Cytoskeletal Signaling

<p>KY-02327 acetate inhibits Dvl-CXXC5, stabilizes Wnt/β-catenin signaling, and enhances osteoblast differentiation.</p>

<p>RMS-07, a covalent MPS1/TTK inhibitor, has an IC50 of 13.1 nM, targeting a kinase hinge cysteine.</p>

<p>SR121566A is a novel non-peptide antagonist of Glycoprotein IIb/IIIa (GP IIb-IIIa).</p>

<p>C086 is a novel and potent Hsp90 inhibitor that suppresses cell cycle progression, induces apoptosis, and exhibits anti-metastatic properties by modulating various mechanisms in different cell types.</p>

<p>6-B345TTQ is an α4 integrin inhibitor that can impede the interaction between α4 and Leupaxin. This compound is applicable for studies focused on inflammation research.</p>

<p>MT-134 is a SkMII -specific inhibitor and has excellent exposure in muscles.</p>

<p>Tau ligand-1 (Compound 75) is a ligand of aggregated tau protein that can penetrate the blood-brain barrier. In tissues affected by Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, and Pick's disease, Tau ligand-1 shows high affinity for aggregated tau protein, with equilibrium dissociation constants (KD) ranging from 1 to 3.8 nM. It holds potential as a positron emission tomography (PET) tracer for imaging studies of tau-related diseases within the central nervous system.</p>

<p>Compound 13m, a difluoro derivative, activates Nrf2/HO-1, showing neuroprotective and antioxidant effects, useful in PD research.</p>

<p>GR 83895 is an antagonist of prototype fibrinogen receptor.</p>

<p>Des-ethyl-carafiban (Compound 44) is an antagonist of the fibrinogen receptor, effectively inhibiting platelet aggregation induced by various agonists. It is useful for research in thrombotic diseases.</p>

<p>POSH-IN-2 (MIDI) is a mitochondrial fission inhibitor and a DRP1 inhibitor that effectively prevents mitochondrial fragmentation caused by cellular stress and genetic mitochondrial damage. It covalently interacts with DRP1-C367 to target the interaction of DRP1 with multiple receptors.</p>

<p>GSK3335103 is a non-peptide, orally active inhibitor of αvβ6 integrin (pIC50=8), employed in the study of pulmonary fibrosis.</p>

<p>FO-4-15 is an activator of mGluR1/CaMKIIα. It exhibits protective effects against H2O2 in human neuroblastoma (SH-SY5Y) cells. In mice with Alzheimer's disease, FO-4-15 enhances cognitive function by activating the mGluR1/CaMKIIα pathway, reducing Aβ accumulation, Tau hyperphosphorylation, and synaptic damage.</p>

<p>NRX-2663 boosts β-catenin binding to E3 ligase SCFβ-TrCP (Kd: 54.8 nM, EC50: 22.9 nM).</p>

<p>Fradafiban binds to the human platelet GP IIb/IIIa complex with a Kd value of 148 nM. Fradafiban is a non-polypeptide platelet glycoprotein IIb/IIIa antagonist.</p>

<p>Row174336 (compound 29) serves as an efficient inhibitor of the Hsp110-STAT3 interaction, exhibiting antiproliferative activity in the HPAEC cell line with an IC50 of 22.67 μM.</p>

<p>Compound IIc inhibits tubulin polymerization, arrests cell cycle at G2/M in HCT116 cells, IC50 12.7 μM, potential for cancer research.</p>

<p>Ack1 inhibitor 1 is a potent and selective orally active inhibitor of ACK1 kinase, with an IC50 value of 2.1 nM. It effectively inhibits the phosphorylation of ACK1 and the activation of downstream AKT, demonstrating anti-tumor activity [1].</p>

<p>TTBK1/2-IN-3 (compound 10) is a potent inhibitor of Tau tubulin kinase 1 (TTBK1) and TTBK2, with IC50 values of 579 nM and 258 nM, respectively. TTBK1/2-IN-3 can reduce the expression of primary cilia on the surface of human induced pluripotent stem cells (iPSC).</p>

<p>ETB is a potent inhibitor of Hsp60 chaperone activity. It can impede the chaperone function of both wild-type proteins and the C237A and C447A mutant proteins. ETB binds to Hsp60 at Cys442, and the C442A mutant demonstrates resistance to ETB inhibition.</p>

<p>KAA, an anticancer compound, inhibits centrosome clustering and targets HSET+ yeast and cancer cells.</p>

