Cytoskeletal Signaling

<p>AMXI-5001 hydrochloride, an oral inhibitor of PARP1/2 and microtubules, shows greater potency and selective anti-cancer effects.</p>

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

<p>L 734217 is an antagonist of the fibrinogen receptor.</p>

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

<p>PROTACα-synuclein degrader 6 (compound T3) is a PROTAC degrader of α-synuclein and tau, with an EC50 of 1.57 μM and 4.09 μM, respectively. This compound plays a significant role in neurodegenerative disease (ND) research.</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>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>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>Terpendole E is an atypical L5 site inhibitor.</p>

<p>AMG28 is an inhibitor of Tau tubulin kinase 1 (TTBK1) and TTBK2, with IC50 values of 805 nM and 988 nM, respectively. Additionally, AMG28 suppresses the phosphorylation of tau protein at the Ser422 site, with an IC50 of 1.85 μM.</p>

<p>Tubulin polymerization-IN-32: a cancer cell growth inhibitor used for research in cancers like lymphoma.</p>

<p>Mps1-IN-8, a Mps1 inhibitor, can be utilized in the study of various tumors [1].</p>

<p>Tubulin-IN-33, an oxazoloisoindole, hinders microtubule assembly; effective against NCI cancer cells.</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>Dictyostatin: potent microtubule stabilizer &amp; anticancer agent with antiproliferative effects; researched for tauopathies.</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>AKT-IN-10, a potent AKT inhibitor, has potential for breast and prostate cancer research, impacting cell growth and survival pathways.</p>

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

<p>GSD-11: Potent, selective anti-austerity agent; blocks Akt/mTOR pathway, hinders PANC-1 cell migration &amp; colony growth. Promising for pancreatic cancer study.</p>

<p>Tubulin polymerization-IN-63 (compound 6) is an inhibitor of tubulin polymerization. It exhibits an IC50 value of 0.29 μM against MES-SA cells, making it suitable 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>KAA, an anticancer compound, inhibits centrosome clustering and targets HSET+ yeast and cancer cells.</p>

<p>FPDT combats glioblastoma by inhibiting the AKT pathway; IC50: &gt;100 μM (astrocytes), 45-68 μM (GBM cells).</p>

<p>Compound 4c: Strong tubulin inhibitor with anti-cancer &amp; anti-angiogenic effects; halts MGC-803 cells in G2/M, triggers Caspase-mediated apoptosis.</p>

<p>G-9791 is an effective and selective inhibitor of group-I PAK.</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>Compound 13m, a difluoro derivative, activates Nrf2/HO-1, showing neuroprotective and antioxidant effects, useful in PD research.</p>

<p>EV206 is an effective inhibitor of Hsp70, exhibiting antiproliferative properties. This compound induces cell apoptosis (apoptosis) and enhances the protein expression of cleaved PARP and caspase-3. Additionally, EV206 demonstrates antitumor activity.</p>

<p>HSP90α-IN-1 is an HSP90α inhibitor (IC50= 111 nM) that demonstrates anti-aging activity across various cellular senescence models. Belonging to the xanthine family, HSP90α-IN-1 is involved in research focused on combating age-related inflammation, senescence, and diseases (including cancer), and it may contribute to extending healthy lifespan.</p>

<p>Dioleyl phosphatidylserine is a phospholipid that can activate PKC-γ (Protein Kinase C-gamma) when the Ca2+ concentration is below 0.5 μM, specifically at a concentration of 100 μM.</p>

<p>FAK-IN-21 (compound 9) is a FAK inhibitor with an IC50 value of 37.52 nM. It inhibits cell growth and the phosphorylation of FAK, making it useful for research into diffuse gastric cancer.</p>

<p>Tubulin inhibitor 19 (9b), a potent indole chalcone, strongly blocks tubulin, valuable in cancer studies.</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>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>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>β-Catenin modulator-8 (Compound Ⅸa) is a specific β-catenin modulator for use in cancer research.</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>Lisavanbulin (BAL-101553) is a prodrug of Avanbulin (BAL 27862), a microtubule-targeting agent. It exhibits antitumor activity, particularly effective against tumors with high expression of end-binding protein 1.</p>

<p>Hsp90-IN-34 (compound HAM-1) is a chemical inhibitor that targets the Aha1-Hsp90 chaperone complex with high affinity (KDapp=23.5 µM). It modulates the ATPase activity of Hsp90 by affecting the interaction between Hsp90 and Aha1.</p>

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

<p>EX05, an effective KIF18A inhibitor, exhibits an IC50 of 8.2 nM and holds potential for cancer research applications.</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>AM-9022 is a potent and selective KIF18A inhibitor, orally active and suitable for cancer research [1].</p>

<p>Zalunfiban (RUC-4) is a potent αIIbβ3 platelet antagonist, IC50 45 nM, used in myocardial infarction research.</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>HSP90-IN-9: potent HSP90 inhibitor, dose-dependent fungicide, impedes biofilm/morphology with FLC, reverses FLC resistance.</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>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>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>DDO-6691 is an inhibitor of heat shock protein 90 (HSP90). It exhibits antiproliferative effects against various tumor cells, with the highest sensitivity observed in HCT-116 colon cancer cells (IC50: 1.08 μM). DDO-6691 also demonstrates potent tumor growth inhibition in HCT-116 xenograft mouse models.</p>

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

<p>Tubulin inhibitor 15 is a potent tubulin inhibitor with antiproliferative activity. Tubulin inhibitor 15 exhibits cytotoxicity in HepG2 cells [1].</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>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>Onalespib lactate is a second-generation, potent and selective HSP90 Inhibitor with antitumor activity.</p>

<p>Tasidotin hydrochloride, a dolastatin 15 analog, inhibits microtubule assembly and dynamics.</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>Wikstrol A: antifungal, anti-mitotic, anti-HIV agent with various IC50/MDC values (67.8-131 µM) and deforms P. oryzae mycelia.</p>

<p>Tubulin polymerization-IN-75 (Compound 6) is an inhibitor of tubulin polymerization, with an IC50 value of 30 μM. It effectively suppresses the proliferation of cancer cells Huh7 and 293T, demonstrating IC50 values of 14.3 μM and 13.8 μM, respectively.</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>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>RMS-07, a covalent MPS1/TTK inhibitor, has an IC50 of 13.1 nM, targeting a kinase hinge cysteine.</p>

<p>Hsp90 inhibitor</p>

<p>Tubulin polymerization-IN-74 (compound 11) is an inhibitor of tubulin polymerization, with an IC50 value of 15 μM. It is applicable to cancer research.</p>

<p>"Tubulin-IN-34 inhibits oxazolylisoindole microtubule assembly, selective for VL51 lymphoma."</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>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>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>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>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>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>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>CMX-2043 is a drug potentially to block oxidative damage and activate cell survival pathways.</p>

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