Sinalização Citoesquelética

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

<p>Cemdomespib (KU-596) is a potent Hsp90 modulator with neuroprotective effects and can improve diabetic neuropathy.</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>SF0166: potent αvβ3 antagonist, IC50: 0.6 nM. Blocks cell adhesion, IC50: 7.6 pM-76 nM. Reduces neovascularization in mice.</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>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>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>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>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>KU-32 is a novel and novobiocin-based Hsp90 inhibitor. It can protect against neuronal cell death.</p>

AS2521780 is an inhibitor of PKCθ (IC50: 0.48 nM).

<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>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>KAA, an anticancer compound, inhibits centrosome clustering and targets HSET+ yeast and cancer cells.</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>Ethaboxam is a β-tubulin inhibitor and antifungal agent used against oomycete pathogens.</p>

<p>Tubulin inhibitor 19 (9b), a potent indole chalcone, strongly blocks tubulin, valuable in cancer studies.</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>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>

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

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

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

Latrunculins A is a novel marine toxin, disrupts microfilament organization in cultured cells.

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

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

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

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

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>Compound IIc inhibits tubulin polymerization, arrests cell cycle at G2/M in HCT116 cells, IC50 12.7 μM, potential for 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>Tubulin-IN-33, an oxazoloisoindole, hinders microtubule assembly; effective against NCI cancer cells.</p>

<p>Compound 13m, a difluoro derivative, activates Nrf2/HO-1, showing neuroprotective and antioxidant effects, useful in PD research.</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>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>L 734217 is an antagonist of the fibrinogen receptor.</p>

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

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

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

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

<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>

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.

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

<p>NRX-2663 boosts β-catenin binding to E3 ligase SCFβ-TrCP (Kd: 54.8 nM, EC50: 22.9 nM).</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>KY-02327 acetate inhibits Dvl-CXXC5, stabilizes Wnt/β-catenin signaling, and enhances osteoblast differentiation.</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>Tubulin polymerization-IN-32: a cancer cell growth inhibitor used for research in cancers like lymphoma.</p>

Quinagolide hydrochloride is a selective agonist of dopamine D2 receptor.

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

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

<p>Terpendole E is an atypical L5 site inhibitor.</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>TPI 287: synthetic taxane; may halt cancer by stabilizing microtubules, blocking cell division, inducing apoptosis.</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>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>NRX-252114 promotes mutant β-catenin degradation, binding it to E3 ligase SCFβ-TrCP (EC50: 6.5 nM; Kd: 0.4 nM).</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>NRX-103094 boosts β-catenin binding to SCFβ-TrCP ligase with EC50 62 nM and Kd 0.6 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>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>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>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>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>