Our technology

Our proprietary approach to activate PP2A

PP2A is a key tumor suppressor and a critical enzyme regulating protein de-phosphorylation and tumor growth, but it has to date been very difficult to target pharmaceutically.

Our approach

Our proprietary approach to activate PP2A

Rappta’s scientific team includes pre-eminent PP2A scientists who have published extensively on PP2A chemistry and biology. Based on our deep understanding of PP2A biology and proprietary tools we have developed compounds that reactivate PP2A and launched a program to develop these compounds into a new class of anti-cancer drugs.

Our small molecule compounds act as a glue to allow for the three subunits of PP2A to bind together driving PP2A complex reformation to target a wide array of oncogenic substrates. By solving a high-resolution structure of PP2A-Drug complex, we have been able to develop an entire new series of compounds to interlock the PP2A subunits and specifically reactivate its tumor suppressive function.

Key articles

Key articles by the members of our team

Leonard, D., Huang, W., Izadmehr, S., O’Connor, C. M., Wiredja, D. D., Wang, Z., Zaware, N., Chen, Y., Schlatzer, D. M., Kiselar, J., Vasireddi, N., Schuchner, S., Perl, A. L., Galsky, M. D., Xu, W., Brautigan, D. L., Ogris, E., Taylor, D. J. & Narla, G. (2020) Selective PP2A Enhancement through Biased Heterotrimer Stabilization, Cell. 181, 688-701 e16.

Sangodkar, J., Perl, A., Tohme, R., Kiselar, J., Kastrinsky, D. B., Zaware, N., Izadmehr, S., Mazhar, S., Wiredja, D. D., O’Connor, C. M., Hoon, D., Dhawan, N. S., Schlatzer, D., Yao, S., Leonard, D., Borczuk, A. C., Gokulrangan, G., Wang, L., Svenson, E., Farrington, C. C., Yuan, E., Avelar, R. A., Stachnik, A., Smith, B., Gidwani, V., Giannini, H. M., McQuaid, D., McClinch, K., Wang, Z., Levine, A. C., Sears, R. C., Chen, E. Y., Duan, Q., Datt, M., Haider, S., Ma’ayan, A., DiFeo, A., Sharma, N., Galsky, M. D., Brautigan, D. L., Ioannou, Y. A., Xu, W., Chance, M. R., Ohlmeyer, M. & Narla, G. (2017) Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth, J Clin Invest. 127, 2081-2090.

Kauko, O., O’Connor, C. M., Kulesskiy, E., Sangodkar, J., Aakula, A., Izadmehr, S., Yetukuri, L., Yadav, B., Padzik, A., Laajala, T. D., Haapaniemi, P., Momeny, M., Varila, T., Ohlmeyer, M., Aittokallio, T., Wennerberg, K., Narla, G. & Westermarck, J. (2018) PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells, Sci Transl Med. 10.

McClinch, K., Avelar, R. A., Callejas, D., Izadmehr, S., Wiredja, D., Perl, A., Sangodkar, J., Kastrinsky, D. B., Schlatzer, D., Cooper, M., Kiselar, J., Stachnik, A., Yao, S., Hoon, D., McQuaid, D., Zaware, N., Gong, Y., Brautigan, D. L., Plymate, S. R., Sprenger, C. C. T., Oh, W. K., Levine, A. C., Kirschenbaum, A., Sfakianos, J. P., Sears, R., DiFeo, A., Ioannou, Y., Ohlmeyer, M., Narla, G. & Galsky, M. D. (2018) Small-Molecule Activators of Protein Phosphatase 2A for the Treatment of Castration-Resistant Prostate Cancer, Cancer Res. 78, 2065-2080.

Farrington, C. C., Yuan, E., Mazhar, S., Izadmehr, S., Hurst, L., Allen-Petersen, B. L., Janghorban, M., Chung, E., Wolczanski, G., Galsky, M., Sears, R., Sangodkar, J. & Narla, G. (2020) Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers, J Biol Chem. 295, 757-770.