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Medicinal Chemistry Knowledge Center

The goal of the Stanford ChEM-H Medicinal Chemistry Knowledge Center is simple - to help biologists and clinicians at Stanford to incorporate medicinal chemistry into their ongoing and future research endeavors.

Protein Bound to Small Molecule

The Stanford ChEM-H Medicinal Chemistry Knowledge Center is led by Dr. Mark Smith, Ph.D., formerly a senior research scientist at Roche Pharmaceuticals. Interested faculty are encouraged to take advantage of Dr. Smith's presence at Stanford to benefit their research programs.

The Stanford ChEM-H MCKC is located on the ground floor of the new Stanford CHEM-H building. It consists of ~1,000 sq feet of laboratory space, consisting of 10 fume hoods of which 7 are fully equipped for synthetic chemistry and 3 support purification and synthesis equipment.. Major equipment consists of a Agilent analytical LCMS, Agilent Semi-prep HPLC, a Biotage microwave reactor, 4 Biotage Selekt automated flash chromatography instruments and a Biotage V10-Touch rapid evaporation system. In vitro ADME assays are performed within the Knowledge Center and In vivo work is conducted in close collaboration with either Stanford core service centers or at local contract research organizations. The Medicinal Chemistry Knowledge Center has access to state of the art informatics infrastructure that includes the Dotmatics drug discovery platform for data capture, query and visualization and Schrodinger’s Maestro platform.

Recent Publications

Structure-Aided Development of Small-Molecule Inhibitors of ENPP1, the Extracellular Phosphodiesterase of the Immunotransmitter cGAMP J. A. Carozza, J.A. Brown, V. Böhnert, D. Fernandez, Y. AlSaif, R.E. Mardjuki G. Skariah, M. Smith and L. Li. Cell Chemical Biology2020, 27, 1-12.

Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity J. A. Carozza, V. Böhnert, K. C. Nguyen, G. Skariah, K. E. Shaw, J. A. Brown, M. Rafat, R. v Eyben, E. E. Graves, J. S. Glenn, M. Smith and L. Li. Nature Cancer2020, 1, 184.

PI4KIII is a therapeutic target in chromosome 1q amplified lung adenocarcinomaX. Tan, P. Banerjee, E. A. Pham, F. U. N. Rutaganira, K. Basu, N. Bota-Rabassedas, H-Fu Guo, C. L. Grzeskowiak, X. Liu, J. Yu, L. Shi, D. H. Peng, B. L. Rodriguez, J. Zhang, V. Zheng, D. Y. Duose, L. M. Solis, B. Mino, M. G. Raso, C. Behrens, I. I. Wistuba, K. L. Scott, M. Smith, K. Nguyen, G. Lam, I. Choong, A. Mazumdar, J. L. Hill, D. L. Gibbons, P. H. Brown, W. K. Russell, K. Shokat, C. J. Creighton, J. S. Glenn, J. M. Kurie. Science Translational Medicine, 2020,12, eaax3772.

Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization, P.A. Allegretti, T.M. Horton, Y. Absolazimi, H.P. Moeller, B. Yeh, M. Caffet, G. Michel, M. Smith, J.P. Annes. Bioorganic and Medicinal Chemistry, 2019, 28, 115193.

SAR optimization studies on modified salicylamides as a potential treatment for acute myeloid leukemia through inhibition of the CREB pathway, H. Chae, N. Cox, S. Capolicchio, J.W. Lee, N. Horikoshi, S. Kam, A.A. Ng, J. Edwards, T. Butler, J. Chan, Y. Lee, G. Potter, M.C. Capece, C.W. Liu, S. Wakatsuki, M. Smith, K.M. Sakamoto. Bioorganic and Medicinal Letters, 2019, 29, 2307-2315.

Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells, T.M. Horton, P.A. Allegretti, S. Lee, H.P Moeller, M. Smith, J.P. Annes. Cell Chemical Biology, 2018, 26.

CC-401 Promotes β-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition, Y. Abdolazimi, Z. Zhao, S. Lee, H. Xu, P. Allegretti, T.M. Horton, B. Yeh, H.P. Moeller, R.J. Nichols, D. McCutcheon, A. Shalizi, M. Smith, N.A. Armstrong, J.P. Annes. Endocrinology, 2018, 159, 3143-3257.

A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection, A. Jacobson, L. Lam, M. Rajendram, F. Tamburini, J. Honeycutt, T. Pham, W.Van Treuren, K. Pruss, S. R. Stabler, K. Lugo, D.M. Bouley, J. G. Vilches-Moure, M. Smith, J.L. Sonnenburg, A.S. Bhatt, K.C. Huang, D. Monack. Cell Host and Microbe, 2018, 24, 296-307.

Niclosamide suppresses acute myeloid leukemia cell proliferation through inhibition of CREB-dependent signaling pathways, H.D. Chae, N. Cox, G.V. Dahl, N.J. Lacayo, K.L. Davis, S. Capolicchio, M. Smith and K.M. Sakamoto. Oncotarget, 2018, 9:4301-4317.

Integrin-Targeting Knotting Peptide-Drug Conjugates Are Potent Inhibitors of Tumor Cell Proliferation, N. Cox, J. Kintzing, M. Smith, G. Grant and J. R. Cochran. Angew. Chem. Int Ed., 2016, 55, 9894.

Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. R. M. Deans, D. W. Morgans, A. Okesli, S. Pillay, M. A. Horlbeck, M. Kampmann, L. A. Gilbert, A. Li, R. Mateo, M. Smith, J. S. Glenn, J. E. Carette, C. Khosla and M. C. Bassik. Nature Chem. Bio. 2016, 12, 361.

Small molecule screen for inhibitors of expression from canonical CREB response element-containing promoters. B. Mitton, K. Hsu, R. Dutta, B.C. Tiu, N. Cox, K.G. McLure, H.D. Chae, M. Smith, E.A. Eklund, D.E. Solow-Cordero, K.M. Sakamoto. Oncotarget. 2016, 7, 8653-62.

*MCKC Members are listed in BOLD

Open Positions

Interested in joining the ChEM-H MCKC?
We are seeking accomplished and motivated Postdoctoral Research Associates with a strong background in synthetic organic chemistry and a desire to work in drug discovery. Successful candidates will work closely with collaborators in existing biomedical research laboratories at Stanford and are expected to play a key role in the advancement of promising small molecule agents into the clinic for the purpose of testing innovative therapeutic hypotheses. The position requires a recent graduate with a Ph.D. in organic chemistry who is experienced with a wide range of synthetic reactions and competent with modern spectroscopic methods applied to structure determination including 1H and 13C NMR and mass spectrometry. Experience with modern purification technology is essential.

 

Applications should be sent to Dr. Mark Smith (mxsmith@stanford.edu) and include a resume, research abstract and contact information for two referees.