FAK Inhibitor

PF-562271 hydrochloride (VS-6062 hydrochloride) is an orally active, ATP-competitive, reversible FAK/Pyk2 inhibitor, with an IC₅₀ of 1.5 nM for FAK and 13 nM for Pyk2. PF-562271 hydrochloride induces tumor regression, and inhibits tumor growth, invasion and metastasis. PF-562271 hydrochloride exerts no effect on tumor necrosis, angiogenesis or apoptosis in an orthotopic mouse model of pancreatic ductal adenocarcinoma. When combined with Sunitinib (HY-10255A), PF-562271 hydrochloride reduces tumor vascularization, decreases serum alpha-fetoprotein levels and improves cachexia. PF-562271 hydrochloride can be used in research related to prostate cancer, breast cancer, pancreatic cancer, colon cancer, glioblastoma, lung cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma.

FAK ligand-2 is a FAK ligand and a ligand for the target protein of PROTAC (FAK). FAK ligand-2 can be used to synthesize BSJ-04-146 (HY-179512).

ALK inhibitor 1 (compound 17) is a potent pyrimidin ALK inhibitor. ALK inhibitor 1 is a potent inhibitor of testis-specific serine/threonine kinase 2 (TSSK2; IC₅₀=31 nM) and focal adhesion kinase (FAK; IC₅₀=2 nM).

(Rac)-AAA is a regulator and inhibitor targeting GPR75. By blocking the 20-HETE-induced downregulation of GPR75 expression, (Rac)-AAA effectively inhibits the activation of key downstream signaling pathways including EGFR, AKT, NF-κB and FAK. (Rac)-AAA reverses 20-HETE-mediated epithelial-mesenchymal transition, which is specifically characterized by downregulating vimentin (vimentin), upregulating E-Cadherin, as well as reducing MMP-2 activity and cancer cell migration ability. (Rac)-AAA also abolishes the 20-HETE-induced upregulation of HIC-5 expression and anchorage-independent growth, and modulates the subcellular localization of PKC-α and phosphorylated AKT. (Rac)-AAA is investigated in androgen-independent prostate cancer (castration-resistant prostate cancer).

FAK-IN-20 (Compound 7b) is an inhibitor of FAK with an IC₅₀ value of 0.27 nM. FAK-IN-20 exhibits anticancer activity. FAK-IN-20 can arrest the cell cycle in the G2/M phase and induce cell apoptosis by generating ROS.

FAK-IN-23 (Compound II) is the inhibitor for focal adhesion kinase (FAK).

PHM16 is an ATP competitive inhibitor of FAK and FGFR2 (IC₅₀: 0.4 μM and 0.37 μM, respectively), with direct potent anti-angiogenic activity.

EGFR T790M/FAK-IN-1 is a dual inhibitor of EGFR^T790M and FAK, with an IC₅₀ of 99.1 nM against EGFR^T790M and an IC₅₀ of 117.7 nM against FAK. EGFR T790M/FAK-IN-1 can be used for research on pancreatic cancer, drug-resistant breast cancer, and drug-resistant lung cancer.

FAK-IN-15 (Compound 9b) is a focal adhesion kinase (FAK) inhibitor with an IC₅₀ value of 0.2691 nM. FAK-IN-15 has anti-tumor activity with an IC₅₀ value of 1.033 μM against U87-MG cells.

FNIII14 is a β1-integrin inhibitory peptide. FNIII14 induces the conformational shift of β1-integrin from the active form to the inactive form, blocks integrin-mediated signaling pathways, disrupts the interaction between VLA-4 and fibronectin, inhibits the phosphorylation of FAK/Akt, suppresses cell adhesion, fibronectin fibril formation and chondrocyte proliferation, induces chondrocyte apoptosis and cartilage degeneration, upregulates the pro-apoptotic protein Bim, and binds to membrane-bound eEF1A. FNIII14 reversibly disrupts cell adhesion without reducing cell viability, accelerates adipocyte differentiation, and loosens tumor matrix architecture to enhance the permeability of nanotherapeutic agents. FNIII14 can be used in research related to neuroblastoma, pancreatic cancer, acute myeloid leukemia, colitis-associated colorectal cancer, osteoarthritis, and atherosclerosis.