<p>Tubulin-IN-33, an oxazoloisoindole, hinders microtubule assembly; effective against NCI cancer cells.</p>

<p>TPI 287: synthetic taxane; may halt cancer by stabilizing microtubules, blocking cell division, inducing apoptosis.</p>

<p>Compound 24: Potent Nrf2/HO-1 activator with neuroprotective, antioxidant properties; useful in PD research.</p>

<p>Tubulin-IN-35 inhibits oxazolylisoindole microtubule formation, targeting VL51 marginal zone lymphoma.</p>

<p>Onalespib lactate is a second-generation, potent and selective HSP90 Inhibitor with antitumor activity.</p>

<p>Antitumor agent-200 (Compound 2g) is a microtubule synthesis inhibitor that binds to the colchicine site on tubulin, causing G2/M cell cycle arrest and inducing reactive oxygen species (ROS) production. It demonstrates significant inhibitory activity against P-glycoprotein (P-gp) overexpressing cell lines MCF7/ADR and KBV200, with resistance indices (DRI) of 0.83 and 0.58, respectively. In an MCF-7 xenograft model, Antitumor agent-200 (at 25 mg/kg, administered intraperitoneally) achieves a 57.2% tumor growth inhibition rate. This compound is applicable for research in the field of cancer therapy.</p>

<p>Tubulin inhibitor 49 (Compound 18) is an inhibitor of tubulin polymerization with an IC50 of 48 μM. It disrupts the microtubule network of cells, causing cell cycle arrest in the G2 phase, and exhibits cytotoxicity with an IC50 of 8.8 μM in HeLa cells.</p>

<p>Quinagolide hydrochloride is a selective agonist of dopamine D2 receptor.</p>

<p>XD23 is a potent osteosarcoma inhibitor that functions by downregulating DKK1 and activating the WNT/β-catenin signaling pathway.</p>

<p>HSP90-IN-9: potent HSP90 inhibitor, dose-dependent fungicide, impedes biofilm/morphology with FLC, reverses FLC resistance.</p>

<p>AChE/GSK-3β-IN-1 is a potent dual AChE/GSK-3β inhibitor that crosses the blood-brain barrier and acts on hAChE (IC50: 1.2 nM), hBChE (IC50: 149.8 nM) and hGSK-</p>

<p>SPA0355 is a thiourea derivative with antioxidant and anti-inflammatory properties. It inhibits RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclastogenesis in primary bone marrow-derived macrophages and suppresses the activation of MAPKs, Akt, and NF-κB pathways. Furthermore, SPA0355 enhances osteoblast differentiation by increasing alkaline phosphatase activity and mineralized nodule formation. It protects ovariectomized mice from bone loss by stimulating osteoblast differentiation and inhibiting osteoclast resorption, making it a potential candidate for studying postmenopausal osteoporosis.</p>

<p>SF0166: potent αvβ3 antagonist, IC50: 0.6 nM. Blocks cell adhesion, IC50: 7.6 pM-76 nM. Reduces neovascularization in mice.</p>

<p>HSN748 is an analog of ponatinib and acts as a multi-kinase inhibitor. It exhibits inhibitory activity against kinases such as FLT3, ABL1, RET, PDGFRα/β, MNK1, and MNK2. HSN748 can suppress the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines, making it a useful compound in leukemia research.</p>

<p>Ethaboxam is a β-tubulin inhibitor and antifungal agent used against oomycete pathogens.</p>

<p>AKT-IN-26 (Compound 453) is an AKT inhibitor that binds to the Pleckstrin Homology (PH) domain of AKT. It is useful for research related to cell proliferation and cancer involving the AKT pathway.</p>

<p>Hsp90-IN-38 (compound 20m) is an inhibitor of HSP90 (heat shock protein). It demonstrates a strong binding affinity to HSP90 with a Kd of 87 nM. The compound inhibits ATPase activity with an IC50 of 0.13 μM. Hsp90-IN-38 also shows inhibitory effects on HCT116, MCF-7, SKBr3, K562, and A549 cells with IC50 values of 0.187, 0.072, 0.105, 0.403, and 0.031 μM, respectively.</p>

<p>NAP1051, a biomimetic analog of Lipoxin A4, serves an anti-tumor role by targeting the inflammatory tumor microenvironment. It inhibits the chemotaxis of neutrophils to fMLP and stimulates macrophage efferocytosis by activating AKT. NAP1051 is utilized in research on colorectal cancer.</p>

