A potent and selective inhibitor of FAK phosphorylation with biochemical IC50 of 1.2 pM (pFAK Y397), cellular IC50 of 1 nM; displays 8-fold selectivity over PYK2, 26-fold selectivity over RSK1/2 , and >1000-fold selectivity over SRC, AURKA, AURKB, INSR, and KDR; suppresses pFAK Y397 and pFAK Y861 in tumors and liver, shows tumor growth inhibition in TOV21G xenografts in mice.
Petunidin chloride is an O-methylated anthocyanidin derived from delphinidin that imparts blue-red pigments to flowers, fruits, and red wine. Petunidin chloride binds with and suppresses the activity of focal adhesion kinase and to inhibit platelet-derived growth factor-induced aortic smooth muscle cell migration, which may confer a protective effect against atherosclerosis.
PDZ1i (113B7) is a specific inhibitor of MDA-9/Syntenin activity that inhibits MDA-9/Syntenin binding to EGFRvIII; selectively binds with micromolar affinity to the PDZ1 domain of MDA-9/Syntenin, with no affinity for PDZ2 domain of MDA-9/Syntenin; reduces invasion gains in GBM cells following radiation, inhibits crucial GBM signaling involving FAK and mutant EGFR, EGFRvIII, and abrogated gains in secreted proteases, MMP-2 and MMP-9, following radiation; results in smaller, less invasive tumors and enhanced survival in an in vivo glioma model.
FLT3-IN-17 inhibits CYPs and FLT3 mutants activity (IC50s: <0.5 nM for D835Y). FLT3-IN-17 is also a FAK inhibitor, with an IC50 value of 12 nM. FLT3 ligand-2 can be used in the research of cancers[1].
Fangchinoline is isolated from Stephania tetrandra with extensive biological activities, such as enhancing immunity, anti-inflammatory sterilization and anti-atherosclerosis. Fangchinoline, a novel HIV-1 inhibitor, inhibits HIV-1 replication by impairing gp160 proteolytic processing[1]. Fangchinoline targets Focal adhesion kinase (FAK) and suppresses FAK-mediated signaling pathway in tumor cells which highly expressed FAK[2]. Fangchinoline induces apoptosis and adaptive autophagy in bladder cancer[3].
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[1].
AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].
FAK inhibitor 5 (compound 2) is a novel allosteric FAK inhibitor, with IC50 values in the low micromolar range[1].
PROTAC FAK degrader 1 is a selective and potent focal adhesion kinase (Fak) degrader with an IC50 of 6.5 nM, DC50 of 3 nM[1].
PF-573228 is a potent and selective FAK inhibitor with IC50 of 4 nM for purified recombinant catalytic fragment of FAK.
Batatasin III, a stilbenoid, inhibits cancer migration and invasion by suppressing epithelial to mesenchymal transition (EMT) and FAK-AKT Signals. Batatasin III has anti-cancer activities[1].
BI 853520 (IN-10018) is an orally active and potent focal adhesion kinase (FAK) inhibitor (recombinant FAK IC50=1 nM). BI 853520 shows anti-proliferative activity against cancer cells[1][2].
FAK PROTAC B5 (Compound B5) is a FAK PROTAC degrader with an IC50 value of 14.9 nM. FAK PROTAC B5 presents strong FAK degradation activity, antiproliferative activity, outstanding plasma stability and moderate membrane permeability. FAK PROTAC B5 inhibits cell migration and invasion[1].
GSK2256098 is a selective FAK kinase inhibitor, which inhibits growth and survival of pancreatic ductal adenocarcinoma cells.
FC-11 is a PROTAC FAK degrader (DC90: 1 nM) . FC-11 contains CRBN ligand Pomalidomide (HY-10984), linker and FAK ligand PF562271 (HY-10459). FC-11 degrades FAK in various cells, with DC50s of 310 pM in TM3, 80 pM in PA1, 330 pM in MDA-MB-436, 370 pM in LNCaP, and 40 pM in Ramos cells[1].
ULK1-IN-2 (compound 3s) is a potent ULK1 inhibitor. ULK1-IN-2 shows highest cytotoxic effect against cancer cell lines, with IC50 of 1.94 μM in A549. ULK1-IN-2 can induce apoptosis and simultaneously block autophagy, and can be used to study NSCLC (Non-small cell lung cancer)[1].
FAK-IN-7 (compound 5r) is a FAK inhibitor (IC50=11.72 µM). FAK-IN-7 has good anti-proliferative activity and can be used in cancer research[1].
FAK-IN-10 is an inhibitor of FAK with an IC50 of 76.3 μM. FAK-IN-10 exhibits antitumor activity against MCF-7 and A431 cell lines with IC50s of 4.23 and 0.78 μM,respectively[1].
Chloropyramine hydrochloride is a histamine receptor H1 antagonist which can also inhibit the biochemical function of VEGFR-3 and FAK.
YH-306 is a candidate drug in preventing growth and metastasis of colorectal cancer by modulating FAK signalling pathway.
Defactinib hydrochloride is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.
BI-4464 is a highly selective ATP competitive inhibitor of PTK2/FAK, with an IC50 of 17 nM. A PTK2 ligand for PROTAC[1].
Novel FAK activator, promoting human intestinal epithelial monolayer wound closure and mouse ulcer healing
Adhesamine, dumbbell-shaped molecule, activates MAPK/FAK pathway. Adhesamine promotes adhesion and growth of mammalian cells. Adhesamine accelerates the differentiation and improves the survival of mice hippocampal neurons in primary culture[1].
PF-562271 (besylate) is a potent, ATP-competitive, reversible inhibitor of FAK and Pyk2 kinase with IC50 of 1.5 nM and 13 nM, and has > 100-fold selectivity against other protein kinases, except for some CDKs.
APG-2449 is an orally active ALK/ROS1/FAK inhibitor. APG-2449 shows antitumor activity in mouse models of non-small cell lung cancer (NSCLC)[1].
NVP-TAE 226 is a dual tyrosine kinase inhibitor of FAK (IC50=5.5 nM) and IGF-IR (mean IC50=0.14 μM).
AMP-945 is an inhibitor of the enzyme focal adhesion kinase (FAK)[1].
Y15 is a direct and specific inhibitor of FAK auto-phosphorylation.
NAMI-A is a ruthenium-based drug characterised by the selective activity against tumour metastases, inhibits the adhesion and migration.In vitro: NAMI-A can significantly affect tumor cells with metastatic ability.The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations. [1] The ruthenium drug NAMI-A inhibits the adhesion and migration of colorectal cancer cells. NAMI-A decreases α5β1 integrin expression and FAK auto-phosphorylation on Tyr 397. [2]In vivo: The reference for NAMI-A is 35 mg/kg/day. [1]