PAK1 Inhibitor

5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB. 5-Aminosalicylic acid can inhibit the activity of osteopontin (OPN).

IPA-3 is a selective non-ATP competitive PAK1 inhibitor with IC₅₀ of 2.5 μM, and shows no inhibition to group II PAKs (PAKs 4-6).

PF-3758309 (PF-03758309) is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (K_d= 2.7 nM; K_i=18.7 nM). PF-3758309 has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation.

SIK2/3-IN-2 (compound 12, compound I-200) is a potent SIK2/3 inhibitor (SIK2 IC₅₀ = 65 nM, SIK3 IC₅₀ = 14 nM). SIK2/3-IN-2 is also a p21-activated protein kinase (PAK) 1 inhibitor with a K_i of 20.7 nM. SIK2/3-IN-2 can be used for hyperproliferative diseases and cancer research, such as Paclitaxel (HY-B0015)-resistant ovarian cancer.

AKT1-IN-13 is an orally active AKT1 inhibitor with an IC₅₀ of 5.17 μM. AKT1-IN-13 also exhibits high inhibitory activity against PAK1, PKA, MAP2K1 (MEK1 / MAPKK1) and MAPK1 (ERK2). AKT1-IN-13 induces cell apoptosis, activates the pro-apoptotic protein BAX, inhibits the anti-apoptotic protein Bcl-2, and activates caspase 3 simultaneously. As a cytotoxic agent, AKT1-IN-13 exerts a killing effect on orthotopically transplanted liver cancer in an AKT1-dependent manner. AKT1-IN-13 can be used in studies related to hepatocellular carcinoma.

PAK1-IN-3 is a PAK1 inhibitor with an IC₅₀ of 10 nM, an IC₅₀ of 20 nM against PAK2, and an IC₅₀ of 1079 nM against hERG potassium channels. PAK1-IN-3 forms a salt bridge with Asp106 in PAK1 via a properly positioned tertiary amine. PAK1-IN-3 inhibits PAK2 and hERG potassium channels.

FRAX597 is a potent group I p21-activated Kinases (PAKs) inhibitor with IC₅₀ of 8, 13 and 19 nM for PAK1, 2 and 3.

FRAX486 is a p21-activated kinase (PAK) inhibitor with IC₅₀s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively.

G-5555 is a potent p21-activated kinase 1 (PAK1) inhibitor with K_is of 3.7 nM and 11 nM for PAK1 and PAK2, respectively.

FRAX1036 is a PAK inhibitor with K_is of 23.3 nM, 72.4 nM, and 2.4 μM for PAK1, PAK2 and PAK4, respectively.

AZ13705339 is a highly potent and selective PAK1 inhibitor with IC₅₀s of 0.33 nM and 59 nM for PAK1 and pPAK1, respectively. AZ13705339 has binding affinities to PAK1 and PAK2, with K_ds of 0.28 nM and 0.32 nM, respectively. AZ13705339 can be used in the research of cancers.

G-5555 hydrochloride is a potent and selective p21-activated kinase 1 (PAK1) inhibitor with a K_i of 3.7 nM.

NVS-PAK1-C is a potent, ATP-competitive and specific allosteric PAK1 inhibitor probe with IC₅₀ values of 5 nM and 6 nM for dephosphorylated PAK1 and phosphorylated PAK1, respectively. NVS-PAK1-C is also against dephosphorylated PAK2 (IC₅₀=270 nM) and phosphorylated PAK2 (IC₅₀=720 nM).

AZ13705339 hemihydrate is a highly potent and selective PAK1 inhibitor with IC₅₀s of 0.33 nM and 59 nM for PAK1 and pPAK1, respectively. AZ13705339 hemihydrate has binding affinities to PAK1 and PAK2, with K_ds of 0.28 nM and 0.32 nM, respectively. AZ13705339 hemihydrate can be used in the research of cancers.

PAK1-IN-1 is a potent and selective PAK1 inhibitor with an IC₅₀ of 9.8 nM. PAK1-IN-1 inhibits the migration and invasion of PAK1-related tumour cells in a dose-dependent manner.

PF-3758309 (PF-03758309) hydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (K_d= 2.7 nM; K_i=18.7 nM). PF-3758309 hydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation.

PAK4-IN-5 (Compound 12i) is a PAK4 inhibitor (IC₅₀: 7.68 nM for PAK4, 1872.01 nM for PAK1). PAK4-IN-5 binds to PAK4 stably via multiple interactions. PAK4-IN-5 inhibits the proliferation and the migratory potential of MDA-MB-231 cells by inhibiting the phosphorylation of PAK4 and LIMK1. PAK4-IN-5 arrests cell cycle in the G0/G1 phase, induces apoptosis and ROS production. LD₅₀: >500 mg/kg for mice (p.o.).

PF-3758309 (PF-03758309) dihydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (K_d= 2.7 nM; K_i=18.7 nM). PF-3758309 dihydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation.

G-9791, a poyridone side chain analogue, is a potent PAK inhibitor with K_i values of 0.95 nM and 2.0 nM for PAK1 and PAK2, respectively.

2,2′-Dihydroxy-6,6′-dinaphthyl disulfide (PIR-3.5) is a PAK1 inhibitor.