cytoskeletal

GFB-8438 is a potent and subtype selective inhibitor of TRPC5(IC50s of 0.18 and 0.29 μM of hTRPC5 and hTRPC4, respectively).

ROCK2-IN-10 is an effective ROCK inhibitor, which is widely used in the research fields of cell migration, invasion, differentiation, proliferation, immune response, drug resistance, cytoskeletal dynamics, etc.

PAIB-SOs-12 is an anti-mitotic compound that shows anti-proliferative activity at low concentrations and induces cytoskeletal damage in MCF7 cells.

Endosidin 7, a specific inhibitor of callose synthase, organizes callose deposition during plant cytoplasmic division without affecting endosomal transport during interphase or cytoskeletal organization, preventing late cytokinesis.

Kinesore is a cell-permeable small molecule modulator that binds primarily to the microtubule motor protein kinesin-1, thereby inhibiting the interaction between KLC2 (kinesin light chain 2) and SKIP (SKIP protein), and thus regulating the structure of the microtubule network to influence cytoskeletal organization and dynamics.

RKI1313 (RKI-1313) was a selective inhibitor for ROCK-dependent signaling, cytoskeletal changes, anchorage-independent colony formation, migration, and invasion.

AA-BR-157 is a PROTAC degrader targeting metallothionein 2A (MT2A) with a DC50 of 190 nM. It downregulates DIAPH3, a protein involved in cytoskeletal and cellular movement regulation, inhibiting cell migration in MDA-MB-231 and U-87 MG cell lines. Additionally, AA-BR-157 modulates zinc homeostasis in MDA-MB-231 cells. (Pink: ligand for target protein MT2A ligand 1; Black: linker; Blue: ligand for VHL E3 ligase).

AK 275 is a calpain inhibitor that prevents degradation of cytoskeletal and myelin proteins in spinal cord in vitro.

Two Rho-associated kinases (ROCK), ROCK-I and ROCK-II, act downstream of the G protein Rho to regulate cytoskeletal stability. The ROCKs play important roles in diverse cellular functions including cell adhesion and proliferation, smooth muscle contraction, and stem cell renewal. Glycyl-H-1152 is a selective and potent ROCK inhibitor (IC50 = 11.8 nM for ROCK-II). It is a glycylated isoquinoline compound derived from the therapeutically-important ROCK inhibitor HA-1077 (Fasudil) and exhibits better specificity. Thus, it poorly inhibits Ca2+/calmodulin-dependent kinase type II, protein kinase (PK) G, and Aurora A (IC50 = 2.57, 2.35, and 3.26 μM, respectively) as well as PKA or PKC (IC50 ≥ 10 μM for each). The potency of Glycyl-H-1152 is superior to that of other ROCK inhibitors, including Y-27632 (Ki = 220 nM) and HA-1077 (IC50 = 158 nM).

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

Protein kinase C (PKC ) is a calcium-independent, phospholipid- and diacylglycerol-dependent serine/threonine kinase involved in diverse signaling pathways, including those involved in neuronal signaling, cytoskeletal function, and inflammation.[1] PKC inhibitor peptide is a synthetic peptide corresponding to an amino acid sequence found in the amino terminal C2 domain of most mammalian forms of PKC .[2] It selectively and reversibly inhibits the translocation of PKC to intracellular membranes, blocking activation.[2] PKC inhibitor peptide is commonly used in cells to evaluate the role of PKC in various cellular responses.[3],[4],[5]

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3, also known as PIP3, is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. PIP3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking. PtdIns-(3,4,5)-P3 (1,2-dihexanoyl) is a synthetic analog of natural PIP3 with C6:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacylglycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog give it different physical properties from naturally-occurring PIP3, including higher solubility in aqueous media.

The phosphatidylinositol phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Centuarin α and the Akt-family of GTPase activating proteins are examples of PtdIns-(3,4,5)-P3-binding proteins. Protein-binding to PtdIns-(3,4,5)-P3 is important for cytoskeletal rearrangements and membrane trafficking. PtdIns-(3,4,5)-P3 is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. For further reading on inositol phospholipids, see also references and .

