. Ultrahigh-Throughput Experimentation for Information-Rich Chemical Synthesis. Accounts of Chemical Research 2021, 54(10), 2337–2346. [link]

Yuning Shen, Julia E. Borowski, Melissa A. Hardy, Richmond Sarpong, Abigail G. Doyle, Tim Cernak. Automation and computer-assisted planning for chemical synthesis. Nat Rev Methods Primers 1, 23 (2021). [link]

Yuning Shen, Julia E. Borowski, Melissa A. Hardy, Richmond Sarpong, Abigail G. Doyle, Tim Cernak. Automation and computer-assisted planning for chemical synthesis. Nature Reviews Methods Primers 2021, 1(23). [link]

Babak Mahjour, Yuning Shen, Wenbo Liu, and Tim Cernak*. “A map of the amine-carboxylic acid coupling system”, Nature, 2020, 580, 71–75. [link]

Babak Mahjour, Yuning Shen, Wenbo Liu, and Tim Cernak. A map of the amine-carboxylic acid coupling system. Nature 2020, 580, 71–75. [link]

Kun Liu, Ravi Kurukulasuriya, Kevin Dykstra, Lisa DiMichelle, Jinchu Liu, Petr Vachal, Anthony Ogawa, Robert J. DeVIta, Dong-Ming Shen, QIang Tan, Yili Chen, Don Gauthier, Andreas Verras, Alejandro Crespo, Beata Zamlynny, Jeffrey Madwed, Maarten Hoek, Thomas Bateman, Yun-Fang Yang, K.N. Houk, Tim Cernak. Development of Indazole Mineralocorticoid REceptor Antagonists and Investigation Into Their Selective Late-Stage Functionalization. Bioorganic & Medicinal Chemistry Letters 2019, 29(14) 1854–1858. [link]

Mycah R. Uehling, Ryan P. King, Shane W. Krska, Tim Cernak* and Stephen L. Buchwald*. “Pharmaceutical Diversification via Palladium Oxidative Addition Complexes”, Science, 2019, 363, 405—408. [link]

Mycah R. Uehling, Ryan P. King, Shane W. Krska, Tim Cernak and Stephen L. Buchwald. Pharmaceutical Diversification via Palladium Oxidative Addition Complexes. Science, 2019, 363, 405–408. [link]

Hazel Wong and Tim Cernak*. “Reaction Miniaturization in Eco-Friendly Solvents”, Curr. Opin. Green Sus. Chem., 2018, 11, 91—98. [link]

Hazel Wong and Tim Cernak. Reaction Miniaturization in Eco-Friendly Solvents. Current Opinion Green & Sustainable Chemistry. 2018, 11, 91–98. [link]

Shishi Lin, Sergei Dikler, Ronald D. Ferguson, Robert P. Sheridan, Zhengwei Peng, Donald V. Conway, Kerstin Zawatzky, Heather Wang, Tim Cernak, Ian W. Davies, Daniel A. DiRocco, Huaming Sheng*, Christopher J. Welch*, Spencer D. Dreher*, “Mapping the…

Shishi Lin, Sergei Dikler, Ronald D. Ferguson, Robert P. Sheridan, Zhengwei Peng, Donald V. Conway, Kerstin Zawatzky, Heather Wang, Tim Cernak, Ian W. Davies, Daniel A. DiRocco, Huaming Sheng, Christopher J. Welch, Spencer D. Dreher, Mapping the Dark Space of Chemical Reactions with Extended Nanomole Synthesis and MALDI-TOF MS. Science, 2018, 361, 1–7. [link]

Nathan J. Gesmundo, Bérengère Sauvagnat, Patrick Curran, Matthew P. Richards, Christine L. Andrews, Peter J. Dandliker, Tim Cernak*. “Nanoscale Synthesis and Affinity Ranking”, Nature, 2018, 557, 228—232. [link]

Nathan J. Gesmundo, Bérengère Sauvagnat, Patrick Curran, Matthew P. Richards, Christine L. Andrews, Peter J. Dandliker, Tim Cernak. Nanoscale Synthesis and Affinity Ranking. Nature, 2018, 557, 228–232. [link]

Tim Cernak*. “A Machine with Chemical Intuition”, Chem, 2018, 4(3), 401—403. [link]

