Cytoskeletal Signaling

<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.

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>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>

G-9791 is an effective and selective inhibitor of group-I PAK.

EX05, an effective KIF18A inhibitor, exhibits an IC50 of 8.2 nM and holds potential for cancer research applications.

<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>

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

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>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>

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

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

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.

Tubulin-IN-35 inhibits oxazolylisoindole microtubule formation, targeting VL51 marginal zone lymphoma.

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

AKT-IN-11 is one of the most potent antibacterial agents against human hepatocellular carcinoma Bel-7402 cell line (IC50: 1.15 μM).

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

<p>Tubulin inhibitor 15 is a potent tubulin inhibitor with antiproliferative activity. Tubulin inhibitor 15 exhibits cytotoxicity in HepG2 cells [1].</p>

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

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

<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>

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

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-

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.

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

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

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.

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

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

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

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

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>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>

AKT-IN-10, a potent AKT inhibitor, has potential for breast and prostate cancer research, impacting cell growth and survival pathways.

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

Dictyostatin: potent microtubule stabilizer & anticancer agent with antiproliferative effects; researched for tauopathies.

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.

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.

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

<p>Tubulin polymerization-IN-32: a cancer cell growth inhibitor used for research in cancers like lymphoma.</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>AMXI-5001 hydrochloride, an oral inhibitor of PARP1/2 and microtubules, shows greater potency and selective anti-cancer effects.</p>

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

<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>