<p>Tubulin polymerization-IN-77 (Compound 15c) is a microtubule polymerization inhibitor that exhibits anti-glioblastoma activity by hindering microtubule polymerization. It demonstrates significant blood-brain barrier permeability, effectively induces G2/M phase arrest in GBM cells, and triggers apoptosis, while also markedly inhibiting tumor cell migration.</p>

<p>Terpendole E is an atypical L5 site inhibitor.</p>

<p>KU-32 is a novel and novobiocin-based Hsp90 inhibitor. It can protect against neuronal cell death.</p>

<p>JC168 is a phenyl analog of peloruside and functions as a microtubule inhibitor with antiproliferative and anticancer properties. It enhances tubulin polymerization, thereby disrupting microtubule dynamics, making it a useful agent in the study of microtubule-associated diseases.</p>

<p>APN/AKT-IN-1, a dual APN (IC50=0.21μM) &amp; AKT (IC50=0.27μM) inhibitor, hinders GSK3β phosphorylation.</p>

<p>Si306, an Src inhibitor, exhibits antitumor activity by reducing the phosphorylation of focal adhesion kinase (FAK) and the expression of epidermal growth factor receptor (EGFR), thereby inhibiting the invasion of human glioblastoma (GBM).</p>

<p>Nic-15 (compound 4n) serves as an anti-constrictive agent targeting the low vascular characteristics of pancreatic tumors. These characteristics enable cancer cells to adapt to the nutrient-deficient tumor microenvironment and develop resistance to treatment. Nic-15 modulates the PI3K/Akt/mTOR pathway and alleviates ER stress induced by Gemcitabine. It significantly inhibits migration and colony formation in MIA PaCa-2 and PANC-1 pancreatic cancer cells. When used in combination with Gemcitabine, Nic-15 effectively addresses resistance issues in pancreatic tumors. In xenograft models in vivo, Nic-15 notably enhances the efficacy of Gemcitabine.</p>

<p>Myoseverin B is a microtubule assembly inhibitor that impedes tubulin polymerization (IC50 = 2 μM) and generally exhibits low cytotoxicity across most cell types. It is utilized in antitumor agent research.</p>

<p>β-Catenin modulator-8 (Compound Ⅸa) is a specific β-catenin modulator for use in cancer research.</p>

<p>Epothilone E, a derivative of epothilone, functions by inhibiting microtubule protein activity, thereby halting cell division and exhibiting anti-tumor</p>

<p>HSP90-IN-11: potent HSP90 inhibitor, akin to AUY-922; hinders CRC/NSCLC cell proliferation; degrades EGFR, Akt proteins.</p>

<p>MKLP2-IN-1 (compound 12a) is an inhibitor of MKLP2 that demonstrates excellent oral bioactivity. In vitro, MKLP2-IN-1 inhibits the ATPase activity stimulated by recombinant MKLP2 microtubules and, in a mouse Calu-6 lung cancer model, it effectively suppresses tumor growth.</p>

<p>Tyrosine kinase-IN-9 (Compound B) is an inhibitor of c-Abl. It is useful for studying neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.</p>

<p>AM-9022 is a potent and selective KIF18A inhibitor, orally active and suitable for cancer research [1].</p>

<p>Antitubulin agents-1 disrupts microtubules, ups α-tubulin acetylation, and has anticancer properties.</p>

<p>TACC3 inhibitor 2 (Compound 13b) is a TACC3 inhibitor with an IC50 of 200 nM. It induces mitotic arrest, apoptosis (Apoptosis), and DNA damage. TACC3 inhibitor 2 is applicable for research in the field of cancer.</p>

<p>KUNG65 acts as a selective Grp94 inhibitor, demonstrating a target dissociation constant (K_d) of 540 nM. It exhibits a minimum selectivity of 73-fold compared to other Hsp90 isoforms.</p>

<p>α5β1 integrin agonist-1 is an α5β1 integrin agonist that selectively delivers 5-FU to tumour cells and induces tumour cell death.</p>

<p>Zalunfiban (RUC-4) is a potent αIIbβ3 platelet antagonist, IC50 45 nM, used in myocardial infarction research.</p>

<p>PP487 is a dual tyrosine kinase/PI(3)K inhibitor, exhibiting IC50 values of 0.017 μM, 0.072 μM, 0.004 μM, 0.01 μM, 0.55 μM, 0.22 μM, and &lt; 0.01 μM against DNA-PK, mTOR, Hck, Src, EGFR, EphB4, and PDGFR, respectively. It is applicable in cancer research [1].</p>