Tim Cernak. A Machine with Chemical Intuition. Chem. 2018, 4, 401–403. [link]

Tim Cernak*, Nathan Gesmundo, Kevin D. Dykstra, Yang, Yu, Zhicai Wu, Zhi-Cai Shi, Petr Vachal, Donald Sperbeck, Shuwen He, Beth Murphy, Lisa Sonatore, Steven Williams, Maria Madeira, Andreas Verras, Maud Reiter, Claire Lee, James Cuff, Edward Sherer…

Tim Cernak, Nathan Gesmundo, Kevin D. Dykstra, Yang, Yu, Zhicai Wu, Zhi-Cai Shi, Petr Vachal, Donald Sperbeck, Shuwen He, Beth Murphy, Lisa Sonatore, Steven Williams, Maria Madeira, Andreas Verras, Maud Reiter, Claire Lee, James Cuff, Edward Sherer, Jeffrey Kuethe, Stephen Goble, Nicholas Perrotto, Shirly Pinto, Dong-Ming Shen, Ravi Nargund, James Balkovec, Robert DeVita, Spencer Dreher. Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors. J. Med. Chem. 2017, 60, 3594–3605. [link]

Tim Cernak*. “Synthesis in the Chemical Space Age”, Chem, 2016, 1(1), 6—9. [link]

Tim Cernak. Synthesis in the Chemical Space Age. Chem. 2016, 1, 6–9. [link]

Peter S. Kutchukian, James F. Dropinski, Kevin D. Dykstra, Bing Li, Daniel A. DiRocco, Eric C. Streckfuss, Louis-Charles Campeau, Tim Cernak, Petr Vachal, Ian W. Davies, Shane W. Krska* and Spencer D. Dreher*. “Chemistry Informer Libraries: A Chemoi…

Peter S. Kutchukian, James F. Dropinski, Kevin D. Dykstra, Bing Li, Daniel A. DiRocco, Eric C. Streckfuss, Louis-Charles Campeau, Tim Cernak, Petr Vachal, Ian W. Davies, Shane W. Krska and Spencer D. Dreher. Chemistry Informer Libraries: A Chemoinformatics Enabled Approach to Evaluate and Advance Synthetic Methods. Chem. Sci. 2016, 7, 2604–2613. [link]

Tim Cernak*, Kevin D. Dykstra, Sriram Tyagarajan, Petr Vachal and Shane W. Krska. “The Medicinal Chemist’s Toolbox for Late Stage Functionalization of Drug-Like Molecules”, Chemical Society Reviews, 2016, 45(3), 546—576. [link]

Tim Cernak, Kevin D. Dykstra, Sriram Tyagarajan, Petr Vachal and Shane W. Krska. The Medicinal Chemist’s Toolbox for Late Stage Functionalization of Drug-Like Molecules. Chem. Soc. Rev. 2016, 45, 546–576. [link]

Alexander Buitrago Santanilla, Erik L. Regalado, Tony Pereira, Kevin Bateman, Louis-Charles Campeau, Simon Berritt, Yong Liu, Michael Shevlin, Zhi-Cai Shi, Jonathan Schneeweis, Christopher J. Welch, Roy Helmy, Petr Vachal, Ian Davies, Tim Cernak* an…

Alexander Buitrago Santanilla, Erik L. Regalado, Tony Pereira, Kevin Bateman, Louis-Charles Campeau, Simon Berritt, Yong Liu, Michael Shevlin, Zhi-Cai Shi, Jonathan Schneeweis, Christopher J. Welch, Roy Helmy, Petr Vachal, Ian Davies, Tim Cernak and Spencer Dreher. Nanomolar-Scale High-Throughput Chemistry for the Synthesis of Complex Molecules. Science, 2015, 347, 49–53. [link]

Shuwen He,* Qingmei Hong, Zhong Lai, David X. Yang, Pauline C. Ting, Jeffrey T. Kuethe, Timothy A. Cernak, Kevin D. Dykstra, Donald M. Sperbeck, Zhicai Wu, Yang Yu, Ginger X. Yang, Tianying Jian, Jian Liu, Deodial Guiadeen, Arto D. Krikorian, Lisa M…