PH11 is a novel focal adhesion kinase (FAK) inhibitor that rapidly induces apoptosis in TRAIL-resistant PANC-1 cells when combined with TRAIL, but has no effect on normal human fibroblasts. The study found that PH11 downregulates c-FLIP through inhibition of FAK and phosphatidylinositol-3-kinase (PI3K)/AKT pathways, thereby restoring the TRAIL apoptotic pathway, suggesting that this combination therapy may provide an attractive therapeutic strategy for the safe and effective treatment of pancreatic cancer. PH11 selectively inhibits c-FLIP expression by modulating upstream signaling pathways and may represent an innovative therapeutic strategy. Although further work is needed to fully elucidate the mechanism of PH11-induced TRAIL sensitization, we believe that our results will provide a new approach to target c-FLIP without the risk of interfering with caspase-8 processing, which could potentially lead to TRAIL resistance. This study also suggests a role for the FAK/AKT signaling pathway in regulating c-FLIP expression in TRAIL-induced apoptosis, and this understanding will provide important clues to control the resistance mechanism to optimize the potential of TRAIL-based pancreatic cancer treatment.

FAK-IN-25 (4c) is a FAK inhibitor with an IC₅₀ of 50.98 nM. FAK-IN-25 (4c) induces apoptosis and causes cell cycle arrest at G1 phase. FAK-IN-25 (4c) can be used in cancer research.

FAK-IN-32 is an orally active, selective and highly potent FAK inhibitor (IC₅₀ = 10.87 nM). FAK-IN-32 can induce cell cycle arrest at the G2/M phase, inhibit FAK-AKT signaling pathway activity, and promote apoptosis to some extent. FAK-IN-32 can be used for research on KRAS-mutant colorectal cancer.

FAK-IN-30 is a focal adhesion kinase (FAK) inhibitor with moderate cytotoxicity against breast cancer cells. FAK-IN-30 can be used for the research of triple-negative breast cancer.

SPP-037 is an orally active and selective inhibitor of ST6GAL1 (IC₅₀ = 3.59 μM). SPP-037 inhibits integrin α2,6-sialylation and integrin-FAK-paxillin pathway. SPP-037 inhibits cancer cell proliferation, migration and exhibits antiangiogenic activity. SPP-037 has anti-tumor activity in MDA-MB-231 xenograft mouse model. SPP-037 can be used for the research of triple-negative breast cancer.

FAK-IN-5 (Compound 8l) is a FAK signaling inhibitor. FAK-IN-5 induces cell apoptosis and autophagy.

ALK-IN-29 (compound 4c) has a certain inhibitory effect on tyrosine protein kinases ALK, CDK2/CyclinE1 and FAK, among which the strongest inhibitory effect on ALK kinase is 40.63% at a concentration of 10 μM. ALK-IN-29 can be used for anti-cancer research.

EGFR-IN-46 is a potent EGFR and FAK dual inhibitor with IC₅₀s of 20.17 nM, 14.25 nM, respectively. EGFR-IN-46 significantly inhibits the growth of cancer cells. EGFR-IN-46 induces cell apoptosis.

FAK-IN-22 (Compound 26) is an inhibitor of FAK, JAK3, and Aurora B, with IC₅₀ values of 50.94 nM, 9.99 nM, and 0.49 nM, respectively, effectively inhibiting tumor occurrence and metastasis in pancreatic ductal adenocarcinoma (PDAC). FAK-IN-22 effectively inhibits the proliferation of PANC-1 cells, with an IC₅₀ value of 0.15 μM. FAK-IN-22 induces apoptosis and G2/M phase arrest in PANC-1 cells by inhibiting the FAK/PI3K/Akt signaling pathway.

GZD-552 is a potent orally active FAK inhibitor with a human FAK IC₅₀ of 5.8 nM. GZD-552 suppresses FAK phosphorylation activation and downstream ERK signaling. GZD-552 induces apoptosis and G₂/M cell cycle arrest, and exhibits antiproliferative activities in glioblastoma multiforme cells. GZD-552 exhibits antitumor efficacy in mice xenograft model. GZD-552 can be used for the research of glioblastoma multiforme.