<p>Tasidotin hydrochloride, a dolastatin 15 analog, inhibits microtubule assembly and dynamics.</p>

<p>Icafolin-methyl is a plant-specific herbicide that acts as an inhibitor of tubulin polymerization. In plants, it metabolizes into the carboxylic acid icafolin, potentially inhibiting plant tubulin polymerization by binding to β-tubulin.</p>

<p>16,16-Dimethyl prostaglandin E2 regulates hematopoietic stem cells via EP2/EP4 and Wnt, taken orally.</p>

<p>AS2521780 is an inhibitor of PKCθ (IC50: 0.48 nM).</p>

<p>GSK3β-IN-2 (Compound S01) is an inhibitor of GSK3β with an IC50 of 0.35 nM. It activates the Wnt/β-catenin signaling pathway, promoting neurogenesis and neurite outgrowth. GSK3β-IN-2 reduces tau protein phosphorylation induced by Aβ at the Ser396 site, thereby decreasing neurofibrillary tangles. Furthermore, GSK3β-IN-2 improves Alzheimer's disease symptoms in a zebrafish model.</p>

<p>PM-060184, a tubulin polymerisation inhibitor, is used potentially for the treatment of solid tumours and breast cancer.</p>

<p>Alfalone (compound 9ia) is an antimitotic agent. It induces cleavage arrest and initiates the formation of tubercular eggs.</p>

<p>MonomethylauristatinE intermediate-17 is an intermediate compound used in the synthesis of MonomethylauristatinE. MonomethylauristatinE (MMAE) functions as a microtubule/tubulin inhibitor with anticancer properties. It is widely utilized as the cytotoxic component in antibody-drug conjugates (ADCs).</p>

<p>NRX-103094 boosts β-catenin binding to SCFβ-TrCP ligase with EC50 62 nM and Kd 0.6 nM.</p>

<p>NRX-252114 promotes mutant β-catenin degradation, binding it to E3 ligase SCFβ-TrCP (EC50: 6.5 nM; Kd: 0.4 nM).</p>

<p>AKT Kinase Inhibitor is an Akt inhibitor with antitumor activity that selectively inhibits cell proliferation in a dose-dependent manner.Cost-effective and quality-assured.</p>

<p>Ombrabulin is a derivative of CA-4 phosphate. It is known to show antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells.</p>

<p>ZW4864 is a selective inhibitor of the β-catenin/B-Cell Lymphoma 9 protein (β-catenin/BCL9 PPI) interaction, demonstrating oral activity. It inhibits β-catenin/BCL9 PPI with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM.</p>

<p>24-Methylenecycloartanyl ferulate, a compound belonging to the γ-oryzanol family, demonstrates the ability to enhance parvin-beta expression within human breast cancer cells. Furthermore, it exhibits potential as an ATP-competitive Akt1 inhibitor, with an EC 50 value of 33.3 μM.</p>

<p>Cercosporin, produced by the plant pathogen Cercospora kikuchii and the elsinochromes, is a potent photosensitizer with a short activation wavelength. Cercosporin contains perylene quinone structural features essential for PKC activity (IC50: 0.6-1.3 μM).</p>

<p>Tau tracer 2 (Pl-2620) is a specific imaging agent designed to detect and visualize Tau protein aggregates, primarily used for diagnosing neurodegenerative diseases [1].</p>

<p>20-HETE is a CYP450 product, vasoconstrictor, modulates K+ channels, affects NADPH, ROS, NF-κB, NO synthase, and cell apoptosis/proliferation.</p>

<p>Sevasemten is an allosteric inhibitor that targets skeletal muscle myosin. It displays selectivity in its inhibition, demonstrated by IC50 values of ≤10 μM for skeletal muscle myosin and &gt;100 μM for cardiac myosin, respectively.</p>

<p>PF-03814735 is a novel, potent and reversible inhibitor of Aurora A/B with IC50of 0.8 nM/5 nM, is less potent to Flt3, FAK, TrkA, and minimally active to Met and FGFR1. Phase 1.</p>

<p>CMX-2043 is a drug potentially to block oxidative damage and activate cell survival pathways.</p>

<p>Cevipabulin (TTI-237) fumarate is a microtubule-active antitumor compound and inhibits the binding of [3H] vinblastine to tubulin (IC50: 18-40 nM in the human tumor cell line).</p>

<p>BCR-ABL-IN-8 (compound 26f) is a BCR-ABL inhibitor featuring a trimethoxy group [1].</p>