Shuwen He, Qingmei Hong, Zhong Lai, David X. Yang, Pauline C. Ting, Jeffrey T. Kuethe, Timothy A. Cernak, Kevin D. Dykstra, Donald M. Sperbeck, Zhicai Wu, Yang Yu, Ginger X. Yang, Tianying Jian, Jian Liu, Deodial Guiadeen, Arto D. Krikorian, Lisa M. Sonatore, Judyann Wiltsie, Jinqi Liu, Judith N. Gorski, Christine C. Chung, Jack T. Gibson, JeanMarie Lisnock, Jianying Xiao, Michael Wolff, Sharon X. Tong, Maria Madeira, Bindhu V. Karanam, Dong-Ming Shen, James M. Balkovec, Shirly Pinto, Ravi P. Nargund, and Robert J. DeVita. Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety. ACS Med. Chem. Lett. 2014, 5, 1082–1087. [link]

Heike Schönherr and Tim Cernak*. “Profound Methyl Effects in Drug Discovery and a Call for New C-H Methylation Reactions”, Angewandte Chemie International Edition in English, 2013, 52(47), 12256—12267. [link]

Heike Schönherr and Tim Cernak. Profound Methyl Effects in Drug Discovery and a Call for New C-H Methylation Reactions. Angewandte Chemie Internatioal Edition 2013, 52, 12256–12267. [link]

Timothy Cernak*, Kevin Dykstra, Dorothy Levorse, Andreas Verras, James Balkovec, Ravi Nargund and Robert DeVita. "Synthesis of Oxaspiropiperidines as a Strategy for Lowering logD", Tetrahedron Letters, 2011, 52(48), 6457—6459. [link]Lisa A. Ambrosin…

Timothy Cernak, Kevin Dykstra, Dorothy Levorse, Andreas Verras, James Balkovec, Ravi Nargund and Robert DeVita. Synthesis of Oxaspiropiperidines as a Strategy for Lowering logD. Tetrahedron Letters 2011, 52(48), 6457–6459. [link]

Lisa A. Ambrosini, Tim A. Cernak and Tristan H. Lambert. Total Synthesis of the Tylophora Alkaloids Rusplinone, 13aα-Secoantofine, and Antofine using a Multicatalytic Oxidative Aminochlorocarbonylation / Friedel-Crafts Reaction. Tetrahedron, 2010, 66(26), 4882–4887.


Lisa A. Ambrosini, Tim A. Cernak and Tristan H. Lambert. Development of Oxidative Formylation and Ketonylation Reactions. Synthesis, 2010, 41(28), 870–881.


Tim A. Cernak and Tristan H. Lambert. Multicatalytic Synthesis of α-Pyrrolidinyl Ketones via a Tandem Palladium(II)/Indium(III)-Catalyzed Aminochlorocarbonylation/Friedel-Crafts Acylation Reaction. The Journal of the American Chemical Society, 2009, 131(9), 3124–3125.


Jonathan Hudon, Timothy A. Cernak, James A. Ashenhurst and James L. Gleason. Stable 5-Substituted Cyclopentadienes for the Diels-Alder Cycloaddition and Their Application to Palau’amine Synthesis. Angewandte Chemie International Edition in English, 2008, 47, 8885–8888.


Timothy A. Cernak and James L. Gleason. DFT Guided Design of Exo-Selective Dehydroalanine Dienophiles for Application Towards Palau’amine. Journal of Organic Chemistry, 2008, 73(1), 102–110.


Timothy A. Cernak and James L. Gleason. Synthesis of 5-Chloromethylene Hydantoins and Thiohydantoins. Heterocycles, 2007, 71(1), 117–134.


Nigel J. Eggers, John D. Greenough, Tim Cernak. Classification of British Columbia’s Okanagan Chardonnay Wines by Origin Using Volatile Components, in Fine Wine and Terroir: A Geoscience Perspective ed. R. W. MacQueen, L. D. Meinert. Canada: St. John’s: Geological Association of Canada. 2006, 183–219.

