Therapy: New drugs

We are currently exploring new drugs through:

• Collaboration with companies
• Collaboration with academic investigators
• Screening by high throughput techniques.

This inhibitor is highly specific for BRAF with 10fold higher activity for the mutation than wild-type BRAF.

References

• Tsai, J., Lee, J.T., Wang, W. Zhang, J., Cho, H., Mamo, S., Bremer, R., Gilette, S., Kong, J., Haass, N.K., Sproesser, K., Li, L., Smalley, K.S.M., Fong, D., Zhu, Y-L., Marimuthu, A., Nguyen, H., Lam, B., Liu, J., Cheung, I., Rice, J., Suzuki, Y., Liu, C., Settachatgul, C., Shellooe, R., Cantwell, J., Kim, S-H, Schlessinger, J., Zhang, K.Y.J., West, B., Powell, B., Habets, G., Zhang, C., Ibrahim, P.N. Hirth, P., Artis, D.R., Herlyn, M., Bollag, G.: Discovery of a novel selective inhibitor of oncogenic B-Raf kinase with potent anti-melanoma activity. Proc. Nat. Acad. Sc. (USA) 26: 3041-3049, 2008. PMID18287029
  
  
• Haass, N.K., Sproesser, K., Nguyen, T.K., Contractor, R., Medina, C. A., Nathanson, K. L., Herlyn, M., Smalley, K. S. M.: The MEK inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin. Cancer Res. 14: 230-239, 2008. PMID18172275
  
  
• Xie, P., Williams, D.S., Atilla Gokumen, G.E., Milk, L., Xiao, M., Smalley, K.S., Herlyn, M., Meggers, E., Marmorstein, R.: Structure-based design of an organoruthenium phosphotidyl-inositol-3-kinase inhibitor revieals a switch governing lipid kinase potency and selectivity. ACS Chem. Biol. 3: 305-316, 2008. PMID18484710
  
  
• Maksimoska, J., Williams, D.S., Atilla-Gokcumen, G.E., Smalley, K.S.M., Carroll, P. J., Webster, R. D., Filippakopoulos, P., Knapp, S., Herlyn, M., Meggers, E.: Isostructural ruthenium and osmium complexes display highly similar bioactivities. Chemistry 14: 4816-4822, 2008. PMID18425743
  
  
• King, A.J., Patrick, D.R., Batorsky, R.S., Ho, M.L., Do, H.T., Zhang, S-Y., Kumar, R., Rusnak, D.W., Takle, A.K., Wilson, D.M., Hugger, E., Wang, L., Karreth, F., Lougheed, J.C., Lee, J., Chau, D., Stout, T.J., May, E.W., Rominger, C.M., Schaber, M.D., Luo, L., Lakdawala, A.S., Adams, J.L., Contractor, R.G., Smalley, K.A.M., Herlyn, M., Morrissey, M.M., Tuveson, D.A., Huang, P.S.: Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 66: 11100-11105, 2006. PMID 17145850
  
  
• Smalley, K.S.M., Contractor, R., Haass, N.K., Kulp, A. N., Atilla-Gokcumen, G.E., Williams, D.S., Bregman, H., Flaherty, K.T., Soengas, M.S., Meggers, E., Herlyn, M.: A organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells. Cancer Res. 67: 209-217, 2007. PMID 17210701