Two papers were recently published reporting results obtained in projects carried out in collaboration with Prof. Chaitan Khosla of Stanford University and with Prof. Carl Nathan of Weill Cornell Medical College. This work illustrates our ability to rapidly advance early stage projects to hit-to-lead and lead optimization, even when starting from only a couple dozen, non-diverse active compounds. The work with Prof. Khosla on inhibitors of transglutaminase 2 (TG2) as potential therapies for celiac disease and metastatic cancer has resulted in the identification of multiple new and proprietary lead series. The work with Prof. Nathan on inhibitors of protein kinase R (PKR) as therapies for tuberculosis resulted in the identification of a valuable probe compound, NMRT-2862, which inhibits PKR within macrophages without overt cytotoxicity and recapitulates the effects of genetic inactivation of PKR.
“Acylideneoxoindoles: A new class of reversible inhibitors of human transglutaminase 2.” C. Klöck, X. Jin, K. Choi, C. Khosla, P.B. Madrid, A. Spencer, B.C. Raimundo, P. Boardman, G. Lanza and J.H. Griffin. Bioorg. Med. Chem. Lett. 2011, 21, 2692-2696.
“Identification of new inhibitors of protein kinase R guided by statistical modeling.” R. Bryk, K. Wu, B.C. Raimundo, P.E. Boardman, P. Chao, G.L. Conn, E. Anderson, J.L. Cole, N.P. Duffy, C. Nathan and J.H. Griffin. Bioorg. Med. Chem. Lett. 2011, 21, 4108-4114.