PAK4 Inhibitor

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.

Padnarsertib (KPT-9274) is an orally bioavailable, dual PAK4/Nicotinamide phosphoribosyltransferase (Nampt) inhibitor, with IC₅₀s of <100 nM and 120 nM, 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.

LCH-7749944 (GNF-PF-2356) is a potent PAK4 inhibitor with an IC₅₀ of 14.93 μM. LCH-7749944 effectively suppresses the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclin D1 pathway and induces apoptosis.

PAK4-IN-2 is a highly potent PAK4 inhibitor with IC₅₀ value of 2.7 nM. PAK4-IN-2 can arrest MV4-11 cells at G0/G1 phase and induce cell apoptosis. PAK4-IN-2 can be used for researching cancer.

SPU-106 is a p21 activated kinase 4 (PAK4) inhibitor with a target IC₅₀ of 21.36 μM. SPU-106 selectively binds to the C-terminal kinase domain of PAK4 to inhibit its kinase activity. SPU-106 inhibits the PAK4/LIMK1/cofilin and PAK4/SCG10 signaling pathways. SPU-106 inhibits invasion of gastric cancer cells and lacks cytotoxicity against cancer cells. SPU-106 can be used for the research of gastric cancer.

GR2-128 is a dual inhibitor targeting MLK3 and NAMPT with IC₅₀ values of 84 nM and 14 nM, respectively. GR2-128 inhibits downstream JNK/c‑Jun signaling and reduces NAD⁺ levels. GR2-128 exhibits antiproliferative and pro-apoptotic activities in triple-negative breast cancer cells without significant toxicity to normal cells. GR2-128 suppresses tumor growth, reduces macrophage and neutrophil infiltration, and increases tumor T-cell markers in a syngeneic mouse model, and can be used for triple-negative breast cancer research.

CZh226 hydrochloride is a potent and selective PAK4 inhibitor with an IC₅₀ of 18 nM, and its selectivity for PAK1 is 346 times. The oral bioavailability of CZh226 hydrochloride is poor, and it requires the use of the prodrug PAK4-IN-1 (HY-130628) to improve absorption and metabolic stability. CZh226 hydrochloride can be used for research on colorectal cancer and melanoma.

Globulol is a terpenoid metabolite and Antimicrobial agent. Globulol can be isolated from Alpinia oxyphylla Miq. Globulol binds to PAK4, reduces the expression level of PAK4 in cancer cells, decreases the phosphorylation of AKT, and downregulates the expressions of STAT3, phosphorylated STAT3, and PD-L1. Globulol promotes the secretion of CCL4 by cancer cells. Globulol reduces the viability and proliferation ability of cancer cells, induces G0/G1 cell cycle arrest and Apoptosis in cancer cells, and inhibits cancer cell migration and the integrity of 3D tumor spheres. Globulol enhances the relevant effects of anti-PD-1 agents in the cancer cell microenvironment. Globulol exhibits anticancer activity against liver cancer. Globulol inhibits the mycelial growth of phytopathogenic fungi and the growth of phytopathogenic bacteria. Globulol can be used in studies related to hepatocellular carcinoma.

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.

PAK4-IN-1 (Compound 19) is a potent, selective, orally active PAK4 inhibitor with robust anti-tumor efficacy in vivo. PAK4-IN-1 is stable under both acidic and neutral conditions.

PAK4-IN-7 is a selective ATP-competitive inhibitor of p21-activated kinase 4 (PAK4), with an IC₅₀ of 1.88 μM. PAK4-IN-7 inhibits the proliferation of cancer cells. PAK4-IN-7 is applicable for research on tumors such as colorectal cancer and lung cancer.

CZh226 is a selective PAK4 inhibitor with an IC₅₀ of 0.0111 μM and a K_i of 0.009 μM. CZh226 functionally inhibits PAK4 activity and reduces the phosphorylation level of downstream signaling molecules. CZh226 inhibits the migration and invasion of tumor cells. CZh226 is applicable to lung cancer-related research.

KY-04045 is a PAK4 specific inhibitor (IC₅₀=8.7 μM) that can be used for the development of anticancer drugs targeting PAK4.