1-naphthyl-pp1-1-na-pp1-hcl

Description: 1-Naphthyl PP1 HCl (also known as 1-NA-PP1 hydrochloride) is a novel, potent and selective ATP-competitive inhibitor of src family kinases v-Src and c-Fyn as well as the tyrosine kinase c-Abl with IC50 values of 1.0, 0.6, 0.6, 18 and 22 uM for v-Src, c-Fyn, c-Abl, CDK2 and CAMK II respectively. Analysis of several related kinases indicated that 1-NA-PP1 was highly selective for PKD as compared to IKK-16. SAR analysis showed that 1-NA-PP1 was considerably more potent and showed distinct substituent effects at the pyrazolopyrimidine core. 1-NA-PP1 was cell-active, and potently blocked prostate cancer cell proliferation by inducing G2/M arrest. It also potently blocked the migration and invasion of prostate cancer cells, demonstrating promising anticancer activities on multiple fronts. Overexpression of PKD1 or PKD3 almost completely reversed the growth arrest and the inhibition of tumor cell invasion caused by 1-NA-PP1, indicating that its anti-proliferative and anti-invasive activities were mediated through the inhibition of PKD. Interestingly, a 12-fold increase in sensitivity to 1-NA-PP1 could be achieved by engineering a gatekeeper mutation in the active site of PKD1, suggesting that 1-NA-PP1 could be paired with the analog-sensitive PKD1(M659G) for dissecting PKD-specific functions and signaling pathways in various biological systems.

References: PLoS One. 2013 Sep 23; 8(9):e75601.; Nature. 2000 Sep 21; 407(6802):395-401.

Related CAS#:221243-82-9 (free base)