FRAX597

FRAX597 is an inhibitor of p21-activated kinase (PAK) that is selective for group I PAKs (IC₅₀s = 7.7, 12.8, and 19.3 nM for PAK 1, 2, and 3, respectively) over group II PAKs (IC₅₀ > 10 µM for PAK4 and <25% inhibition for PAK6 and PAK7).¹ At 100 nM, it also inhibits YES1, RET, SCR1R, and TEK. FRAX597 reduces phosphorylation of PAK1 (IC₅₀ = 70 nM), prevents proliferation of transformed Schwann cells by halting the cell cycle in the G₁ phase, and reduces the growth of schwannoma mouse xenografts. It also reduces proliferation and survival in ovarian and pancreatic cancer cells and works synergistically with gemcitabine (Item No. 11690) in pancreatic cancer models in vitro and in vivo.^2,3,4

WARNING This product is not for human or veterinary use.

1. Licciulli, S., Maksimoska, J., Zhou, C., et al. FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. The Journal of Biological Chemisty 288(40), 29105-29114 (2013).

2. Yeo, D., He, H., Patel, O., et al. FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine. BMC Cancer 16, 24 (2016).

3. Prudnikova, T.Y., Villmar-Cruz, O., Rawat, S.J., et al. Effects of p21-activated kinase 1 inhibition on 11q13-amplified ovarian cancer cells. Oncogene 35(17), 2178-2185 (2016).

4. Yeo, D., Phillips, P., Baldwin, G.S., et al. Inhibition of group 1 p21-activated kinases suppresses pancreatic stellate cell activation and increases survival of mice with pancreatic cancer. Int. J. Cancer 140(9), 2101-2111 (2017).

Ogura, M., Endo, K., Suzuki, T., et al. Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway. PLoS One 16(2), e0246630 (2021).