Do PAKs make good drug targets?

p21-activated kinases (PAKs) act downstream of Rho-family GTPase and are linked to steps in both cancer initiation and progression. There are six mammalian PAK isoforms that are divided into two groups, and for different reasons both groups are attractive targets for cancer therapy. We describe the background and recent development of a PAK inhibitor, PF-3758309, which exhibits relatively good selectivity and high potency for PAKs. Experiments using PF-3758309 confirm that inhibiting PAK is a beneficial strategy to combat some tumors, and this activity is likely related to modulation of both cell proliferation and survival. The genetic loss of NF2 (neurofibromatosis type 2) leading to increased cell proliferation through a Ras-Rac-PAK pathway may represent a good test system to analyze this new PAK inhibitor

A New Species of \u3cem\u3eDiscinites\u3c/em\u3e (Noeggerathiales) Associated with a New Species of \u3cem\u3eYuania\u3c/em\u3e from the Lower Permian of Inner Mongolia, China

A fructification Discinites baculiformis sp. nov. and the foliage Yuania wudensis sp. nov. are described from the lower Permian Shanxi Formation of Wuda, Inner Mongolia, North China. Discinites baculiformis sp. nov. is at least 31 cm long and 1.5–1.8 cm wide. It has more than 78 whorls of sporophylls, each with ca. 85 sporangia on the adaxial side, a total of more than 6630 sporangia. The impression of the sporophyll epidermis is preserved, and cells are visible. In situ trilete spores are detected. The new species represents the longest strobilus with the largest number of whorls of sporophyll disks so far known in the genus. Yuania wudensis sp. nov. has unbranched rachises, with alternate to subopposite elongate ellipsoidal pinnae. Epidermal cells are rectangular, long, and narrow. The two new species might represent the fructification and foliage of the same parent plant, since there is no other noeggerathialean member in the taphonomic plant community. The association is comparable with the association of Discinites and Russellites from the Permian of Texas