Sphingosine-1-phosphate (S1P) is a bioactive lipid that exhibits a broad spectrum of biological activities including cell proliferation, survival, migration, cytoskeletal organization, and morphogenesis. It exerts its activity by binding to five distinct G protein-coupled receptors, S1P1/EDG-1, S1P2/EDG-5, S1P3/EDG-3, S1P4/EDG-6, and S1P5/EDG-8. W140 is an inactive enantiomer of W146, a selective S1P1 antagonist (Ki = 77 nM), that binds to the S1P1 receptor with a Ki of 4.6 μM (2a = W146; 2b = W140 in supplemental material). It exhibits no biological activity in vivo and can therefore serve as an effective control compound for experiments involving W146.

Erianin is a nature product extracted from Dendrobium chrysotoxum, has notable antitumour activity , can cause extensive tumour necrosis, growth delay. Erianin has antiangiogenic action by inhibiting endothelial metabolism in a JNK/SAPK-dependent manner a

PF-3758309 dihydrochloride is a potent, reversible, orally active, ATP-competitive PAK4 inhibitor with a Kd value of 2.7 nM and a Ki value of 18.7 nM. PF-3758309 dihydrochloride exhibits the expected cellular functions of a PAK4 inhibitor, with the ability to inhibit anchorage independent growth, induction of apoptosis, cytoskeletal remodelling and inhibition of proliferation.

VJ115 is a novel chemical entity that inhibits the enzyme ENOX1, a NADH oxidase. Genetic and small molecule inhibition of ENOX1 inhibits endothelial cell tubule formation and tumor-mediated neo-angiogenesis. Inhibition of ENOX1 radiosensitizes tumor vasculature, a consequence of enhanced apoptosis. VJ115 inhibition of ENOX1 can impact expression of proteins involved in cytoskeletal reorganization and support a hypothesis in which ENOX1 activity links elevated cellular NADH concentrations with cytoskeletal reorganization and angiogenesis.

Benzo-resolvin D1 (benzo-RvD1), a derivative of the specialized pro-resolving mediator (SPM) RvD1, effectively reduces PDGF-BB-induced cytoskeletal alterations and PDGF-triggered migration in isolated human vascular smooth muscle cells (VSMCs) at 10 and 100 nM concentrations. Additionally, at a 10 nM concentration, benzo-RvD1 inhibits p65 nuclear translocation in human umbilical vein endothelial cells (HUVECs) and enhances phagocytosis of S. aureus and zymosan particles by RAW 264.7 cells.

Sphingosine-1-phosphate (S1P), a bioactive lipid crucial in numerous signaling pathways, undergoes irreversible degradation by membrane-bound S1P lyase, producing (E)-2-Hexadecenal, a derivative of sphingolipid breakdown. This compound can be oxidized to (2E)-hexadecenoic acid by long-chain fatty aldehyde dehydrogenase before being activated through linkage to coenzyme A. Notably, (E)-2-Hexadecenal induces cytoskeletal reorganization, leading to cell rounding, detachment, activation of JNK pathway targets, and ultimate apoptosis in a variety of cell types. Furthermore, it readily forms aldehyde-derived DNA adducts through reactions with deoxyguanosine and DNA.

"(E)-2-Hexadecenal alkyne is a click chemistry probe derivative of the sphingolipid degradation product (E)-2-hexadecenal. This compound has demonstrated the ability to induce cytoskeletal reorganization, leading to cell rounding, detachment, activation of downstream JNK targets, and apoptosis in various cell types. Furthermore, it readily reacts with deoxyguanosine and DNA, forming aldehyde-derived DNA adducts."

Nocarnickelamides B (Compound 2) is a linear peptide and an inhibitor of ROCK1/2. It exhibits dual inhibitory activity against ROCK1 and ROCK2, with IC50 values of 14.9 μM and 21.9 μM, respectively. This compound binds to the ATP binding site and inhibits ROCK-mediated cytoskeletal contraction markers, such as myosin light chain activation. Nocarnickelamides B can be utilized in glaucoma research.