New Drugs

We are currently exploring new drugs through:

1. Collaboration with companies
2. Collaboration with academic investigators
3. Screening by high throughput techniques


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


Tsai, Lee et al.
A. PLX4032 in mutant tumors
B. PLX4032 in BRAF wild-type cells



Related 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

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

Lee, J., Li, L., Brafford, P., Sproesser, K., Haass, N., Smalley, K., van den Eijnden, M., Halloran, M., Tsai, J., Bollag, G., Herlyn, M: PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibitrs V600E-positive melanomas. Pigment Cell Melanoma Res. 23, 820-827, 2010. PMID20973932

Feng, Y., Barile, E., De, S.K., Stebbins, J.L., Cortez, A., Aza-Blanc, P., Villanueva, J., Herlyn [Heryln], M., Krajewski, S., Melecchia, M., Ronai, Z.A., Chiang, G.G.: Effective inhibition of melanoma by BI-69A11 is mediated by dual targeting of the AKT and NF-kB pathways. Pigm. Cell Mel. Res. 24: 703-713, 2011. PMID21592316

Blanck, S., Cruchter, T., Vultur, A., Riedel, R., Harms, K., Herlyn, M., Meggers, E.: Organometallic pyridylnaphtalamide complexes as protein kinase inhibitors. Organometallics 30: 4598-4606, 2011. PMID21918590.