Sinalização Citoesquelética

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

<p>Antitubulin agents-1 disrupts microtubules, ups α-tubulin acetylation, and has anticancer properties.</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>PM-060184, a tubulin polymerisation inhibitor, is used potentially for the treatment of solid tumours and breast cancer.</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>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>Alfalone (compound 9ia) is an antimitotic agent. It induces cleavage arrest and initiates the formation of tubercular eggs.</p>

<p>Compound 13m, a difluoro derivative, activates Nrf2/HO-1, showing neuroprotective and antioxidant effects, useful in PD research.</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>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>NRX-2663 boosts β-catenin binding to E3 ligase SCFβ-TrCP (Kd: 54.8 nM, EC50: 22.9 nM).</p>

<p>G-9791 is an effective and selective inhibitor of group-I PAK.</p>

<p>AMXI-5001 hydrochloride, an oral inhibitor of PARP1/2 and microtubules, shows greater potency and selective anti-cancer effects.</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>TTBK1/2-IN-1 (compound 3) is a potent inhibitor of Tau tubulin kinase 1 (TTBK1) and TTBK2, with IC50 values of 816 nM and 384 nM, respectively.</p>

<p>DCEM1 binds to heat shock protein 60 (HSP60) and inhibits the interaction between HSP60 and ClpP, thereby blocking the mitochondrial unfolded protein response. Additionally, DCEM1 suppresses the expression of β-catenin and reduces ATP production in PC-3 and TKO cells. It is utilized in research related to prostate cancer.</p>

<p>Dictyostatin: potent microtubule stabilizer &amp; anticancer agent with antiproliferative effects; researched for tauopathies.</p>

<p>Uprosertib hydrochloride is a potent and selective inhibitor of pan-Akt (IC50: 180/328/38 nM for Akt1/Akt2/Akt3, respectively).</p>

<p>OXA-11 (FAK-IN-16) is a FAK inhibitor with anti-tumor activity, useful for cancer research.</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 inhibitor 19 (9b), a potent indole chalcone, strongly blocks tubulin, valuable in cancer studies.</p>

<p>Hsp90-IN-37 (Z-2) is an inhibitor of heat shock protein 90 (Hsp90), demonstrating a 69% inhibition rate on Hsp90 enzyme activity. It exhibits antitumor properties.</p>

PKCTheta-IN-2 (compound 14) is a potent and selective inhibitor of PKCθ, with an IC50 value of 0.25 nM. It demonstrates good selectivity across a broad range of kinases, including the PKC subfamily (30 kinases). Additionally, PKCTheta-IN-2 effectively inhibits the production of IL-2 in mice, where it exhibits an IC50 of 682 nM.

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

<p>"Tubulin-IN-34 inhibits oxazolylisoindole microtubule assembly, selective for VL51 lymphoma."</p>

<p>Latrunculins A is a novel marine toxin, disrupts microfilament organization in cultured cells.</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>Hsp90 inhibitor</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>Onalespib lactate is a second-generation, potent and selective HSP90 Inhibitor with antitumor activity.</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>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>XD23 is a potent osteosarcoma inhibitor that functions by downregulating DKK1 and activating the WNT/β-catenin signaling pathway.</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>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>16,16-Dimethyl prostaglandin E2 regulates hematopoietic stem cells via EP2/EP4 and Wnt, taken orally.</p>

<p>GR 83895 is an antagonist of prototype fibrinogen receptor.</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>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>ZLY06 is a dual agonist of peroxisome proliferator-activated receptors (PPAR) δ and γ with oral activity (PPAR δ: EC50=341 nM; PPARγ: EC50=237 nM). It mediates the upregulation of CD36 and induces hepatic lipid accumulation by inhibiting the phosphorylation of AKT1. Moreover, ZLY06 significantly improves glucose and lipid metabolism without increasing body weight, primarily by enhancing the β-oxidation of fatty acids and reducing hepatic lipid synthesis, thereby alleviating fatty liver disease.</p>

<p>HSP90-IN-32, a carboxy-terminus inhibitor of Hsp90C, exhibits antiproliferative activity in various cell lines including SKMel173, SKMel103, SKMel19, and A375, with IC50 values of 1.01 μM, 0.782 μM, 0.607 μM, and 1.413 μM, respectively. This compound holds potential for research in anticancer agents.</p>

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

<p>Tubulin inhibitor 16 is a potent tubulin inhibitor with antiproliferative activity. Tubulin inhibitor 16 exhibits cytotoxicity in HepG2 cells [1].</p>

<p>FAK inhibitor7, a potent FAK inhibitor, demonstrates an IC50 of 3.58 nM. This compound effectively inhibits downstream signaling cascades of FAK (such as Src and AKT), which leads to cell cycle arrest at the G0/G1 phase and induces cytotoxic autophagy in ovarian cancer cells. Additionally, FAK inhibitor7 has been shown to suppress tumor metastasis and growth in ovarian cancer mouse models.</p>

<p>PI3K-IN-29: Strong PI3K block, inhibits Akt phosphorylation. IC50: U87MG 0.264µM, HeLa 2.04µM, HL60 1.14µM.</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>L 734217 is an antagonist of the fibrinogen receptor.</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>HG-7-86-01 is a selective type II tyrosine kinase inhibitor with antiproliferative activity against mutant T315I- Bcr-Abl for chronic myeloid leukemia (CML).</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>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>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>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>Compound IIc inhibits tubulin polymerization, arrests cell cycle at G2/M in HCT116 cells, IC50 12.7 μM, potential for cancer research.</p>

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

<p>Tubulin polymerization-IN-32: a cancer cell growth inhibitor used for research in cancers like lymphoma.</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>EX05, an effective KIF18A inhibitor, exhibits an IC50 of 8.2 nM and holds potential for cancer research applications.</p>

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