 Software

phactor

a high throughput experimentation manager [link]

samples

a molecular sonification tool [link]

covidroutes

a retrosynthetic route visualizer [link]

medchemqs

test your medicinal chemistry knowledge [link]

Alumni

Jordan Bench

Dr. Andrew McGrath

Dr. James L. Douthwaite

Dr. Rui (Sam) Zhang

Dr. Babak (Bo) Mahjour

Dr. Yuning Shen

Dr. Yingfu Lin

Professor at Wuhan University

Dr. Zirong Zhang

Dr. Wenbo Liu

Patents

Timothy A. Cernak, Babak Mahjour, Yuning Shen, Andrew McGrath, Rui Zhang. “Property modulation with chemical transformations”, PCT International Application, 2020, WO2020236314A1.

Kun Liu, Abdelghani Achab, Purakkattle Biju, Timothy A. Cernak, Yongqi Deng, Xavier Fradera, Liangqin Guo, Yongxin Han, Shuwen He, Joseph Kozlowski, Derun Li, Guoqing Li, Qinglin Pu, Zhi-Cai Shi, Wensheng Yu, Hongjun Zhang. “Novel substituted N'-hydroxycarbamimidoyl-1,2,5-oxadiazole compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors”, PCT International Application, 2018, WO2018044663A1.


Dong-Ming Shen, Melissa Egbertson, Richard Berger, Xiaoxia Qian, Yimin Qian, Bart Harper, Meng Yang, Zack Zhi Qiang Guo, Vanessa L. Rada, Deping Wang, Timothy A. Cernak, Christopher J. Sinz, Ming Wang, Jonathan E. Wilson, Shimin Xu. “Pyrimidonecarboxamide compounds as PDE2 inhibitors and their preparation”, PCT International Application, 2015, WO2015096651.


Xiaoqing Han, Alan Whitehead, Subharekha Raghavan, Timothy A. Cernak, Spencer Dreher, Jonathan Groeper, Lian Guo, Yong Zhang. ”Pyrrolopyrimidinone derivatives as soluble guanylate cyclase activators and their preparation”, PCT International Application, 2015, WO2015088886.


Timothy A. Cernak, Kevin D. Dykstra, Dong-Ming Shen, Kun Liu, Andrew Stamford, John Qiang Tan. “Preparation of indazole derivatives as mineralocorticoid receptor antagonists for the treatment of aldosterone-mediated diseases”, PCT International Application, 2014, WO2014014794.


Robert J. DeVita, Shuwen He, Jian Liu, Timothy A. Cernak, Arto D. Krikorian, Ginger Xuqiang Yang, Zhicai Wu; Yang Yu, Dong-Ming Shen, Zhong Lai, Qingmei Hong, Ravi P. Nargund. “Preparation of triazolylpyridine derivatives and analogs for use as DGAT-1 inhibitors”. PCT International Application, 2013, WO201306093.


Timothy A. Cernak, Robert J. DeVita, Yang Yu, Zhicai Wu, Kevin D. Dykstra, Andreas Verras, James M. Balkovec, Alan Whitehead. “Preparation of bicyclo[2.2.2]octane-1-carboxylic acid derivatives as DGAT1 inhibitors for treatment of diabetes and obesity”. PCT International Application 2013, WO2013068328.


Jian Liu, James M. Balkovec, Arto D. Krikorian, Deodial Guiadeen, Ginger Yang, Tianying Jian, Zhicai Wu, Yang Yu, Ravi P. Nargund, Petr Vachal, Robert J. DeVita, Shuwen He, Zhong Lai, Radhika M. Blevis-Bal, Timothy A. Cernak, Donald M. Sperbeck, Qingmei Hong. “Preparation of imidazopyridinzylphenylpyridinylpiperidinylacetic acid derivatives and analogs for use as DGAT1 inhibitors”. PCT International Application 2012, WO2012096813.


Timothy A. Cernak, James M. Balkovec, Ravi P. Nargund, Maud Reiter, Donald M. Sperbeck, Kevin D. Dykstra, Yang Yu, Spencer Dreher, Kevin M. Maloney, Zhicai Wu, Robert J. DeVita, Andreas Verras. “Spirocyclic Compounds for Treatment of Obesity and Diabetes”, PCT International Application 2012, WO2012009217.

admin contact: Caitlin Reynolds cairey@med.umich.edu

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Grow with us! We are looking for graduate students and postdoctoral fellows with an interest in chemical synthesis and data science.

Future graduate students should apply here.

Future postdoctoral fellows should contact Timothy Cernak.

 Images of SPT mosquito ® liquid handling robot from SPT Labtech